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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">In November 2019&#44; some severe pneumonia cases were reported in Wuhan&#44; China&#46; In December 2019&#44; the rapid increase in the number of these cases with an epidemiological association with the local market caught the attention of Chinese health authorities&#46; The cause of these outbreaks was identified in January 2020 as a coronavirus&#59; the World Health Organization &#40;WHO&#41; later called the virus severe acute respiratory syndrome coronavirus 2 &#40;SARS-CoV-2&#41; and the disease caused by it coronavirus disease &#40;COVID-19&#41;&#46; The disease quickly spread to other countries&#44; which led the WHO to declare an international public health emergency on January 30&#44; 2020 and a pandemic on March 1&#44; 2020&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">SARS-CoV-2 exerts a pathogenic mechanism by binding the spike protein on its surface to the type 2 angiotensin-converting enzyme &#40;ACE2&#41; receptor&#44; whose physiological action is to act as a regulatory mechanism against the effects of angiotensin&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> ACE2 receptors are significantly expressed in the lung&#44; mainly in type II pneumocytes&#44; the predominant site of the pathogenicity of the virus in the human body&#44; as well as in other organs such as the heart&#44; vascular endothelium&#44; intestinal epithelium&#44; and kidneys&#44; thus providing a favorable mechanism for multiple organ dysfunction&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The literature is consistent in stating that COVID-19&#44; a disease caused by SARS-CoV-2&#44; affects children more rarely and mildly than it affects adults&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> Some of the hypotheses that explain this phenomenon include differences in ACE2 receptor expression&#44; differences in the immune system &#40;better innate immune response in children&#44; especially when compared with the elderly&#44; and a lesser pro-inflammatory response with less cytokine production&#41;&#44; a lower prevalence of comorbidities&#44; lower exposure to the pathogen in the initial phase of the pandemic&#44; respiratory infections by other coronaviruses that are already circulating in the community&#44; greater colonization by other viruses and bacteria conferring interactions with the microbiota and competition&#44; and a greater risk of children being infected by the second or third generation of SARS-CoV-2&#44; a phenomenon that is generally associated with reduced aggressiveness&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Although COVID-19 is less severe and less frequent in children&#44; as the pandemic progresses&#44; there are reports of a worrying clinical picture in the pediatric age group&#44; with symptoms similar to Kawasaki disease and toxic shock that require assertive conduct by pediatricians&#44; especially those working in emergency services&#46; Similar reports have been reported in several countries under the name &#8220;multisystem inflammatory syndrome in children&#8221; &#40;MIS-C&#41; temporarily associated with COVID-19&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#8211;13</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The pathophysiology of MIS-C is unclear&#44; but it appears to be a consequence of an exacerbated immune system response or maladaptive response of the host&#46; After the virus enters the human cells&#44; the first line of defense against infection should be a quick and well-coordinated immune response&#59; however&#44; when this mechanism is unregulated and excessive&#44; hyperinflammation can occur&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Cytokines that play an important role in inducing immunity and immunopathology during infections in excess can cause the clinical syndrome known as cytokine storm&#46; The inflammatory response caused by SARS-CoV-2 appears to be the major cause of mortality in infected patients&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> The infection of dendritic cells or macrophages by SARS-CoV-2 induces the production of low levels of antiviral cytokines and increases the production of inflammatory cytokines &#40;tumor necrosis factor &#91;TNF&#93;&#44; interleukin &#91;IL&#93;-1&#44; IL-6&#44; and interferon-&#947;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#8211;19</span></a> An apparent action of inflammatory cytokines&#44; especially IL-6&#44; is the expression of tissue factor&#44; which leads to the activation of coagulation and the complement cascade and the release of inflammatory kinins<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> In addition&#44; the excessive production of IL-6&#44; IL-10&#44; and TNF is negatively correlated with the total number of lymphocytes affecting both innate and acquired immunity&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The massive release of inflammatory mediators with exaggerated activation of the immune system is similar to the syndrome known as cytokine storm&#44; which occurs in a group of conditions that share the same pathogenic mechanism but have different triggering factors&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> The neutrophil&#44; the main protagonist of the cytokine storm&#44; has the capacity to secrete ferritin&#44; which explains the high levels found in several inflammatory syndromes&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Ferritin&#44; in turn&#44; has an immunosuppressive action and inhibits the differentiation of myeloid cells and T and B lymphocytes&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> worsening the host&#39;s responsiveness&#46; High levels of ferritin and hemophagocytosis are related to inflammation severity and are present in several diseases with different etiologies&#58; macrophage activation syndrome&#44; hemophagocytic lymphohistiocytosis &#40;HLH&#41;&#44; sepsis&#44; multisystem inflammatory syndrome &#40;MIS&#41;&#44; staphylococcal toxic shock&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> and severe cases of COVID-19&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> suggesting that these are different phenotypes of the same inflammatory process&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Thus&#44; MIS-C appears to be a clinical syndrome that shares aspects with other inflammatory conditions in which large amounts of cytokines cause the dysfunction of several organs&#44; including Kawasaki disease&#44; sepsis&#44; macrophage activation syndrome&#44; and secondary HLH &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Its action on the vascular bed is very important&#44; causing hypotension and the leakage of fluids and immune system cells in the lung&#44; heart&#44; and other organs&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Cardiac involvement&#44; whether myocardial dysfunction&#44; pericarditis&#44; valve dysfunction&#44; or coronary abnormalities&#44; is noteworthy&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">The criteria for the clinical diagnosis of MIS-C&#44; according to the Royal College of Paediatrics and Child Health &#40;RCPCH&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> are shared by other inflammatory diseases &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Notably&#44; fever&#44; adenomegaly&#44; rash&#44; involvement of the mucous membranes&#44; edema of the hands and feet&#44; and involvement of the coronary arteries are clinical criteria for the diagnosis of Kawasaki disease&#46; The presence of fever and coronary abnormalities are symptoms of Kawasaki-like disease&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> which explains the connection to MIS-C associated with COVID-19&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">The laboratory criteria of MIS-C &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41; also include symptoms that overlap with HLH&#44; such as elevated triglycerides and ferritin and the involvement of two hematological series&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> HLH&#44; primary or secondary to infection&#44; is a complex clinical syndrome characterized by an excessive but ineffective inflammatory response&#44; intense macrophage activation&#44; tissue invasion by T lymphocytes&#44; and the secretion of large amounts of cytokines&#44; possibly due to the stimulation of Toll-like receptors&#46; The ability of SARS-CoV-2 to bind to these receptors justifies the presence of common laboratory parameters for COVID-19 and HLH&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Studies are needed to better understand MIS-C&#46; The challenges are related to the pathophysiological mechanisms&#44; diagnostic criteria&#44; and treatment strategies&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> The disease is rare&#44; affecting 2 in 100&#44;000 children under 21 years of age&#44; and it has a temporal relationship with COVID-19&#44; appearing two to four weeks after SARS-CoV-2 infection&#46; The initial approach to managing pediatric patients with suspected MIS most often occurs in the emergency department&#44; which requires that professionals working in this area&#44; especially pediatricians&#44; be prepared&#46; This review aims to contribute to this preparation&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Clinical presentation</span><p id="par0060" class="elsevierStylePara elsevierViewall">There is limited knowledge regarding SARS-CoV-2 infection in children&#46; The clinical picture is oligosymptomatic when compared with most adult patients<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a>&#59; most symptoms are those of upper respiratory tract infection and mild pneumonia<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> with some reports of gastrointestinal symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> However&#44; some publications &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41; recently reported acute and severe clinical manifestations in children and adolescents&#44; with an evolution to cardiogenic shock and the need for intensive care &#40;<a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">At the end of April 2020&#44; the United Kingdom issued an alert regarding the growing number of pediatric patients who had a clinical picture compatible with toxic shock&#44; signs similar to Kawasaki disease&#44; changes in hemodynamic parameters&#44; and gastrointestinal manifestations&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Evolution with cardiogenic shock&#44; the need for ventilatory support and vasoactive drugs&#44; coronary dilation&#44; and elevated inflammatory test results without evidence of pulmonary involvement were observed in eight patients with the initial picture of high fever&#44; skin rash&#44; non-purulent conjunctivitis&#44; abdominal pain&#44; and diarrhea&#46; One patient died&#46; SARS-CoV-2 positivity was identified through the investigation of viral RNA in two patients and adenovirus in another&#59; in others&#44; there was a history of contact with first-degree relatives with COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">A study of 14 pediatric intensive care units in France and Switzerland reported 35 children who developed severe cardiac decompensation with signs of MIS-C associated with COVID-19&#46; The laboratory diagnosis was made by polymerase chain reaction &#40;PCR&#41; detection in a nasopharyngeal swab and&#47;or positive serology in 31 of the 35 patients&#46; In this case series&#44; the clinical manifestations at admission were fever&#44; asthenia&#44; and gastrointestinal symptoms such as abdominal pain&#44; diarrhea&#44; and vomiting in 80&#37; of patients&#46; Some signs suggestive of Kawasaki disease&#44; such as skin rash&#44; cervical adenopathy&#44; cheilitis&#44; and meningism&#44; were also observed&#44; without meeting all classic clinical criteria of the disease&#46; The main laboratory findings revealed changes in inflammatory tests &#40;PCR&#44; erythrocyte sedimentation rate&#44; brain natriuretic peptide &#91;BNP&#93;&#44; interleukin-6&#44; D-dimer&#44; troponin I&#41; and on echocardiography&#44; with a relevant reduction in ejection fraction and left ventricular hypokinesia in most patients&#46; All patients required intensive care unit &#40;ICU&#41; admission&#44; 80&#37; used inotropic drugs&#44; 28&#37; used extracorporeal membrane oxygenation &#40;ECMO&#41; and two-thirds required mechanical ventilation&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> The improvement in myocardial dysfunction observed in this series suggests that the mechanism of heart failure may be more closely associated with the inflammatory process&#44; leading to the distention of myocardial fibers and activation of BNP rather than to the direct lesions of the virus&#46; Another noteworthy observation is that the disease occurred in an older age group compared to that usually affected by Kawasaki disease&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The New York State database on MIS-C has similarities with the European series&#46; On July 3&#44; 2020&#44; 230 cases had been reported with a total of two deaths&#46; The most prevalent symptoms are prolonged fever &#40;for more than five days&#41;&#44; abdominal pain&#44; diarrhea&#44; vomiting&#44; dyspnea or tachypnea&#44; paleness or cyanosis of extremities&#44; decreased urine output&#44; and lethargy or mental confusion&#46; Positive antigenic or serological tests for SARS-CoV-2 were observed in 94&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Two studies from the US<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37&#44;38</span></a> presented the largest case series related to MIS-C&#46; Using the same New York database&#44; Dufort EM et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> published a study of 191 patients&#44; among whom 95 had confirmed MIS-C and four had suspected MIS-C&#46; Regarding the definition of confirmed cases&#44; clinical criteria&#44; laboratory criteria &#40;alteration of at least two exams&#41;&#44; and serological evidence or molecular testing &#40;RT-PCR&#41; for SARS-CoV-2 were used&#46; Suspected cases were classified according to the clinical condition and epidemiological criteria&#46; All patients had fever&#44; 97&#37; had tachycardia&#44; 80&#37; had gastrointestinal symptoms&#44; 60&#37; had rash&#44; 57&#37; had conjunctivitis&#44; and 27&#37; had mucosal changes&#46; In this study&#44; some symptoms little described by other authors stand out&#44; such as hepatomegaly&#44; splenomegaly&#44; ascites&#44; inflammation&#44; and enlargement of the cecal appendix and gallbladder&#46; In addition&#44; it is evident that skin manifestations are common in children under 5 years of age&#44; and cases of myocarditis or cardiogenic shock are predominant in adolescents&#46; The authors also highlighted the presence of neurological symptoms in 13&#37; of children and 38&#37; of adolescents&#46; Dufort EM<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> and other authors emphasized the presence of encephalopathy&#44; headache&#44; signs of cerebellar alteration&#44; muscle weakness&#44; and reduced reflexes&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">A study of 186 patients across the United States reinforced the clinical and laboratory worsening&#44; mainly among patients over 10 years of age&#44; with inflammatory markers and cardiac enzymes with more significant changes&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">A study in Bergamo&#44; Italy&#44; compared a group of children with Kawasaki-like disease diagnosed before the COVID-19 pandemic with a group diagnosed during the pandemic&#46; In the latter&#44; an increase in the number of cases was observed by up to 30 times&#44; with more pronounced cardiac alterations&#44; a higher frequency of macrophage activation syndrome&#44; and&#44; as in reports from Europe&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> a predominance of older children affected&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">A UK publication described 58 children from eight ICU facilities with the clinical and laboratory criteria for MIS-C associated with COVID-19 caused by SARS-CoV-2 in 2020&#46; The mean age was 9 years&#44; and fever occurred in 100&#37; of cases&#44; vomiting in 45&#37;&#44; abdominal pain in 53&#37;&#44; diarrhea in 52&#37;&#44; and conjunctivitis in 45&#37;&#46; Shock due to myocardial dysfunction was observed in 50&#37; of the patients&#59; of those&#44; 79&#37; required mechanical ventilation and the use of inotropic drugs&#46; There was evidence of SARS-CoV-2 infection &#40;by serology and&#47;or reverse transcription-PCR &#91;RT-PCR&#93;&#41; in 78&#37; of the total patient group&#46; The authors compared the findings of these patients with those hospitalized from 2002 to 2019&#44; diagnosed with Kawasaki&#44; shock&#44; and toxic shock syndrome&#44; and observed older age &#40;9 years versus 2&#46;7 years&#41; and inflammatory tests with elevated levels&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> This corroborates the observation that the inflammatory state compatible with MIS-C associated with COVID-19 has a peculiar presentation&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Studies from Germany&#44; Austria&#44; and Portugal have also reported severe cases with gastrointestinal symptoms and increased inflammatory cytokines with an evolution compatible with Kawasaki-like or toxic shock syndrome associated with the detection of SARS-CoV-2 by RT-PCR or serology&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">No MIS-C case reports from China&#44; Japan&#44; or South Korea were retrieved&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> The multiple cases reported in the literature have led the WHO&#44; the US Centers for Disease Control and Prevention&#44; and the RCPCH to publish similar definitions of possible cases eligible for MIS-C &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;29</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">It is important to note that the period of MIS-C development after SARS-CoV-2 infection remains a matter of debate&#46; The disease can develop between the first and the second week after infection with the virus<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>&#59; however&#44; in patients with negative RT-PCR and serology test results&#44; the evolution to MIS-C can be considered within six weeks after patient exposure to COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Laboratory and imaging tests</span><p id="par0115" class="elsevierStylePara elsevierViewall">Complementary tests&#44; an integral part of the diagnostic criteria&#44; are not always available&#44; which can lead to diagnostic difficulties and treatment delays&#46; It is important for the pediatrician to raise the clinical suspicion and&#44; in the face of scarce resources&#44; arrange for referral to a more equipped emergency service&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Real time RT-PCR<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">43&#44;44</span></a> is the most recommended method for identifying SARS-CoV-2&#44; and the ideal period for its collection is between the fifth and sixth symptomatic day &#40;range&#58; third to seventh day&#41;&#46; If the sample is collected before the third day of illness and the result is negative&#44; a new collection is recommended on the third day&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Seroconversion is believed to occur after the seventh day of illness in 50&#37; of patients and in 14 days in all patients&#46; It is more relevant for epidemiological studies and can assist in COVID-19 diagnosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">43&#44;45</span></a> The possibility of cross-reactions leading to false-positive results in negative serum has not been ruled out&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">In observational studies of patients who developed MIS-C&#44; the probability of identifying SARS-CoV-2 infection by serology was two to three times higher than that by RT-PCR&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a> These findings are expected&#44; since MIS-C is a late form of the disease that occurs when the presence of the virus is no longer expected and the antibody rates are on the rise&#46; This makes serology particularly useful in correlating SARS-CoV-2 and MIS-C&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Inflammatory markers of organic function</span><p id="par0135" class="elsevierStylePara elsevierViewall">Considering that MIS-C is a late manifestation of COVID-19&#44; laboratory findings observed in the infectious phase of the disease maintain some diagnostic relevance even in the late inflammatory phase and may change&#44; significantly or not&#44; as the condition worsens &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Despite the lack of an absolute consensus&#44; most authors accept that disease deterioration changes blood count and inflammatory test results&#44; impairs liver and renal function &#40;hyperbilirubinemia&#44; hypertriglyceridemia&#44; and hypoalbuminemia&#41;&#44; changes coagulation&#44; changes myocardial enzymes&#44; and elevates kinins&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">The aspects that alert to MIS-C point to the presence&#44; although not always&#44; of one or more changes in inflammatory test results&#44; such as&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0150" class="elsevierStylePara elsevierViewall">Elevation of C-reactive protein &#40;CRP&#41;&#44; erythrocyte sedimentation rate&#44; procalcitonin&#44; D-dimer&#44; ferritin&#44; lactic dehydrogenase&#44; fibrinogen&#44; IL-6&#44; or neutrophils&#59; and</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0155" class="elsevierStylePara elsevierViewall">Reduction of lymphocytes and&#47;or albumin&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#44;49&#44;50</span></a></p></li></ul></p><p id="par0160" class="elsevierStylePara elsevierViewall">Feldstein et al&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> in a study published at the end of June 2020&#44; noticed that among the multiple tests performed on patients affected by MIS-C&#44; at least four were altered&#44; primarily increased CRP&#44; lymphopenia&#44; neutrophilia&#44; increased ferritin&#44; hypoalbuminemia&#44; and myocardial dysfunction&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Verdoni et al&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> when observing children and young people diagnosed with Kawasaki-like disease who developed coronary artery aneurysm in the pre- and post-SARS-CoV-2 era&#44; noticed a tendency toward inflammation and more pronounced cardiac injury markers in which CRP&#44; troponin&#44; ferritin&#44; and BNP were proven useful as predictors of disease worsening&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> In the same line of investigation&#44; Riphagen et al&#46; highlighted that patients who had elevated cardiac enzymes also had non-specific changes on electrocardiography &#40;ECG&#41; and echocardiography&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a> Whittaker et al&#46; warned of the recommendation to investigate these patients using echocardiography&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Imaging tests&#44; including ultrasound&#44; chest X-ray&#44; and chest tomography</span><p id="par0170" class="elsevierStylePara elsevierViewall">Pulmonary involvement in MIS-C is generally mild or non-existent&#46; Imaging tests are indicated for patients who have respiratory symptoms &#40;tachypnea&#44; dyspnea&#44; and&#47;or hypoxemia&#41;&#46; In this situation&#44; if available&#44; bedside ultrasound &#40;point of care ultrasound&#41; is preferable over others since it provides information comparable to chest tomography with the advantages of avoiding ionizing exposure and displacement of the patient&#44; allowing simultaneous assessment of the clinical and imaging information&#44; and reducing the risks of contamination of employees&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">On a progressive scale of worsening&#44; the most frequent ultrasound findings are irregular pleura&#44; B lines&#44; small pleural consolidations&#44; involvement of the upper and anterior areas&#44; consolidation&#44; air bronchography&#44; and pleural effusion&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Echocardiography and ECG</span><p id="par0180" class="elsevierStylePara elsevierViewall">Echocardiography and ECG are of fundamental relevance in MIS-C&#44; since myocardial and coronary involvement are critical points of unfavorable outcomes&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">The most significant findings of a review<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> of cardiac changes in COVID-19 were&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0190" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">ECG</span>&#58; Various aspects that mimic acute coronary syndrome&#44; non-specific changes in the ST segment&#44; an altered or inverted T wave&#44; or elevation or depression of PR or ST as a result of myocardial inflammation &#40;indicative of severity and worse prognosis&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0195" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Echocardiography</span>&#58; Dysfunction&#44; hypocontractility&#44; or even segmental absence of contractility in the myocardial chambers&#46; In this case&#44; alterations indicated severity and worse prognosis&#46;</p></li></ul></p><p id="par0200" class="elsevierStylePara elsevierViewall">In a prospective observational study of 21 children and young people with MIS-C&#44; pericardial effusion &#40;48&#37;&#41;&#44; pleural effusion &#40;14&#37;&#41;&#44; myocarditis &#40;76&#37;&#41; with a moderate to severe drop in left ventricular ejection fraction &#40;from 57&#37; to 10&#37;&#41;&#44; and coronary abnormalities &#40;38&#37;&#41;&#44; such as more pronounced brilliance or dilation without the identification of an aneurysm&#44; were observed&#46; Analyzing the ECG tracings&#44; the authors identified prolonged QT interval&#44; occasional ventricular arrhythmias&#44; and diffuse ST elevation&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Myocardial impairment has been found in autopsies of adults&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> In the English literature&#44; no articles correlating anatomopathological findings and disease caused by SARS-CoV-2 in childhood were retrieved&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> describes the laboratory and imaging findings according to COVID-19 progression &#40;mild&#44; moderate&#44; or severe and MIS-C&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Treatment</span><p id="par0215" class="elsevierStylePara elsevierViewall">MIS-C temporarily associated with COVID-19 is a rare but serious and potentially fatal presentation&#59; thus&#44; as in any condition where life is at risk&#44; there must be an emphasis on supportive treatment that includes oxygen supplementation&#59; ventilatory&#44; cardiovascular&#44; and renal support&#59; and pharmacotherapy in cases in which it is indicated&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> Supportive treatment does not differ from other situations and will not be outlined here&#44; as there are established pediatric guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Antibiotic administration cannot be delayed due to the possibility of toxic shock syndrome&#46; It is also important to highlight the team&#39;s mandatory use of personal protective equipment from the start of treatment&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Information regarding the indication and appropriate timing of potential treatments is limited&#44; and several centers consider the use of intravenous immunoglobulin &#40;IVIG&#41;&#44; corticosteroids&#44; immunomodulators&#44; anticoagulants&#44; and antiplatelet agents&#46; The selection of two or more immunomodulators to control the inflammatory condition has been described by several authors&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37&#44;38&#44;41&#44;60&#44;63</span></a> Patients with Kawasaki-like conditions who are classified as high risk for immunoglobulin resistance have been receiving a combination of IVIG with corticosteroids&#44; as this treatment appears to reduce the prevalence of coronary abnormalities and duration of fever&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;36</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">In addition to IVIG&#44; other potential strategies have been suggested to treat the cytokine storm&#46; The transfer of knowledge from the cytokine storm in the context of autoimmune and infectious diseases to a new viral disease is complex and challenging&#46; Evidence of hyperinflammation reinforces the therapeutic possibility of using immunomodulatory agents in COVID-19<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;56</span></a>&#59; in this scenario&#44; therapy with IVIG&#44; corticosteroids&#44; selective cytokine blockers &#40;anakinra&#44; tocilizumab&#41;&#44; anticoagulants&#44; remdesivir&#44; and convalescent plasma can reduce the inflammatory response and mortality&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">The use of medications is justified by the severity of the situation and the effectiveness in similar clinical conditions&#44; although the effectiveness in MIS-C has yet to be proven&#46; Evidence regarding each of these therapeutic modalities is provided in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Intravenous human immunoglobulin</span><p id="par0240" class="elsevierStylePara elsevierViewall">In addition to life support treatment&#44; IVIG is the predominant therapeutic option for MIS-C in different centers when Kawasaki disease is part of the differential diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> The RCPCH proposes that mild or moderate cases of MIS-C associated with COVID-19 be treated with supportive therapy&#44; that severe cases be admitted to the ICU&#44; and that the prescription of immunomodulators should be discussed with physicians who have experience using this type of medication&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Thus&#44; specialists such as infectologists&#44; rheumatologists&#44; immunologists&#44; or hematologists must be involved in the emergency treatment of MIS-C&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">The US National Institutes of Health reinforces a similar concept&#44; recognizing that there is limited information regarding the treatment of MIS-C associated with COVID-19&#44; and stating that supportive therapy is essential&#59; however&#44; many centers consider using IVIG&#44; corticosteroids&#44; and other immunomodulators&#44; although definitive data are not available&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">Most patients included in the MIS-C case series with a differential diagnosis of atypical Kawasaki or Kawasaki-like disease received IVIG &#40;2<span class="elsevierStyleHsp" style=""></span>g&#47;kg&#41;&#44; with frequent admission to the ICU and evolution with shock and myocardial dysfunction requiring vasoactive support&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">40&#44;47&#44;58&#8211;60</span></a> Case reports of COVID-19 and Kawasaki-like disease also suggested IVIG as therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">61</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">Siddiqi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a> proposed the use of immunomodulatory agents as therapeutic options in adults in the COVID-19 stage characterized by a state of hyperinflammation before multisystem organic damage occurs&#46; At this stage&#44; corticosteroids may be justified with or without the use of cytokine inhibitors or IVIG&#46; In general&#44; the prognosis and recovery of this critical stage of the disease are poor&#59; thus&#44; its rapid recognition and treatment are essential for a better evolution&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Belhadjer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> described a case series of 35 children admitted to the ICU diagnosed with MIS-C&#44; all of whom had myocardial dysfunction and 80&#37; of whom required hemodynamic support with inotropic agents&#46; Twenty-five patients received IVIG therapy and recovered myocardial function&#44; thus showing an association between IVIG use and good prognosis&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Miller et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a> reported on 44 patients with MIS-C and gastrointestinal symptoms&#59; among them&#44; none needed hemodynamic support and 81&#37; received IVIG&#46; The severity of the clinical presentation is common in the reports of MIS-C case series and deserves attention due to the high rate of patients requiring ICU admission and the high proportion of children with myocardial dysfunction&#44; cardiogenic shock&#44; and the need for vasoactive support&#46; Most of these patients received IVIG treatment and recovered myocardial function&#59; the evolution to death was an exception&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;41&#44;51&#44;60&#44;64</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">Dufort et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> reported on 99 children in New York State under 20 years of age who were diagnosed with MIS-C&#59; of them&#44; 70&#37; received IVIG&#46; It is noteworthy that the two children among them who died did not receive immunomodulatory treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> Another study of 26 states in the United States described 186 children and adolescents with fever for at least 24<span class="elsevierStyleHsp" style=""></span>hours&#44; multisystem involvement&#44; laboratory evidence of inflammation&#44; and SARS-CoV-2 infection&#46; IVIG treatment was used in 77&#37; of these patients&#59; 21&#37; received a second dose&#46; The authors propose that the choice of treatment should be based on the mechanisms of aggression&#44; <span class="elsevierStyleItalic">i&#46;e&#46;</span>&#44; active viral replication in the affected tissues&#44; the host&#39;s exuberant inflammatory response&#44; or both&#46; Antiviral agents are beneficial in the first situation&#44; whereas immunomodulatory agents are preferred in cases of immune dysregulation&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">The mechanism of action of IVIG is unknown in Kawasaki disease or in MIS-C associated with COVID-19&#46; It is likely associated with the global anti-inflammatory effect&#44; with modulation in the production of cytokines&#44; neutralization of toxins and other pathogens&#44; and increased regulatory activity of T cells&#44; among others&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;65</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Corticosteroids</span><p id="par0280" class="elsevierStylePara elsevierViewall">The use of corticosteroids in patients with SARS and Middle East respiratory syndrome &#40;recent coronavirus epidemics&#41; has not shown any influence on mortality in addition to increasing viral load and delaying viral clearing&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">66&#44;67</span></a> Furthermore&#44; the current WHO guideline does not recommend the universal use of corticosteroids in the treatment of severe COVID-19&#44; unless there was some other clinical condition in which the medication had a proven therapeutic effect&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> Immunosuppression can be beneficial in cases of hyperinflammatory states&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Although a randomized study using dexamethasone in adults reported an association between its use and a significant reduction in mortality&#44; these results cannot yet be applied to the pediatric age group&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">A meta-analysis of 2&#44;746 patients with Kawasaki disease demonstrated that the association of corticosteroids and immunoglobulin is related to a reduced risk of coronary aneurysm compared to isolated IVIG therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">68</span></a> The European consensus of Kawasaki disease recommends the use of corticosteroids in some conditions&#44; such as resistance to IVIG&#44; presentation as HLH&#44; presence of shock&#44; evidence of coronary and or peripheral aneurysms&#44; age less than 1 year&#44; and Kobayashi score &#8805;4&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">69</span></a> The suggested corticosteroid regimen is methylprednisolone 1&#46;6&#8211;2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day for 5&#8211;7 days or methylprednisolone 30<span class="elsevierStyleHsp" style=""></span>mg&#47;day for 3 days&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall">Corticosteroids &#40;methylprednisolone and hydrocortisone&#41; correspond to a treatment modality most used in MIS-C according to publications of pediatric case series as shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;34&#44;35&#44;40&#44;41&#44;47&#44;57&#44;58&#44;61</span></a> In most studies&#44; the dose of methylprednisolone was 2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg and the duration of therapy was not well defined&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">There is much doubt regarding the efficacy and safety of using corticosteroids in COVID-19&#44; and clinical studies are needed in all age groups&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">IL-6 inhibitors</span><p id="par0300" class="elsevierStylePara elsevierViewall">Tocilizumab is a recombinant monoclonal antibody that binds directly to the IL-6 receptor&#44; which&#44; in addition to crossing the blood&#8211;brain barrier and releasing prostaglandin E2&#44; triggers the increase in temperature&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> The inhibition of IL-6 receptors promotes a reduction in cytokine production&#44; thus configuring some indication of possible treatment for hyperinflammation&#44; although there are no studies in pediatric populations&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">Otocilizumab is indicated in adult patients with autoimmune diseases and is approved by the US Food and Drug Administration &#40;FDA&#41; for use in cytokine release syndrome in critical cases in adults and children&#46; Due to the similarities between the cytokine release syndrome and the cytokine storm in COVID-19&#44; studies are underway to evaluate the safety and efficacy of this therapeutic modality&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a></p><p id="par0310" class="elsevierStylePara elsevierViewall">Siltuximab&#44; another monoclonal antibody&#44; binds directly to IL-6 and can be considered a second-line treatment for COVID-19 cases resistant to tocilizumab&#44; although there is no evidence of its effectiveness to date&#46;</p><p id="par0315" class="elsevierStylePara elsevierViewall">Data are lacking in the pediatric age group to recommend or contraindicate the use of IL-6 inhibitors&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">IL-1 inhibitors</span><p id="par0320" class="elsevierStylePara elsevierViewall">The use of anakinra&#44; a recombinant IL-1 receptor antagonist&#44; has been suggested for modulating the effects of cytokines&#46; A randomized study in adult sepsis patients reported increased survival in patients with hyperinflammation who received anakinra without increasing adverse effects&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">70</span></a> Although there is no evidence of a correlation between serum IL-1 levels and COVID-19 severity&#44; ongoing multicenter studies have evaluated the role of anakinra associated with emapalumab in reducing hyperinflammation in patients with severe SARS-CoV-2 infection&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">Anakinra was used as additional therapy in MIS-C in 18&#46;2&#37; of cases in the American series<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a> and in 5&#37; of cases in the United Kingdom&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> and can be considered in the treatment of MIS-C that is refractory to IVIG and corticosteroids&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">71</span></a> The research field remains open&#44; as its role in this situation cannot be properly assessed&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">TNF inhibitors &#40;infliximab&#41;</span><p id="par0330" class="elsevierStylePara elsevierViewall">TNF is one among the factors that trigger the cytokine storm&#59; therefore&#44; its role in the treatment of SARS-CoV-2 infection deserves investigation&#46; A meta-analysis using anti-TNF showed improved survival in patients with sepsis&#44; a situation in which the role of cytokines is also relevant&#44;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">72</span></a> thus opening a therapeutic possibility in severe cases of COVID-19&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Medications with antiviral activity</span><p id="par0335" class="elsevierStylePara elsevierViewall">Remdesivir shows <span class="elsevierStyleItalic">in vitro</span> and <span class="elsevierStyleItalic">in vivo</span> activity against SARS-CoV-2 and other beta-coronaviruses&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">73</span></a> A multicenter randomized placebo-controlled study with adult patients hospitalized with COVID-19 pulmonary infection observed that the use of remdesivir decreased the length of hospital stay&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">74</span></a> The FDA has issued emergency use authorization for remdesivir for the treatment of severe COVID-19 in adults and children&#46; In Brazil&#44; remdesivir was not available at the time of this publication&#46;</p><p id="par0340" class="elsevierStylePara elsevierViewall">Other antivirals have been tested in adults with severe COVID-19&#46; The combination of lopinavir and ritonavir was used in a cohort of adult patients hospitalized with severe SARS-CoV-2 pneumonia with no evidence of superior results to those of standard treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">75</span></a> No studies with these medications in COVID-19 in children were retrieved&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Acetylsalicylic acid</span><p id="par0345" class="elsevierStylePara elsevierViewall">There are reports of use of acetylsalicylic acid &#40;ASA&#41; in cases of MIS-C in situations that meet Kawasaki-like criteria&#46; Since exacerbated inflammation is associated with organ damage and coronary aneurysm&#44; the anti-inflammatory action of ASA at a dose of 30&#8211;50<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day can be useful&#44; although there is no reliable evidence that a reduction in the rate of coronary abnormalities occurs in Kawasaki disease&#46; The antiplatelet action of ASA at a dose of 3&#8211;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day is indicated 48<span class="elsevierStyleHsp" style=""></span>h after fever defervescence and should be maintained for 6-8 weeks in cases where there are no coronary changes&#46; Some authors have suggested the use of continuous ASA in patients with coronary abnormalities to prevent thrombosis&#46; It is important to highlight that bleeding is a contraindication to ASA use and that care should be taken in the presence of thrombocytopenia and renal dysfunction&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;69</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Anticoagulation</span><p id="par0350" class="elsevierStylePara elsevierViewall">Anticoagulant therapy in pediatrics was mainly derived from studies in adults&#46; Cytokine storm causes activation of the coagulation cascade&#44; resulting in thrombosis&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;26</span></a> in addition to evidence of severe vascular injury in severe COVID-19&#46;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">76&#44;77</span></a> Autopsy findings confirm the state of hypercoagulability and extensive endothelial injury through the observation of a high frequency of pulmonary microthrombi and other organs&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">77</span></a></p><p id="par0355" class="elsevierStylePara elsevierViewall">There is evidence of laboratory abnormalities of hypercoagulability and a high prevalence of thromboembolic events in adults with COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">78</span></a> Clinical studies demonstrated that 20&#8211;55&#37; of hospitalized patients show laboratory evidence of coagulopathy &#40;elevated D-dimer&#44; prolonged prothrombin time&#44; mild thrombocytopenia&#44; and&#47;or decreased fibrinogen&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">79</span></a> There is also evidence that a high D-dimer level is associated with a worse prognosis and an increased mortality rate&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">80</span></a> A retrospective study in adults with high D-dimer levels showed that those who received enoxaparin had a lower mortality rate than those without thromboprophylaxis&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">80</span></a> Such observations have led to the indication of anticoagulant therapy in adults&#46; In this population&#44; prophylactic anticoagulation with low molecular weight heparin has been a standard recommendation for all cases that require hospitalization for COVID-19 and have no contraindications&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">81</span></a></p><p id="par0360" class="elsevierStylePara elsevierViewall">In a series of MIS-C cases&#44; the use of anticoagulation was quite variable&#44; ranging from 12&#46;5&#37; to 90&#46;1&#37; of cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;36&#44;51&#44;63</span></a> The impact of anticoagulation on the clinical outcome cannot be assessed due to the numerous factors involved&#44; thus requiring the individualization of this therapy in the pediatric age group&#46;</p><p id="par0365" class="elsevierStylePara elsevierViewall">Microthrombosis&#44; and even thrombus in large vessels&#44; has been a worrying manifestation in COVID-19&#59; thus&#44; the hematologist should be involved in the initial care of a child with suspected MIS-C that has some evidence of hypercoagulability or critical status&#46; It is important that the pediatric emergency physician is aware of possible early interventions with the support of specialists to obtain the best outcomes&#46;</p><p id="par0370" class="elsevierStylePara elsevierViewall">Enoxaparin&#44; the most commonly used and studied anticoagulant in pediatric patients&#44; can be administered subcutaneously without requiring exclusive vascular access&#44; and has a half-life of 3&#8211;6<span class="elsevierStyleHsp" style=""></span>h via renal elimination&#46; Its effect is monitored by measuring anti-Xa&#44; and its action can be partially reversed with the administration of protamine&#46; Laboratory control prior to heparinization includes complete blood count to assess the presence of thrombocytopenia&#44; coagulogram&#44; and renal function assessment&#44; which are already part of the control of every critical patient&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">82</span></a><a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> shows the dose of enoxaparin used in children&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0375" class="elsevierStylePara elsevierViewall">The spectrum of involvement of COVID-19 in adults and children differs&#59; therefore&#44; the recommendations for adults do not apply directly to the pediatric population&#46; Anticoagulation should be performed in the context of clinical trials or in consultation with specialists&#46; Pediatric clinical trials using anticoagulants for thromboprophylaxis are ongoing&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">83</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Convalescent plasma</span><p id="par0380" class="elsevierStylePara elsevierViewall">In a Cochrane review evaluating the use of convalescent plasma in patients with COVID-19&#44; eight studies of 32 patients were identified&#46; The authors found a very low level of evidence considering the efficacy and safety of using this therapeutic modality&#46; Randomized controlled studies using convalescent plasma are in progress&#59; however&#44; pediatric patients have not been included&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">84</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Extracorporeal membrane oxygenation</span><p id="par0385" class="elsevierStylePara elsevierViewall">ECMO can be considered a therapeutic modality in referral services in patients with hypoxemia and refractory hypercapnia&#44; septic and&#47;or cardiogenic shock refractory to vasoactive drugs&#44; and failure of a single organ with minor comorbidity&#46; Contraindications for ECMO must follow established guidelines&#44; which broadly include severe and multiple comorbidities&#44; immunocompromised status&#44; chronic lung disease&#44; conditions that are contraindications for anticoagulation&#44; and severe neurological conditions&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">85</span></a></p><p id="par0390" class="elsevierStylePara elsevierViewall">ECMO was approved by the FDA as a therapy during the COVID-19 pandemic&#44; and the WHO suggests its use for COVID-19 patients with refractory hypoxemia despite the use of protective ventilation&#44; emphasizing that it is a very limited resource that must be rationed in a pandemic situation&#46;</p><p id="par0395" class="elsevierStylePara elsevierViewall">In a pediatric series&#44; ECMO was used in a minority of MIS-C cases&#44; ranging from 5&#37; to 12&#46;5&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">36&#44;41&#44;51</span></a> The assessment of the true impact of this therapy is not yet possible&#46;</p><p id="par0400" class="elsevierStylePara elsevierViewall">The role of ECMO and its indication during the pandemic must be considered&#44; taking into account the scarcity of resources and specialized professionals&#44; since it is a highly complex procedure and requires an expert team&#46;</p><p id="par0405" class="elsevierStylePara elsevierViewall">The great challenge for pediatricians is recognizing cases of children in the emergency department who present clinically with MIS-C associated with COVID-19 and defining the indication and the ideal time for the immunomodulatory therapeutic approach&#46; For the proper management of patients in critical condition due to a little-known disease&#44; specialist involvement is necessary in the emergency room&#46;</p></span><span id="sec0091" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0121">Algorithm&#58; Proposal approach to MIS-C related to COVID-19 at the Emergency Department</span><p id="par0411" class="elsevierStylePara elsevierViewall">The proposal approach is present in the algorithm in <a class="elsevierStyleCrossRef" href="#sect0111">Fig&#46; 3</a>&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Final considerations</span><p id="par0410" class="elsevierStylePara elsevierViewall">In a short period of time&#44; much has been learned about MIS-C temporally associated with COVID-19&#59; however&#44; numerous uncertainties persist&#46; Although it is a rare disease&#44; it comprises a variable spectrum of symptoms and severity and may have a turbulent evolution consisting of multiple organ failure and the need for intensive care&#46;</p><p id="par0415" class="elsevierStylePara elsevierViewall">The pediatric emergency department is the main gateway for children and adolescents with suspected MIS&#46; This review aimed to contribute to the dissemination of current knowledge and instruct pediatricians in early diagnosis and treatment&#46; Pediatric specialists should be involved in decision-making&#44; either in person or remotely&#44; and immunomodulatory therapy should not be delayed in severe cases&#46;</p><p id="par0420" class="elsevierStylePara elsevierViewall">Patients with clinical instability should be referred to the ICU&#44; but in the absence of available spaces&#44; supportive therapy&#44; immunomodulation&#44; and even anticoagulation&#44; when properly indicated&#44; should be initiated in the emergency department&#46; The emergency room pediatrician should not hesitate to seek help and guidance&#46;</p><p id="par0425" class="elsevierStylePara elsevierViewall">Many challenges must still be overcome in understanding this disease&#46; It is important to clarify whether MIS-C is a new condition or shares a common mechanism with other pathologies&#46; Evidence points to an immune-mediated disease with SARS-CoV-2 as a trigger&#46; Causality with SARS-CoV-2 cannot be proven&#44; but the temporality associated with COVID-19 is remarkable&#44; highlighting the importance of conducting serology and viral research&#46;</p><p id="par0430" class="elsevierStylePara elsevierViewall">COVID-19 in children appears to present differently from that in elderly adults or those with comorbidities&#44; but it bears some resemblance to the involvement of young adults&#44; since the cytokine storm syndrome seems more evident&#44; affecting the myocardium&#46; Aggression to the heart seems to be constant in MIS-C&#44; with myocarditis being observed in older children and adolescents and Kawasaki-like disease observed in preschoolers&#46; Similarities with Kawasaki-like disease may increase our understanding of Kawasaki disease&#44; whose etiology is currently unknown&#46;</p><p id="par0435" class="elsevierStylePara elsevierViewall">Finally&#44; it is worth mentioning that the emergency department pediatrician must also be aware of differential diagnoses&#44; especially sepsis and toxic shock syndrome&#44; that require aggressive supportive therapy and antibiotic therapy&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflicts of interest</span><p id="par0440" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Multisystem inflammatory syndrome in children &#40;MIS-C&#41; associated with coronavirus disease &#40;COVID-19&#41; is a rare and challenging diagnosis requiring early treatment&#46; The diagnostic criteria involve clinical&#44; laboratory&#44; and complementary tests&#46; This review aims to draw pediatrician attention to this diagnosis&#44; suggesting early treatment strategies&#44; and proposing a pediatric emergency care flowchart&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Sources</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The PubMed&#47;MEDLINE&#47;WHO COVID-19 databases were reviewed for original and review articles&#44; systematic reviews&#44; meta-analyses&#44; case series&#44; and recommendations from medical societies and health organizations published through July 3&#44; 2020&#46; The reference lists of the selected articles were manually searched to identify any additional articles&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Summary of the findings</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">COVID-19 infection is less severe in children than in adults&#44; but can present as MIS-C&#44; even in patients without comorbidities&#46; There is evidence of an exacerbated inflammatory response with potential systemic injury&#44; and it may present with aspects similar to those of Kawasaki disease&#44; toxic shock syndrome&#44; and macrophage activation syndrome&#46; MIS-C can develop weeks after COVID-19 infection&#44; suggesting an immunomediated cause&#46; The most frequent clinical manifestations include fever&#44; gastrointestinal symptoms&#44; rash&#44; mucous membrane changes&#44; and cardiac dysfunction&#46; Elevated inflammatory markers&#44; lymphopenia&#44; and coagulopathy are common laboratory findings&#46; Supportive treatment and early immunomodulation can control the intense inflammatory response and reduce complications and mortality&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">MIS-C associated with COVID-19 is serious&#44; rare&#44; and potentially fatal&#46; The emergency department pediatrician must recognize and treat it early using immunomodulatory strategies to reduce systemic injury&#46; Further studies are needed to identify the disease pathogenesis and establish the most appropriate treatment&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Sources"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Summary of the findings"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:3 [
            "apendice" => "<p id="par0186" class="elsevierStylePara elsevierViewall">The following is Supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "titulo" => "Supplementary data"
            "identificador" => "sec0082"
          ]
        ]
      ]
    ]
    "multimedia" => array:8 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1864
            "Ancho" => 2501
            "Tamanyo" => 203466
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Interrelationship between the four plasma mediator systems triggered by the activation of factor XII &#40;Hageman factor&#41;&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Kumar et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1806
            "Ancho" => 2500
            "Tamanyo" => 528376
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">COVID 19 disease and MIS-C related to COVID-19&#46; The figure illustrates 4 escalating progressive phases of the disease&#44; according to evolution&#44; severity&#44; clinical signs and symptoms&#44; infectious vs inflammatory host response&#44; diagnosis tests and lab and imaging findings&#46; RT-PCR&#44; reverse transcription-polymerase chain reaction&#59; PCT&#44; procalcitonin&#59; CRP&#44; C-reactive protein&#59; TG&#44; triglycerides&#59; CT&#44; computed tomography&#59; ECHO&#44; echocardiography&#59; EKG&#44; electrocardiogram&#59; EEG&#44; electroencephalography&#59; IL&#44; interleukin&#59; CK&#44; creatine kinase&#59; LDH&#44; lactate dehydrogenase&#59; IgG&#44; immunoglobulin G&#59; BNP&#44; B-type natriuretic peptide&#59; Na&#44; natrium&#59; NK&#44; natural killer&#59; WBC&#44; white blood count&#59; ESR&#44; erythrocyte sedimentation rate&#59; BUN&#44; blood urea nitrogen&#59; C&#44; creatinine&#59; SARS CoV-2&#44; severe acute respiratory syndrome coronavirus 2&#59; MIS-C&#44; multisystem inflammatory syndrome in children and adolescents&#59; US&#44; ultrasound&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">SIRS&#44; systemic inflammatory response syndrome&#44; HLH&#44; hematophagocytic lymphohistiocytosis&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Castillo and Carcillo&#44; with modifications&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Hematophagocytic lymphohistiocytosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sepsis&#47;SIRS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Molecular diagnosis&#58; present&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Molecular diagnosis&#58; absent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Five of the following eight criteria&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Splenomegaly&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Visceromegaly&#43;&#47;&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cytopenia of two of three lineages&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cytopenia of two of three lineages&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hgb &#60;9 g&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hgb &#60;9 g&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Platelets 100<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Platelets 100<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Neutrophils &#60;1<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Neutrophils &#60;1<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hypertriglyiceridemia &#40;triglycerides &#62;265 mg&#47;dL&#41; or hyperfibrinogenemia &#60;1&#46;5 g&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hypertriglyceridemia &#40;triglycerides &#62;265 mg&#47;dL&#41; or hyperfibrinogenemia &#60;1&#46;5 g&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hemophagocytosis in bone marrow&#44; spleen or lymph nodes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hemophagocytosis in bone marrow&#44; spleen or lymph nodes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ferritin &#8805;500<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ferritin &#8805;500<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Low or absent NK cell activity &#40;according to local laboratory reference&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Low or absent NK cell activity &#40;according to local laboratory reference&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soluble CD 25 &#40;soluble IL2 receptor&#41; &#62;2400 U&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soluble CD 25 &#40;soluble IL2 receptor&#41; &#62;2400 U&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2547175.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Diagnostic criteria of HLH and clinical and laboratory manifestations of sepsis&#47;SIRS&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">ECHO&#44; echocardiography&#59; NT-proBNP&#44; N-terminal pro-B-type natriuretic peptide&#59; PT&#44; prothrombin time&#59; APTT&#44; activated partial thromboplastin time&#59; ESR&#44; erythrocyte sedimentation rate&#59; CRP&#44; C-reactive protein&#59; RT-PCR&#44; reverse transcription &#8211; polymerase chain reaction&#59; CPK&#44; creatine phosphokinase&#59; LDH&#44; lactate dehydrogenase&#59; IL&#44; interleukin&#59; MIS-C&#44; multisystem inflammatory syndrome in children&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Whittaker et al&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> with modifications&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">World Health Organization<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Royal College of Paediatrics and Child Health &#40;UK&#41;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Centers for Disease Control and Prevention &#40;USA&#41;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Denomination&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pediatric multisystem inflammatory syndrome temporally associated with COVID-19&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multisystem inflammatory syndrome in children &#40;MIS-C&#41; associated with coronavirus disease 2019 &#40;COVID-19&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;19 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;21 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;3 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805;38&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#59; persistent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever &#62;38&#46;0 for &#8805;24 h or reports of subjective fever lasting &#8805;24 h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical findings&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">AND</span> two of the following five&#58;1&#46; Rash or bilateral nonpurulent conjunctivitis or mucocutaneous inflammation signs &#40;oral&#44; hands&#44; or feet&#41;&#46;2&#46; Hypotension or shock&#46;3&#46; Acute gastrointestinal problems &#40;diarrhea&#44; vomiting&#44; or abdominal pain&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evidence of single or multiorgan dysfunction &#40;shock&#44; cardiac&#44; respiratory&#44; gastrointestinal&#44; or neurological disorder&#44; kidney&#41;&#46;Most patients hypotension and oxygen supplementary needing&#46;Some patients&#58; abdominal pain&#44; confusion&#44; conjunctivitis&#44; cough&#44; diarrhea&#44; headache&#44; edema&#44; lymphadenomegaly&#44; changes in mucous membranes&#44; cervical rash&#44; respiratory symptoms&#44; odynophagia&#44; hand and foot edema&#44; syncope and vomiting&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evidence of inflammation&#44; and evidence of clinically severe illness requiring hospitalization&#44; with multisystem &#40;&#62;2&#41; organ involvement &#40;cardiac&#44; kidney&#44; respiratory&#44; hematologic&#44; gastrointestinal&#44; dermatologic&#44; or neurological&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Laboratory changes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46; Features of myocardial dysfunction&#44; pericarditis&#44; valvulitis&#44; or coronary abnormalities &#40;including ECHO findings or elevated troponin&#47;NT-proBNP&#41;&#46;5&#46; Evidence of coagulopathy &#40;by PT&#44; APTT&#44; elevated D-dimers&#41;&#46;<span class="elsevierStyleBold">AND</span> Elevated markers of inflammation such as ESR&#44; CRP&#44; or procalcitonin&#46;<span class="elsevierStyleBold">AND</span> No other obvious microbial cause of inflammation&#44; including bacterial sepsis&#44; staphylococcal or treptococcal shock syndromes&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inflammation signs&#46;All patients&#58; elevated CRP&#44; ferritin and D-Dimer&#44; abnormal fibrinogen&#44; hypoalbuminemia and neutrophilia&#46;Some patients&#58; anemia&#44; kidney failure&#44; coagulopathy&#44; neutrophilia&#44; proteinuria&#44; increased CPK&#44; LDH&#44; troponin&#44; transaminases&#44; triglycerides&#44; thrombocytopenia&#44; increased IL-6 &#40;if available&#41; and IL-10 &#40;if available&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Laboratory evidence including&#44; but not limited to&#44; &#8805;1 of the following&#58; an elevated CRP level&#44; ESR&#44; fibrinogen&#44; procalcitonin&#44; D-dimer&#44; ferritin&#44; lactic acid dehydrogenase&#44; or IL-6&#59; elevated neutrophils&#59; reduced lymphocytes&#59; and low albumin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evidence of SARS-CoV-2 infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">AND</span> Evidence of COVID-19 &#40;RT-PCR&#44; antigen test&#44; or serology positive&#41;&#44; or likely contact with patients with COVID-19&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SARS-CoV-2 PCR test results may be positive or negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">AND</span> Positive for current or recent SARS-CoV-2 infection by RT-PCR&#44; serology&#44; or antigen test&#59; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Exclusion criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Another obvious cause of infection or inflammation&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Exclusion of any other microbial cause&#44; including bacterial sepsis&#44; staphylococcal or streptococcal shock syndromes&#44; infections associated with myocarditis such as enterovirus &#40;waiting for results of these investigations should not delay seeking expert advice&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">AND</span> No alternative plausible diagnoses&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Considerations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Consider this syndrome in children with features of typical or atypical Kawasaki disease or toxic shock syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Include children fulfilling full or partial criteria for Kawasaki disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Some individuals may meet the full or partial criteria for Kawasaki disease&#44; but should be reported if they meet the case definition for MIS-C&#46;Consider MIS-C in any pediatric death with evidence of SARS-CoV-2 infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Case definitions for multisystem inflammatory syndrome during the COVID-19 pandemic&#46;</p>"
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        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">RT-PCR&#44; reverse transcription &#8211; polymerase chain reaction&#59; PCT&#44; procalcitonin&#59; CRP&#44; C-reactive protein&#59; TG&#44; triglycerides&#59; CT&#44; computed tomography&#59; ECHO&#44; echocardiography&#59; EKG&#44; electrocardiogram&#59; EEG&#44; electroencephalography&#59; IL&#44; interleukin&#59; CK&#44; creatine kinase&#59; LDH&#44; lactate dehydrogenase&#59; IgG&#44; immunoglobulin G&#59; BNP&#44; B-type natriuretic peptide&#59; Na&#44; natrium&#59; NK&#44; natural killer&#59; ESR&#44; erythrocyte sedimentation rate&#59; SARS-CoV-2&#44; severe acute respiratory syndrome coronavirus 2&#59; MIS-C&#44; multisystem inflammatory disorder in children and adolescents&#59; INR&#44; international normalized ratio&#59; LV&#44; left ventricular&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Author&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Symptoms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SARS-CoV-2 detection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Laboratory tests&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Imaging findings&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Riphagen et al&#46;United Kingdom<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#8211;14 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Unrelenting fever&#44; rash&#44; conjunctivitis&#44; peripheral edema&#44; extremity pain&#44; gastrointestinal symptoms&#44; refractory shock&#44; pleural and pericardial effusions and ascitic No significant respiratory involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">RT-PCR</span> not detected<span class="elsevierStyleBold">Serology</span> not specified&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8593; CRP&#8593; PCT&#8593; ferritin&#8593; triglycerides&#8593; D-dimerNegative blood culturesOne positive RT-PCR enterovirus&#47;adenovirus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">X-Ray&#47;CT</span>&#58;Lung consolidations&#44; pleural effusion&#44; ascites&#44; ileitis<span class="elsevierStyleBold">ECHO and EKG</span>&#58; non-specific EKG&#44; echobrightcoronary vessels giant coronary aneurysm&#44; arrhythmia&#44; myocardial dysfunction&#44; ventricular dilatation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Whittaker et al&#46;United Kingdom and USA<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#8211;14 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&#44; sore throat&#44; headache&#44; vomiting&#44; abdominal pain&#44; and diarrhea Rash&#44; conjunctival injection&#44; lymphadenopathy&#44; mucus membrane alterations and red cracked lips&#44; swollen hands and feet&#44; acute kidney injury and shock&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">RT-PCR</span> detected &#40;26&#37;&#41;<span class="elsevierStyleBold">Serology</span> IgG detected &#40;87&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8593; CRP and neutrophil counts&#8595; albumin and lymphocyte counts&#8593; troponin and BNP concentrations compared with those without shock&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">ECHO and EKG</span>&#58; non-specific EKG myocardial dysfunction&#44; arrhythmia&#44; coronary abnormalities such as aneurysms and giant aneurysms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Toubiana et al&#46;France &#40;Paris&#41;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#8211;16 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Recent history of headache&#44; cough&#44; coryza&#44; fever&#44; anosmia&#46; ageusia Polymorphous skin rash&#44; changes to the lips&#47;oral cavity&#44; conjunctival injection&#44; gastrointestinal symptoms &#40;abdominal pain&#44; vomiting&#44; diarrhea&#41;&#44; peritoneal effusion&#44; irritability&#44; headaches&#44; confusion&#47;meningeal irritation&#46; Myocarditis&#44; hypotensive shock&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">RT-PCR</span> detected &#40;38&#37;&#41;<span class="elsevierStyleBold">Serology</span> IgG detected &#40;90&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8593; CRP&#44; PCT&#44; lipase&#44; D-dimer&#44; troponin&#44; and BNP&#8595; albumin&#8595; lymphocytes and platelets count&#59; neutrophil count &#8593;&#8593; alanine transaminasesand &#947;-glutamyltransferase&#8593; IL-6&#8595; NaAcute kidney injuryAnemiaNo other pathogen was identified&#44; except one serology suggestive of recent Epstein-Barr virus infectionCerebrospinal fluid pleocytosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">X Ray&#47;CT&#58;</span>Ground glass opacities&#44; local patchy shadowing&#44; interstitial abnormalities<span class="elsevierStyleBold">ECHO and EKG&#58;</span>Increased QT interval&#44; arrhythmias&#44; signs of ischemia&#44; pericardial effusions&#44; myocardial dysfunctionCoronary artery abnormalities&#44; such as increased visibility and dilations&#46;No coronary aneurysms identified&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Belhadjer et al&#46;France and Switzerland<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2-16 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&#44; asthenia &#40;100&#37;&#41;Abdominal pain&#44; vomiting&#44; diarrhea &#40;80&#37;&#41;&#44; respiratory distress &#40;65&#37;&#41;&#44; skin rash&#44; cheilitis&#44; cervical adenopathy&#44; meningism&#44; chest pain&#44; heart failure&#44; cardiogenic shock&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">RT-PCR</span> detected &#40;40&#37;&#41;<span class="elsevierStyleBold">Serology</span> IgG detected &#40;86&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8593; CRP&#44; PCT&#44; D-dimer&#44; troponin&#44; and BNP&#8593; leukocytes and neutrophils&#8593; IL-6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">ECHO and EKG</span>&#58;Unspecific EKG&#44; signs of ischemia&#8595; LV ejection fraction&#44; hypokinesis&#44; pericardial effusion&#44; coronary arteries dilatationNo coronary aneurysm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Verdoni et al&#46;Italy &#40;Bergamo&#41;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#8211;16 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non-exudative conjunctivitis&#44; alterations of the lips or oral cavity&#44; polymorphic rash&#44; lymphadenopathy&#44; diarrhea&#44; coronary aneurysm&#44; pericardial effusion&#44; meningeal signs&#44; hypotension&#44; and clinical signs of hypoperfusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">RT-PCR</span> detected &#40;20&#37;&#41;<span class="elsevierStyleBold">Serology</span> IgG detected &#40;80&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8593; CRP&#44; ferritin&#44; triglycerides&#44; transaminases&#44; D-dimer&#44; ESR&#44; and fibrinogen&#8595; Na and albumin&#8595; lymphocytes and platelets count&#8593; leukocytes and neutrophils&#8593; IL-6&#44; NK&#8593; CK&#44; troponin&#44; and BNPNo other pathogen was identified&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">ECHO</span>&#58; coronary aneurysm&#44; &#8595; ejection fraction&#44; valve regurgitation&#44; pericardial effusion<span class="elsevierStyleBold">X-ray</span>&#58; pneumonia&#44; minimal mono or bilateral infiltrates<span class="elsevierStyleBold">CT&#58;</span> bibasilar pulmonary thickening<span class="elsevierStyleBold">EEG</span>&#58; slow wave pattern&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Feldstein et al&#46;USA<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">186&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;3 years &#40;average&#41;1&#8211;14 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&#44; rash&#44; conjunctivitis&#44; oral mucosal alterations&#44; peripheral extremity changes&#44; lymphadenopathy&#44; abdominal pain&#44; tachycardia&#44; vomiting&#44; diarrhea&#44; cough&#44; dyspnea&#44; arthralgia&#44; myalgia&#44; myocarditis&#44; pericarditis&#44; arrhythmias&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">RT-PCR</span> detected &#40;77&#37;&#41;<span class="elsevierStyleBold">Serology</span> Ig detected &#40;88&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8593; CRP&#44; ferritin&#44; D-dimer&#44; fibrinogen&#44; troponin&#44; and BNP&#44; ESR&#44; INR&#44; ALT&#8595; hemoglobin and platelets&#8595; albuminLymphocytopeniaNeutrophilia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">ECHO&#58;</span> Coronary-artery aneurysms&#44; pericarditis&#44; pericardial effusion&#44; arrhythmia&#44; &#8595; ejection fraction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dufort et al&#46;USA<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0-20 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&#44; chills&#44; tachycardia&#44; abdominal pain&#44; vomiting&#44; diarrhea&#44; inflammation or enlargement of the appendix&#47;gallbladder&#44; hepatomegaly and&#47;or splenomegaly&#44; conjunctivitis&#44; oral mucosal alterations&#44; rash&#44; headache&#44; lymphadenopathy&#44; cough&#44; sore throat&#44; wheezing&#44; myocarditis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">RT-PCR</span> detected &#40;51&#37;&#41;<span class="elsevierStyleBold">Serology</span> IgG detected &#40;99&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8593; CPR&#44; PCT&#44; ferritin&#44; D-dimer&#44; fibrinogen&#44; troponin&#44; and BNP&#8593; IL-6&#8595; albumin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">ECHO</span>&#58; ventricular dysfunction&#44; pericardial effusion&#44; and coronary-artery aneurysm<span class="elsevierStyleBold">X Ray&#47;CT</span>&#58; opacity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Capone et al&#46; USA &#40;New York&#41;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;6 years &#40;average&#41;5&#46;5&#8211;12&#46;6 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&#44; clinical signs of complete or incomplete Kawasaki disease&#44; abdominal pain&#44; vomiting&#44; diarrhea&#44; headache&#44; irritability&#44; lethargy&#44; cough&#44; congestion&#44; dyspnea&#44; sore throat&#44; shock with cardiac dysfunction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">RT-PCR</span> detected &#40;9&#37;&#41;<span class="elsevierStyleBold">Serology</span> IgG detected &#40;91&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8593; CPR&#44; PCT&#44; ferritin&#44; transaminases&#44; D-dimer&#44; and fibrinogen&#8595; albumin&#8595; lymphocytes and platelets count&#59; normal neutrophil count or &#8593;&#8595; Na&#8593; LDH&#44; INR&#44; troponin&#44; and BNPAcute kidney injuryAnemiaNo other pathogen was identifiedOne positive RT-PCR influenza&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">ECHO</span>&#58; coronary abnormality&#44; dysfunction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">ICU&#44; intensive care unit&#59; ECMO&#44; extracorporeal membrane oxygenation&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Author&#47;country&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type of study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age &#40;median&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical evolution&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Grimaud et al&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a>France&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Atypical Kawasaki and severe inflammatory multisystem disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;9&#8211;15 years&#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; ICU100&#37; myocarditis100&#37; cardiogenic shock95&#37; vasoactive support40&#37; mechanical ventilationThere were no deaths and all recovered left ventricular function&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; IGIV &#40;2g&#47;kg&#41;10&#37; corticosteroids5&#37; anakinra5&#37; tocilizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Toubiana et al&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a>France&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kawasaki-like multisystem inflammatory syndrome in children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;7&#8211;16&#46;6 years&#40;7&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">81&#37; ICU76&#37; myocarditis71&#37; vasoactive support52&#37; mechanical ventilationAll patients were discharged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; IGIV &#40;2g&#47;kg&#41;24&#37; 2nd IGIV dose48&#37; corticosteroids100&#37; Aspirin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kyotos et al&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">64</span></a>USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multisystem inflammatory syndrome in children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#8211;14 years&#40;7&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; ICU100&#37; cardiogenic shock83&#37; vasoactive support50&#37; mechanical ventilationAll were discharged with recovery of cardiac function&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; IGIV &#40;2g&#47;kg&#41;100&#37; corticosteroids2 patients 2nd IGIV dose1 patient anakinra and aspirin1 patient aspirin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Riphagen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>United Kingdom&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multisystem inflammatory syndrome in children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#8211;14 years&#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; ICU100&#37; vasoactive support87&#46;5&#37; mechanical ventilation87&#46;5&#37; myocardial dysfunction12&#46;5&#37; ECMOThere was one death&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; IGIV &#40;2g&#47;kg&#41;50&#37; corticosteroids25&#37; aspirin12&#46;5&#37; infliximab12&#46;5&#37; therapeutic heparin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Belhadjer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a>France&#44; Switzerland&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multisystem inflammatory syndrome in children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;16 years&#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; ICU100&#37; left ventricular dysfunction80&#37; inotropic support62&#37; mechanical ventilation28&#37; ECMOThere were no deaths&#46;Left ventricular function was restored in 25&#47;35 patients&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&#37; IGIV34&#37; corticosteroid65&#37; heparin3&#37; anakinra1 patient 2nd IGIV doseAuthors suggest that treatment with IVIG may be associated with ventricular recovery&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Verdoni et al&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a>Italy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kawasaki disease shock syndrome&#44; or severe Kawasaki-like disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;9&#8211;16 years&#40;7&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#37; myocardial dysfunction20&#37; inotropic support&#46;0&#37; mechanical ventilationAll patients were discharged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; IGIV &#40;2g&#47;kg&#41;80&#37; corticosteroid20&#37; aspirin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cheung et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multisystem inflammatory syndrome in children and adolescents&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;8&#8211;16 years&#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">88&#37; ICU59&#37; vasoactive support0&#37; mechanical ventilationThere were no deaths&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76&#37; IGIV &#40;2g-4g&#47;kg&#41;92&#37; corticosteroid24&#37; aspirin6&#37; tocilizumab59&#37; prophylactic enoxaparin6&#37; therapeutic enoxaparin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Whittaker et al&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a>England&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pediatric inflammatory multisystem syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;7&#8211;14 years&#40;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#37; cardiogenic shock50&#37; vasoactive support43&#37; mechanical ventilation5&#37; ECMOThere were two deaths&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&#37; IGIV64&#37; corticosteroid14&#37; infliximab5&#37; anakinraAssociation of two agents in 60&#37; of patients and three agents in 16&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Panupattanapong et al&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">61</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Review&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kawasaki-like syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Emerging phenotypes are a combination of typical or atypical Kawasaki disease&#44; Kawasaki shock syndrome&#44; toxic shock syndrome&#44; macrophage activation syndrome and hemophagocytic lymphohistiocytosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with criteria for Kawasaki disease&#44; atypical Kawasaki disease&#44; or coronary changes should receive IVIG &#40;2G&#47;kg&#41; and high doses of Aspirin&#46; If the hyperinflammatory component is prominent&#44; consider using corticosteroids&#44; tocilizumab&#44; or anakinra&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Miller et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a>USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multisystem inflammatory syndrome in children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 months&#8211;20 years&#40;7&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#37;&#58; vasoactive support50&#37;&#58; cardiac abnormality1 patient&#58; mechanical ventilationThere were no deaths&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">82&#37; IGIV &#40;2g&#47;kg&#41;95&#37; corticosteroids18&#37; anakinra90&#37; Anticoagulation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Feldstein et al&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multisystem inflammatory syndrome in children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">186&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;3&#8211;12&#46;5 years&#40;8&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#37; vasoactive support20&#37; mechanical ventilation8 &#40;4&#37;&#41; ECMOThere were 4 deaths &#40;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77&#37; IGIV &#40;2g&#47;kg&#41;49&#37; corticosteroids13&#37; anakinra8&#37; IIL-6 inhibitor47&#37; Anticoagulation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dufort et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multisystem inflammatory syndrome in children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Under 21 years31&#37; &#40;0-5 years&#41;42&#37; &#40;6-12 years&#41;25&#37; &#40;13-20 years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#37; vasoactive support10&#37; mechanical ventilation53&#37; myocarditis4 &#40;4&#37;&#41; ECMOThere were 2 deaths &#40;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#37; IGIV &#40;2g&#47;kg&#41;64&#37; corticosteroids48&#37; IVIG and corticosteroids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">European Center for Disease Prevention and Control<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a>Europe and North America&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Guideline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pediatric multisysteminflammatory syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">322&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Literature review with clinical description&#44; risk factors&#44; severity&#44; treatment and communication of the disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">If Kawasaki&#39;s disease is part of the differential diagnosis&#44; the use of IVIG has been the predominant approach&#46;Corticosteroids and anti-TNF monoclonal antibodies have also been used&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Capone et al&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a>USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pediatric multisystem inflammatory syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;2&#8211;17 years&#40;8&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79&#37; ICU76&#37; vasoactive support58&#37; myocardial dysfunction48&#37; coronary abnormality64&#37; complete Kawasaki diseaseThere were no deaths&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; IGIV33&#37; 2nd dose IVIG70&#37; corticosteroid88&#37; aspirin12&#37; anakinra9&#37; tocilizumab3&#37; infliximab42&#37; enoxaparin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Giglia et al&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">82</span></a> and Monagle et al&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">86</span></a></p><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">SC&#44; subcutaneously&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Under 2 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;75 mg&#47;kg&#47;dose SC 12&#47;12h or1&#46;5 mg&#47;kg&#47;dose SC every 24h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;7 mg&#47;kg SC every 12h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Over 2 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5 mg&#47;kg&#47;dose SC 12&#47;12h or1 mg&#47;kg&#47;dose SC every 24h&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;0 mg&#47;kg SC every 12h&nbsp;\t\t\t\t\t\t\n
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      "titulo" => "References"
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          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:86 [
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              "identificador" => "bib0005"
              "etiqueta" => "1"
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                0 => array:1 [
                  "referenciaCompleta" => "World Health Organization&#46; Responding to community spread of COVID-19&#58; interim guidance&#46; Available from&#58; <a target="_blank" href="https://www.who.int/publications/i/item/responding-to-community-spread-of-covid-19">https&#58;&#47;&#47;www&#46;who&#46;int&#47;publications&#47;i&#47;item&#47;responding-to-community-spread-of-covid-19</a> &#91;cited 7&#46;3&#46;20&#93;&#46;"
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            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk for transportation of coronavirus disease from Wuhan to other cities in China"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Z&#46; Du"
                            1 => "L&#46; Wang"
                            2 => "S&#46; Cauchemez"
                            3 => "X&#46; Xu"
                            4 => "X&#46; Wang"
                            5 => "B&#46;J&#46; Cowling"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3201/eid2605.200146"
                      "Revista" => array:6 [
                        "tituloSerie" => "Emerg Infect Dis"
                        "fecha" => "2020"
                        "volumen" => "26"
                        "paginaInicial" => "1049"
                        "paginaFinal" => "1052"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32053479"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "WHO declares COVID-19 a pandemic"
                      "autores" => array:1 [
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                          "etal" => false
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                            1 => "M&#46; Vanelli"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.23750/abm.v91i1.9397"
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Biomed"
                        "fecha" => "2020"
                        "volumen" => "91"
                        "paginaInicial" => "157"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32191675"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "COVID-19 and cardiovascular disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                            0 => "K&#46;J&#46; Clerkin"
                            1 => "J&#46;A&#46; Fried"
                            2 => "J&#46; Raikhelkar"
                            3 => "G&#46; Sayer"
                            4 => "J&#46;M&#46; Griffin"
                            5 => "A&#46; Masoumi"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Circulation"
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              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Angiotensin-converting enzyme 2 &#40;ACE2&#41; is a key modulator of the renin angiotensin system in health and disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "C&#46; Tikellis"
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                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
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            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Angiotensin-converting enzyme 2 &#40;ACE2&#41; as a SARS-CoV-2 receptor&#58; molecular mechanisms and potential therapeutic target"
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                        0 => array:2 [
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                          "autores" => array:5 [
                            0 => "H&#46; Zhang"
                            1 => "J&#46;M&#46; Penninger"
                            2 => "Y&#46; Li"
                            3 => "N&#46; Zhong"
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                      ]
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                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00134-020-05985-9"
                      "Revista" => array:6 [
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                        "volumen" => "46"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32125455"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The intriguing features of COVID-19 in children and its impact on the pandemic"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "M&#46;A&#46; Safadi"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Pediatr &#40;Rio J&#41;"
                        "fecha" => "2020"
                        "volumen" => "96"
                        "paginaInicial" => "265"
                        "paginaFinal" => "268"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "COVID-19 in 7780 pediatric patients&#58; a systematic review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Hoang"
                            1 => "K&#46; Chorath"
                            2 => "A&#46; Moreira"
                            3 => "M&#46; Evans"
                            4 => "F&#46; Burmeister-Morton"
                            5 => "F&#46; Burmeister"
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                        ]
                      ]
                    ]
                  ]
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Review article
Multisystem inflammatory syndrome associated with COVID-19 from the pediatric emergency physician's point of view
Hany Simon Juniora,b,
Corresponding author
hanyjr@uol.com.br

Corresponding author.
, Tania Miyuki Shimoda Sakanoa,b, Regina Maria Rodriguesa,b, Adriana Pasmanik Eisencrafta,b, Vitor Emanoel Lemos de Carvalhoa,b, Claudio Schvartsmana,b, Amelia Gorete Afonso da Costa Reisa,b
a Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Instituto da Criança, Departamento Emergência, São Paulo, SP, Brazil
b Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Instituto da Criança, São Paulo, SP, Brazil
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Interrelationship between the four plasma mediator systems triggered by the activation of factor XII &#40;Hageman factor&#41;&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Kumar et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">In November 2019&#44; some severe pneumonia cases were reported in Wuhan&#44; China&#46; In December 2019&#44; the rapid increase in the number of these cases with an epidemiological association with the local market caught the attention of Chinese health authorities&#46; The cause of these outbreaks was identified in January 2020 as a coronavirus&#59; the World Health Organization &#40;WHO&#41; later called the virus severe acute respiratory syndrome coronavirus 2 &#40;SARS-CoV-2&#41; and the disease caused by it coronavirus disease &#40;COVID-19&#41;&#46; The disease quickly spread to other countries&#44; which led the WHO to declare an international public health emergency on January 30&#44; 2020 and a pandemic on March 1&#44; 2020&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">SARS-CoV-2 exerts a pathogenic mechanism by binding the spike protein on its surface to the type 2 angiotensin-converting enzyme &#40;ACE2&#41; receptor&#44; whose physiological action is to act as a regulatory mechanism against the effects of angiotensin&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> ACE2 receptors are significantly expressed in the lung&#44; mainly in type II pneumocytes&#44; the predominant site of the pathogenicity of the virus in the human body&#44; as well as in other organs such as the heart&#44; vascular endothelium&#44; intestinal epithelium&#44; and kidneys&#44; thus providing a favorable mechanism for multiple organ dysfunction&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The literature is consistent in stating that COVID-19&#44; a disease caused by SARS-CoV-2&#44; affects children more rarely and mildly than it affects adults&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> Some of the hypotheses that explain this phenomenon include differences in ACE2 receptor expression&#44; differences in the immune system &#40;better innate immune response in children&#44; especially when compared with the elderly&#44; and a lesser pro-inflammatory response with less cytokine production&#41;&#44; a lower prevalence of comorbidities&#44; lower exposure to the pathogen in the initial phase of the pandemic&#44; respiratory infections by other coronaviruses that are already circulating in the community&#44; greater colonization by other viruses and bacteria conferring interactions with the microbiota and competition&#44; and a greater risk of children being infected by the second or third generation of SARS-CoV-2&#44; a phenomenon that is generally associated with reduced aggressiveness&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Although COVID-19 is less severe and less frequent in children&#44; as the pandemic progresses&#44; there are reports of a worrying clinical picture in the pediatric age group&#44; with symptoms similar to Kawasaki disease and toxic shock that require assertive conduct by pediatricians&#44; especially those working in emergency services&#46; Similar reports have been reported in several countries under the name &#8220;multisystem inflammatory syndrome in children&#8221; &#40;MIS-C&#41; temporarily associated with COVID-19&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#8211;13</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The pathophysiology of MIS-C is unclear&#44; but it appears to be a consequence of an exacerbated immune system response or maladaptive response of the host&#46; After the virus enters the human cells&#44; the first line of defense against infection should be a quick and well-coordinated immune response&#59; however&#44; when this mechanism is unregulated and excessive&#44; hyperinflammation can occur&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Cytokines that play an important role in inducing immunity and immunopathology during infections in excess can cause the clinical syndrome known as cytokine storm&#46; The inflammatory response caused by SARS-CoV-2 appears to be the major cause of mortality in infected patients&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> The infection of dendritic cells or macrophages by SARS-CoV-2 induces the production of low levels of antiviral cytokines and increases the production of inflammatory cytokines &#40;tumor necrosis factor &#91;TNF&#93;&#44; interleukin &#91;IL&#93;-1&#44; IL-6&#44; and interferon-&#947;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#8211;19</span></a> An apparent action of inflammatory cytokines&#44; especially IL-6&#44; is the expression of tissue factor&#44; which leads to the activation of coagulation and the complement cascade and the release of inflammatory kinins<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> In addition&#44; the excessive production of IL-6&#44; IL-10&#44; and TNF is negatively correlated with the total number of lymphocytes affecting both innate and acquired immunity&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The massive release of inflammatory mediators with exaggerated activation of the immune system is similar to the syndrome known as cytokine storm&#44; which occurs in a group of conditions that share the same pathogenic mechanism but have different triggering factors&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> The neutrophil&#44; the main protagonist of the cytokine storm&#44; has the capacity to secrete ferritin&#44; which explains the high levels found in several inflammatory syndromes&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Ferritin&#44; in turn&#44; has an immunosuppressive action and inhibits the differentiation of myeloid cells and T and B lymphocytes&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> worsening the host&#39;s responsiveness&#46; High levels of ferritin and hemophagocytosis are related to inflammation severity and are present in several diseases with different etiologies&#58; macrophage activation syndrome&#44; hemophagocytic lymphohistiocytosis &#40;HLH&#41;&#44; sepsis&#44; multisystem inflammatory syndrome &#40;MIS&#41;&#44; staphylococcal toxic shock&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> and severe cases of COVID-19&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> suggesting that these are different phenotypes of the same inflammatory process&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Thus&#44; MIS-C appears to be a clinical syndrome that shares aspects with other inflammatory conditions in which large amounts of cytokines cause the dysfunction of several organs&#44; including Kawasaki disease&#44; sepsis&#44; macrophage activation syndrome&#44; and secondary HLH &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Its action on the vascular bed is very important&#44; causing hypotension and the leakage of fluids and immune system cells in the lung&#44; heart&#44; and other organs&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Cardiac involvement&#44; whether myocardial dysfunction&#44; pericarditis&#44; valve dysfunction&#44; or coronary abnormalities&#44; is noteworthy&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">The criteria for the clinical diagnosis of MIS-C&#44; according to the Royal College of Paediatrics and Child Health &#40;RCPCH&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> are shared by other inflammatory diseases &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Notably&#44; fever&#44; adenomegaly&#44; rash&#44; involvement of the mucous membranes&#44; edema of the hands and feet&#44; and involvement of the coronary arteries are clinical criteria for the diagnosis of Kawasaki disease&#46; The presence of fever and coronary abnormalities are symptoms of Kawasaki-like disease&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> which explains the connection to MIS-C associated with COVID-19&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">The laboratory criteria of MIS-C &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41; also include symptoms that overlap with HLH&#44; such as elevated triglycerides and ferritin and the involvement of two hematological series&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> HLH&#44; primary or secondary to infection&#44; is a complex clinical syndrome characterized by an excessive but ineffective inflammatory response&#44; intense macrophage activation&#44; tissue invasion by T lymphocytes&#44; and the secretion of large amounts of cytokines&#44; possibly due to the stimulation of Toll-like receptors&#46; The ability of SARS-CoV-2 to bind to these receptors justifies the presence of common laboratory parameters for COVID-19 and HLH&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Studies are needed to better understand MIS-C&#46; The challenges are related to the pathophysiological mechanisms&#44; diagnostic criteria&#44; and treatment strategies&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> The disease is rare&#44; affecting 2 in 100&#44;000 children under 21 years of age&#44; and it has a temporal relationship with COVID-19&#44; appearing two to four weeks after SARS-CoV-2 infection&#46; The initial approach to managing pediatric patients with suspected MIS most often occurs in the emergency department&#44; which requires that professionals working in this area&#44; especially pediatricians&#44; be prepared&#46; This review aims to contribute to this preparation&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Clinical presentation</span><p id="par0060" class="elsevierStylePara elsevierViewall">There is limited knowledge regarding SARS-CoV-2 infection in children&#46; The clinical picture is oligosymptomatic when compared with most adult patients<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a>&#59; most symptoms are those of upper respiratory tract infection and mild pneumonia<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> with some reports of gastrointestinal symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> However&#44; some publications &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41; recently reported acute and severe clinical manifestations in children and adolescents&#44; with an evolution to cardiogenic shock and the need for intensive care &#40;<a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">At the end of April 2020&#44; the United Kingdom issued an alert regarding the growing number of pediatric patients who had a clinical picture compatible with toxic shock&#44; signs similar to Kawasaki disease&#44; changes in hemodynamic parameters&#44; and gastrointestinal manifestations&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Evolution with cardiogenic shock&#44; the need for ventilatory support and vasoactive drugs&#44; coronary dilation&#44; and elevated inflammatory test results without evidence of pulmonary involvement were observed in eight patients with the initial picture of high fever&#44; skin rash&#44; non-purulent conjunctivitis&#44; abdominal pain&#44; and diarrhea&#46; One patient died&#46; SARS-CoV-2 positivity was identified through the investigation of viral RNA in two patients and adenovirus in another&#59; in others&#44; there was a history of contact with first-degree relatives with COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">A study of 14 pediatric intensive care units in France and Switzerland reported 35 children who developed severe cardiac decompensation with signs of MIS-C associated with COVID-19&#46; The laboratory diagnosis was made by polymerase chain reaction &#40;PCR&#41; detection in a nasopharyngeal swab and&#47;or positive serology in 31 of the 35 patients&#46; In this case series&#44; the clinical manifestations at admission were fever&#44; asthenia&#44; and gastrointestinal symptoms such as abdominal pain&#44; diarrhea&#44; and vomiting in 80&#37; of patients&#46; Some signs suggestive of Kawasaki disease&#44; such as skin rash&#44; cervical adenopathy&#44; cheilitis&#44; and meningism&#44; were also observed&#44; without meeting all classic clinical criteria of the disease&#46; The main laboratory findings revealed changes in inflammatory tests &#40;PCR&#44; erythrocyte sedimentation rate&#44; brain natriuretic peptide &#91;BNP&#93;&#44; interleukin-6&#44; D-dimer&#44; troponin I&#41; and on echocardiography&#44; with a relevant reduction in ejection fraction and left ventricular hypokinesia in most patients&#46; All patients required intensive care unit &#40;ICU&#41; admission&#44; 80&#37; used inotropic drugs&#44; 28&#37; used extracorporeal membrane oxygenation &#40;ECMO&#41; and two-thirds required mechanical ventilation&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> The improvement in myocardial dysfunction observed in this series suggests that the mechanism of heart failure may be more closely associated with the inflammatory process&#44; leading to the distention of myocardial fibers and activation of BNP rather than to the direct lesions of the virus&#46; Another noteworthy observation is that the disease occurred in an older age group compared to that usually affected by Kawasaki disease&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The New York State database on MIS-C has similarities with the European series&#46; On July 3&#44; 2020&#44; 230 cases had been reported with a total of two deaths&#46; The most prevalent symptoms are prolonged fever &#40;for more than five days&#41;&#44; abdominal pain&#44; diarrhea&#44; vomiting&#44; dyspnea or tachypnea&#44; paleness or cyanosis of extremities&#44; decreased urine output&#44; and lethargy or mental confusion&#46; Positive antigenic or serological tests for SARS-CoV-2 were observed in 94&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Two studies from the US<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37&#44;38</span></a> presented the largest case series related to MIS-C&#46; Using the same New York database&#44; Dufort EM et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> published a study of 191 patients&#44; among whom 95 had confirmed MIS-C and four had suspected MIS-C&#46; Regarding the definition of confirmed cases&#44; clinical criteria&#44; laboratory criteria &#40;alteration of at least two exams&#41;&#44; and serological evidence or molecular testing &#40;RT-PCR&#41; for SARS-CoV-2 were used&#46; Suspected cases were classified according to the clinical condition and epidemiological criteria&#46; All patients had fever&#44; 97&#37; had tachycardia&#44; 80&#37; had gastrointestinal symptoms&#44; 60&#37; had rash&#44; 57&#37; had conjunctivitis&#44; and 27&#37; had mucosal changes&#46; In this study&#44; some symptoms little described by other authors stand out&#44; such as hepatomegaly&#44; splenomegaly&#44; ascites&#44; inflammation&#44; and enlargement of the cecal appendix and gallbladder&#46; In addition&#44; it is evident that skin manifestations are common in children under 5 years of age&#44; and cases of myocarditis or cardiogenic shock are predominant in adolescents&#46; The authors also highlighted the presence of neurological symptoms in 13&#37; of children and 38&#37; of adolescents&#46; Dufort EM<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> and other authors emphasized the presence of encephalopathy&#44; headache&#44; signs of cerebellar alteration&#44; muscle weakness&#44; and reduced reflexes&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">A study of 186 patients across the United States reinforced the clinical and laboratory worsening&#44; mainly among patients over 10 years of age&#44; with inflammatory markers and cardiac enzymes with more significant changes&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">A study in Bergamo&#44; Italy&#44; compared a group of children with Kawasaki-like disease diagnosed before the COVID-19 pandemic with a group diagnosed during the pandemic&#46; In the latter&#44; an increase in the number of cases was observed by up to 30 times&#44; with more pronounced cardiac alterations&#44; a higher frequency of macrophage activation syndrome&#44; and&#44; as in reports from Europe&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> a predominance of older children affected&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">A UK publication described 58 children from eight ICU facilities with the clinical and laboratory criteria for MIS-C associated with COVID-19 caused by SARS-CoV-2 in 2020&#46; The mean age was 9 years&#44; and fever occurred in 100&#37; of cases&#44; vomiting in 45&#37;&#44; abdominal pain in 53&#37;&#44; diarrhea in 52&#37;&#44; and conjunctivitis in 45&#37;&#46; Shock due to myocardial dysfunction was observed in 50&#37; of the patients&#59; of those&#44; 79&#37; required mechanical ventilation and the use of inotropic drugs&#46; There was evidence of SARS-CoV-2 infection &#40;by serology and&#47;or reverse transcription-PCR &#91;RT-PCR&#93;&#41; in 78&#37; of the total patient group&#46; The authors compared the findings of these patients with those hospitalized from 2002 to 2019&#44; diagnosed with Kawasaki&#44; shock&#44; and toxic shock syndrome&#44; and observed older age &#40;9 years versus 2&#46;7 years&#41; and inflammatory tests with elevated levels&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> This corroborates the observation that the inflammatory state compatible with MIS-C associated with COVID-19 has a peculiar presentation&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Studies from Germany&#44; Austria&#44; and Portugal have also reported severe cases with gastrointestinal symptoms and increased inflammatory cytokines with an evolution compatible with Kawasaki-like or toxic shock syndrome associated with the detection of SARS-CoV-2 by RT-PCR or serology&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">No MIS-C case reports from China&#44; Japan&#44; or South Korea were retrieved&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> The multiple cases reported in the literature have led the WHO&#44; the US Centers for Disease Control and Prevention&#44; and the RCPCH to publish similar definitions of possible cases eligible for MIS-C &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;29</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">It is important to note that the period of MIS-C development after SARS-CoV-2 infection remains a matter of debate&#46; The disease can develop between the first and the second week after infection with the virus<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>&#59; however&#44; in patients with negative RT-PCR and serology test results&#44; the evolution to MIS-C can be considered within six weeks after patient exposure to COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Laboratory and imaging tests</span><p id="par0115" class="elsevierStylePara elsevierViewall">Complementary tests&#44; an integral part of the diagnostic criteria&#44; are not always available&#44; which can lead to diagnostic difficulties and treatment delays&#46; It is important for the pediatrician to raise the clinical suspicion and&#44; in the face of scarce resources&#44; arrange for referral to a more equipped emergency service&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Real time RT-PCR<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">43&#44;44</span></a> is the most recommended method for identifying SARS-CoV-2&#44; and the ideal period for its collection is between the fifth and sixth symptomatic day &#40;range&#58; third to seventh day&#41;&#46; If the sample is collected before the third day of illness and the result is negative&#44; a new collection is recommended on the third day&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Seroconversion is believed to occur after the seventh day of illness in 50&#37; of patients and in 14 days in all patients&#46; It is more relevant for epidemiological studies and can assist in COVID-19 diagnosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">43&#44;45</span></a> The possibility of cross-reactions leading to false-positive results in negative serum has not been ruled out&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">In observational studies of patients who developed MIS-C&#44; the probability of identifying SARS-CoV-2 infection by serology was two to three times higher than that by RT-PCR&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a> These findings are expected&#44; since MIS-C is a late form of the disease that occurs when the presence of the virus is no longer expected and the antibody rates are on the rise&#46; This makes serology particularly useful in correlating SARS-CoV-2 and MIS-C&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Inflammatory markers of organic function</span><p id="par0135" class="elsevierStylePara elsevierViewall">Considering that MIS-C is a late manifestation of COVID-19&#44; laboratory findings observed in the infectious phase of the disease maintain some diagnostic relevance even in the late inflammatory phase and may change&#44; significantly or not&#44; as the condition worsens &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Despite the lack of an absolute consensus&#44; most authors accept that disease deterioration changes blood count and inflammatory test results&#44; impairs liver and renal function &#40;hyperbilirubinemia&#44; hypertriglyceridemia&#44; and hypoalbuminemia&#41;&#44; changes coagulation&#44; changes myocardial enzymes&#44; and elevates kinins&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">The aspects that alert to MIS-C point to the presence&#44; although not always&#44; of one or more changes in inflammatory test results&#44; such as&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0150" class="elsevierStylePara elsevierViewall">Elevation of C-reactive protein &#40;CRP&#41;&#44; erythrocyte sedimentation rate&#44; procalcitonin&#44; D-dimer&#44; ferritin&#44; lactic dehydrogenase&#44; fibrinogen&#44; IL-6&#44; or neutrophils&#59; and</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0155" class="elsevierStylePara elsevierViewall">Reduction of lymphocytes and&#47;or albumin&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#44;49&#44;50</span></a></p></li></ul></p><p id="par0160" class="elsevierStylePara elsevierViewall">Feldstein et al&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> in a study published at the end of June 2020&#44; noticed that among the multiple tests performed on patients affected by MIS-C&#44; at least four were altered&#44; primarily increased CRP&#44; lymphopenia&#44; neutrophilia&#44; increased ferritin&#44; hypoalbuminemia&#44; and myocardial dysfunction&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Verdoni et al&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> when observing children and young people diagnosed with Kawasaki-like disease who developed coronary artery aneurysm in the pre- and post-SARS-CoV-2 era&#44; noticed a tendency toward inflammation and more pronounced cardiac injury markers in which CRP&#44; troponin&#44; ferritin&#44; and BNP were proven useful as predictors of disease worsening&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> In the same line of investigation&#44; Riphagen et al&#46; highlighted that patients who had elevated cardiac enzymes also had non-specific changes on electrocardiography &#40;ECG&#41; and echocardiography&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a> Whittaker et al&#46; warned of the recommendation to investigate these patients using echocardiography&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Imaging tests&#44; including ultrasound&#44; chest X-ray&#44; and chest tomography</span><p id="par0170" class="elsevierStylePara elsevierViewall">Pulmonary involvement in MIS-C is generally mild or non-existent&#46; Imaging tests are indicated for patients who have respiratory symptoms &#40;tachypnea&#44; dyspnea&#44; and&#47;or hypoxemia&#41;&#46; In this situation&#44; if available&#44; bedside ultrasound &#40;point of care ultrasound&#41; is preferable over others since it provides information comparable to chest tomography with the advantages of avoiding ionizing exposure and displacement of the patient&#44; allowing simultaneous assessment of the clinical and imaging information&#44; and reducing the risks of contamination of employees&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">On a progressive scale of worsening&#44; the most frequent ultrasound findings are irregular pleura&#44; B lines&#44; small pleural consolidations&#44; involvement of the upper and anterior areas&#44; consolidation&#44; air bronchography&#44; and pleural effusion&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Echocardiography and ECG</span><p id="par0180" class="elsevierStylePara elsevierViewall">Echocardiography and ECG are of fundamental relevance in MIS-C&#44; since myocardial and coronary involvement are critical points of unfavorable outcomes&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">The most significant findings of a review<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> of cardiac changes in COVID-19 were&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0190" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">ECG</span>&#58; Various aspects that mimic acute coronary syndrome&#44; non-specific changes in the ST segment&#44; an altered or inverted T wave&#44; or elevation or depression of PR or ST as a result of myocardial inflammation &#40;indicative of severity and worse prognosis&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0195" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Echocardiography</span>&#58; Dysfunction&#44; hypocontractility&#44; or even segmental absence of contractility in the myocardial chambers&#46; In this case&#44; alterations indicated severity and worse prognosis&#46;</p></li></ul></p><p id="par0200" class="elsevierStylePara elsevierViewall">In a prospective observational study of 21 children and young people with MIS-C&#44; pericardial effusion &#40;48&#37;&#41;&#44; pleural effusion &#40;14&#37;&#41;&#44; myocarditis &#40;76&#37;&#41; with a moderate to severe drop in left ventricular ejection fraction &#40;from 57&#37; to 10&#37;&#41;&#44; and coronary abnormalities &#40;38&#37;&#41;&#44; such as more pronounced brilliance or dilation without the identification of an aneurysm&#44; were observed&#46; Analyzing the ECG tracings&#44; the authors identified prolonged QT interval&#44; occasional ventricular arrhythmias&#44; and diffuse ST elevation&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Myocardial impairment has been found in autopsies of adults&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> In the English literature&#44; no articles correlating anatomopathological findings and disease caused by SARS-CoV-2 in childhood were retrieved&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> describes the laboratory and imaging findings according to COVID-19 progression &#40;mild&#44; moderate&#44; or severe and MIS-C&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Treatment</span><p id="par0215" class="elsevierStylePara elsevierViewall">MIS-C temporarily associated with COVID-19 is a rare but serious and potentially fatal presentation&#59; thus&#44; as in any condition where life is at risk&#44; there must be an emphasis on supportive treatment that includes oxygen supplementation&#59; ventilatory&#44; cardiovascular&#44; and renal support&#59; and pharmacotherapy in cases in which it is indicated&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> Supportive treatment does not differ from other situations and will not be outlined here&#44; as there are established pediatric guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Antibiotic administration cannot be delayed due to the possibility of toxic shock syndrome&#46; It is also important to highlight the team&#39;s mandatory use of personal protective equipment from the start of treatment&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Information regarding the indication and appropriate timing of potential treatments is limited&#44; and several centers consider the use of intravenous immunoglobulin &#40;IVIG&#41;&#44; corticosteroids&#44; immunomodulators&#44; anticoagulants&#44; and antiplatelet agents&#46; The selection of two or more immunomodulators to control the inflammatory condition has been described by several authors&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37&#44;38&#44;41&#44;60&#44;63</span></a> Patients with Kawasaki-like conditions who are classified as high risk for immunoglobulin resistance have been receiving a combination of IVIG with corticosteroids&#44; as this treatment appears to reduce the prevalence of coronary abnormalities and duration of fever&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;36</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">In addition to IVIG&#44; other potential strategies have been suggested to treat the cytokine storm&#46; The transfer of knowledge from the cytokine storm in the context of autoimmune and infectious diseases to a new viral disease is complex and challenging&#46; Evidence of hyperinflammation reinforces the therapeutic possibility of using immunomodulatory agents in COVID-19<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;56</span></a>&#59; in this scenario&#44; therapy with IVIG&#44; corticosteroids&#44; selective cytokine blockers &#40;anakinra&#44; tocilizumab&#41;&#44; anticoagulants&#44; remdesivir&#44; and convalescent plasma can reduce the inflammatory response and mortality&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">The use of medications is justified by the severity of the situation and the effectiveness in similar clinical conditions&#44; although the effectiveness in MIS-C has yet to be proven&#46; Evidence regarding each of these therapeutic modalities is provided in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Intravenous human immunoglobulin</span><p id="par0240" class="elsevierStylePara elsevierViewall">In addition to life support treatment&#44; IVIG is the predominant therapeutic option for MIS-C in different centers when Kawasaki disease is part of the differential diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> The RCPCH proposes that mild or moderate cases of MIS-C associated with COVID-19 be treated with supportive therapy&#44; that severe cases be admitted to the ICU&#44; and that the prescription of immunomodulators should be discussed with physicians who have experience using this type of medication&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Thus&#44; specialists such as infectologists&#44; rheumatologists&#44; immunologists&#44; or hematologists must be involved in the emergency treatment of MIS-C&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">The US National Institutes of Health reinforces a similar concept&#44; recognizing that there is limited information regarding the treatment of MIS-C associated with COVID-19&#44; and stating that supportive therapy is essential&#59; however&#44; many centers consider using IVIG&#44; corticosteroids&#44; and other immunomodulators&#44; although definitive data are not available&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">Most patients included in the MIS-C case series with a differential diagnosis of atypical Kawasaki or Kawasaki-like disease received IVIG &#40;2<span class="elsevierStyleHsp" style=""></span>g&#47;kg&#41;&#44; with frequent admission to the ICU and evolution with shock and myocardial dysfunction requiring vasoactive support&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">40&#44;47&#44;58&#8211;60</span></a> Case reports of COVID-19 and Kawasaki-like disease also suggested IVIG as therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">61</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">Siddiqi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a> proposed the use of immunomodulatory agents as therapeutic options in adults in the COVID-19 stage characterized by a state of hyperinflammation before multisystem organic damage occurs&#46; At this stage&#44; corticosteroids may be justified with or without the use of cytokine inhibitors or IVIG&#46; In general&#44; the prognosis and recovery of this critical stage of the disease are poor&#59; thus&#44; its rapid recognition and treatment are essential for a better evolution&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Belhadjer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> described a case series of 35 children admitted to the ICU diagnosed with MIS-C&#44; all of whom had myocardial dysfunction and 80&#37; of whom required hemodynamic support with inotropic agents&#46; Twenty-five patients received IVIG therapy and recovered myocardial function&#44; thus showing an association between IVIG use and good prognosis&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Miller et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a> reported on 44 patients with MIS-C and gastrointestinal symptoms&#59; among them&#44; none needed hemodynamic support and 81&#37; received IVIG&#46; The severity of the clinical presentation is common in the reports of MIS-C case series and deserves attention due to the high rate of patients requiring ICU admission and the high proportion of children with myocardial dysfunction&#44; cardiogenic shock&#44; and the need for vasoactive support&#46; Most of these patients received IVIG treatment and recovered myocardial function&#59; the evolution to death was an exception&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;41&#44;51&#44;60&#44;64</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">Dufort et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> reported on 99 children in New York State under 20 years of age who were diagnosed with MIS-C&#59; of them&#44; 70&#37; received IVIG&#46; It is noteworthy that the two children among them who died did not receive immunomodulatory treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> Another study of 26 states in the United States described 186 children and adolescents with fever for at least 24<span class="elsevierStyleHsp" style=""></span>hours&#44; multisystem involvement&#44; laboratory evidence of inflammation&#44; and SARS-CoV-2 infection&#46; IVIG treatment was used in 77&#37; of these patients&#59; 21&#37; received a second dose&#46; The authors propose that the choice of treatment should be based on the mechanisms of aggression&#44; <span class="elsevierStyleItalic">i&#46;e&#46;</span>&#44; active viral replication in the affected tissues&#44; the host&#39;s exuberant inflammatory response&#44; or both&#46; Antiviral agents are beneficial in the first situation&#44; whereas immunomodulatory agents are preferred in cases of immune dysregulation&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">The mechanism of action of IVIG is unknown in Kawasaki disease or in MIS-C associated with COVID-19&#46; It is likely associated with the global anti-inflammatory effect&#44; with modulation in the production of cytokines&#44; neutralization of toxins and other pathogens&#44; and increased regulatory activity of T cells&#44; among others&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;65</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Corticosteroids</span><p id="par0280" class="elsevierStylePara elsevierViewall">The use of corticosteroids in patients with SARS and Middle East respiratory syndrome &#40;recent coronavirus epidemics&#41; has not shown any influence on mortality in addition to increasing viral load and delaying viral clearing&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">66&#44;67</span></a> Furthermore&#44; the current WHO guideline does not recommend the universal use of corticosteroids in the treatment of severe COVID-19&#44; unless there was some other clinical condition in which the medication had a proven therapeutic effect&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> Immunosuppression can be beneficial in cases of hyperinflammatory states&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Although a randomized study using dexamethasone in adults reported an association between its use and a significant reduction in mortality&#44; these results cannot yet be applied to the pediatric age group&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">A meta-analysis of 2&#44;746 patients with Kawasaki disease demonstrated that the association of corticosteroids and immunoglobulin is related to a reduced risk of coronary aneurysm compared to isolated IVIG therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">68</span></a> The European consensus of Kawasaki disease recommends the use of corticosteroids in some conditions&#44; such as resistance to IVIG&#44; presentation as HLH&#44; presence of shock&#44; evidence of coronary and or peripheral aneurysms&#44; age less than 1 year&#44; and Kobayashi score &#8805;4&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">69</span></a> The suggested corticosteroid regimen is methylprednisolone 1&#46;6&#8211;2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day for 5&#8211;7 days or methylprednisolone 30<span class="elsevierStyleHsp" style=""></span>mg&#47;day for 3 days&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall">Corticosteroids &#40;methylprednisolone and hydrocortisone&#41; correspond to a treatment modality most used in MIS-C according to publications of pediatric case series as shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;34&#44;35&#44;40&#44;41&#44;47&#44;57&#44;58&#44;61</span></a> In most studies&#44; the dose of methylprednisolone was 2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg and the duration of therapy was not well defined&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">There is much doubt regarding the efficacy and safety of using corticosteroids in COVID-19&#44; and clinical studies are needed in all age groups&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">IL-6 inhibitors</span><p id="par0300" class="elsevierStylePara elsevierViewall">Tocilizumab is a recombinant monoclonal antibody that binds directly to the IL-6 receptor&#44; which&#44; in addition to crossing the blood&#8211;brain barrier and releasing prostaglandin E2&#44; triggers the increase in temperature&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> The inhibition of IL-6 receptors promotes a reduction in cytokine production&#44; thus configuring some indication of possible treatment for hyperinflammation&#44; although there are no studies in pediatric populations&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">Otocilizumab is indicated in adult patients with autoimmune diseases and is approved by the US Food and Drug Administration &#40;FDA&#41; for use in cytokine release syndrome in critical cases in adults and children&#46; Due to the similarities between the cytokine release syndrome and the cytokine storm in COVID-19&#44; studies are underway to evaluate the safety and efficacy of this therapeutic modality&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a></p><p id="par0310" class="elsevierStylePara elsevierViewall">Siltuximab&#44; another monoclonal antibody&#44; binds directly to IL-6 and can be considered a second-line treatment for COVID-19 cases resistant to tocilizumab&#44; although there is no evidence of its effectiveness to date&#46;</p><p id="par0315" class="elsevierStylePara elsevierViewall">Data are lacking in the pediatric age group to recommend or contraindicate the use of IL-6 inhibitors&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">IL-1 inhibitors</span><p id="par0320" class="elsevierStylePara elsevierViewall">The use of anakinra&#44; a recombinant IL-1 receptor antagonist&#44; has been suggested for modulating the effects of cytokines&#46; A randomized study in adult sepsis patients reported increased survival in patients with hyperinflammation who received anakinra without increasing adverse effects&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">70</span></a> Although there is no evidence of a correlation between serum IL-1 levels and COVID-19 severity&#44; ongoing multicenter studies have evaluated the role of anakinra associated with emapalumab in reducing hyperinflammation in patients with severe SARS-CoV-2 infection&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">Anakinra was used as additional therapy in MIS-C in 18&#46;2&#37; of cases in the American series<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a> and in 5&#37; of cases in the United Kingdom&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> and can be considered in the treatment of MIS-C that is refractory to IVIG and corticosteroids&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">71</span></a> The research field remains open&#44; as its role in this situation cannot be properly assessed&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">TNF inhibitors &#40;infliximab&#41;</span><p id="par0330" class="elsevierStylePara elsevierViewall">TNF is one among the factors that trigger the cytokine storm&#59; therefore&#44; its role in the treatment of SARS-CoV-2 infection deserves investigation&#46; A meta-analysis using anti-TNF showed improved survival in patients with sepsis&#44; a situation in which the role of cytokines is also relevant&#44;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">72</span></a> thus opening a therapeutic possibility in severe cases of COVID-19&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Medications with antiviral activity</span><p id="par0335" class="elsevierStylePara elsevierViewall">Remdesivir shows <span class="elsevierStyleItalic">in vitro</span> and <span class="elsevierStyleItalic">in vivo</span> activity against SARS-CoV-2 and other beta-coronaviruses&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">73</span></a> A multicenter randomized placebo-controlled study with adult patients hospitalized with COVID-19 pulmonary infection observed that the use of remdesivir decreased the length of hospital stay&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">74</span></a> The FDA has issued emergency use authorization for remdesivir for the treatment of severe COVID-19 in adults and children&#46; In Brazil&#44; remdesivir was not available at the time of this publication&#46;</p><p id="par0340" class="elsevierStylePara elsevierViewall">Other antivirals have been tested in adults with severe COVID-19&#46; The combination of lopinavir and ritonavir was used in a cohort of adult patients hospitalized with severe SARS-CoV-2 pneumonia with no evidence of superior results to those of standard treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">75</span></a> No studies with these medications in COVID-19 in children were retrieved&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Acetylsalicylic acid</span><p id="par0345" class="elsevierStylePara elsevierViewall">There are reports of use of acetylsalicylic acid &#40;ASA&#41; in cases of MIS-C in situations that meet Kawasaki-like criteria&#46; Since exacerbated inflammation is associated with organ damage and coronary aneurysm&#44; the anti-inflammatory action of ASA at a dose of 30&#8211;50<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day can be useful&#44; although there is no reliable evidence that a reduction in the rate of coronary abnormalities occurs in Kawasaki disease&#46; The antiplatelet action of ASA at a dose of 3&#8211;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day is indicated 48<span class="elsevierStyleHsp" style=""></span>h after fever defervescence and should be maintained for 6-8 weeks in cases where there are no coronary changes&#46; Some authors have suggested the use of continuous ASA in patients with coronary abnormalities to prevent thrombosis&#46; It is important to highlight that bleeding is a contraindication to ASA use and that care should be taken in the presence of thrombocytopenia and renal dysfunction&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;69</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Anticoagulation</span><p id="par0350" class="elsevierStylePara elsevierViewall">Anticoagulant therapy in pediatrics was mainly derived from studies in adults&#46; Cytokine storm causes activation of the coagulation cascade&#44; resulting in thrombosis&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;26</span></a> in addition to evidence of severe vascular injury in severe COVID-19&#46;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">76&#44;77</span></a> Autopsy findings confirm the state of hypercoagulability and extensive endothelial injury through the observation of a high frequency of pulmonary microthrombi and other organs&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">77</span></a></p><p id="par0355" class="elsevierStylePara elsevierViewall">There is evidence of laboratory abnormalities of hypercoagulability and a high prevalence of thromboembolic events in adults with COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">78</span></a> Clinical studies demonstrated that 20&#8211;55&#37; of hospitalized patients show laboratory evidence of coagulopathy &#40;elevated D-dimer&#44; prolonged prothrombin time&#44; mild thrombocytopenia&#44; and&#47;or decreased fibrinogen&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">79</span></a> There is also evidence that a high D-dimer level is associated with a worse prognosis and an increased mortality rate&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">80</span></a> A retrospective study in adults with high D-dimer levels showed that those who received enoxaparin had a lower mortality rate than those without thromboprophylaxis&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">80</span></a> Such observations have led to the indication of anticoagulant therapy in adults&#46; In this population&#44; prophylactic anticoagulation with low molecular weight heparin has been a standard recommendation for all cases that require hospitalization for COVID-19 and have no contraindications&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">81</span></a></p><p id="par0360" class="elsevierStylePara elsevierViewall">In a series of MIS-C cases&#44; the use of anticoagulation was quite variable&#44; ranging from 12&#46;5&#37; to 90&#46;1&#37; of cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;36&#44;51&#44;63</span></a> The impact of anticoagulation on the clinical outcome cannot be assessed due to the numerous factors involved&#44; thus requiring the individualization of this therapy in the pediatric age group&#46;</p><p id="par0365" class="elsevierStylePara elsevierViewall">Microthrombosis&#44; and even thrombus in large vessels&#44; has been a worrying manifestation in COVID-19&#59; thus&#44; the hematologist should be involved in the initial care of a child with suspected MIS-C that has some evidence of hypercoagulability or critical status&#46; It is important that the pediatric emergency physician is aware of possible early interventions with the support of specialists to obtain the best outcomes&#46;</p><p id="par0370" class="elsevierStylePara elsevierViewall">Enoxaparin&#44; the most commonly used and studied anticoagulant in pediatric patients&#44; can be administered subcutaneously without requiring exclusive vascular access&#44; and has a half-life of 3&#8211;6<span class="elsevierStyleHsp" style=""></span>h via renal elimination&#46; Its effect is monitored by measuring anti-Xa&#44; and its action can be partially reversed with the administration of protamine&#46; Laboratory control prior to heparinization includes complete blood count to assess the presence of thrombocytopenia&#44; coagulogram&#44; and renal function assessment&#44; which are already part of the control of every critical patient&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">82</span></a><a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> shows the dose of enoxaparin used in children&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0375" class="elsevierStylePara elsevierViewall">The spectrum of involvement of COVID-19 in adults and children differs&#59; therefore&#44; the recommendations for adults do not apply directly to the pediatric population&#46; Anticoagulation should be performed in the context of clinical trials or in consultation with specialists&#46; Pediatric clinical trials using anticoagulants for thromboprophylaxis are ongoing&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">83</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Convalescent plasma</span><p id="par0380" class="elsevierStylePara elsevierViewall">In a Cochrane review evaluating the use of convalescent plasma in patients with COVID-19&#44; eight studies of 32 patients were identified&#46; The authors found a very low level of evidence considering the efficacy and safety of using this therapeutic modality&#46; Randomized controlled studies using convalescent plasma are in progress&#59; however&#44; pediatric patients have not been included&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">84</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Extracorporeal membrane oxygenation</span><p id="par0385" class="elsevierStylePara elsevierViewall">ECMO can be considered a therapeutic modality in referral services in patients with hypoxemia and refractory hypercapnia&#44; septic and&#47;or cardiogenic shock refractory to vasoactive drugs&#44; and failure of a single organ with minor comorbidity&#46; Contraindications for ECMO must follow established guidelines&#44; which broadly include severe and multiple comorbidities&#44; immunocompromised status&#44; chronic lung disease&#44; conditions that are contraindications for anticoagulation&#44; and severe neurological conditions&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">85</span></a></p><p id="par0390" class="elsevierStylePara elsevierViewall">ECMO was approved by the FDA as a therapy during the COVID-19 pandemic&#44; and the WHO suggests its use for COVID-19 patients with refractory hypoxemia despite the use of protective ventilation&#44; emphasizing that it is a very limited resource that must be rationed in a pandemic situation&#46;</p><p id="par0395" class="elsevierStylePara elsevierViewall">In a pediatric series&#44; ECMO was used in a minority of MIS-C cases&#44; ranging from 5&#37; to 12&#46;5&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">36&#44;41&#44;51</span></a> The assessment of the true impact of this therapy is not yet possible&#46;</p><p id="par0400" class="elsevierStylePara elsevierViewall">The role of ECMO and its indication during the pandemic must be considered&#44; taking into account the scarcity of resources and specialized professionals&#44; since it is a highly complex procedure and requires an expert team&#46;</p><p id="par0405" class="elsevierStylePara elsevierViewall">The great challenge for pediatricians is recognizing cases of children in the emergency department who present clinically with MIS-C associated with COVID-19 and defining the indication and the ideal time for the immunomodulatory therapeutic approach&#46; For the proper management of patients in critical condition due to a little-known disease&#44; specialist involvement is necessary in the emergency room&#46;</p></span><span id="sec0091" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0121">Algorithm&#58; Proposal approach to MIS-C related to COVID-19 at the Emergency Department</span><p id="par0411" class="elsevierStylePara elsevierViewall">The proposal approach is present in the algorithm in <a class="elsevierStyleCrossRef" href="#sect0111">Fig&#46; 3</a>&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Final considerations</span><p id="par0410" class="elsevierStylePara elsevierViewall">In a short period of time&#44; much has been learned about MIS-C temporally associated with COVID-19&#59; however&#44; numerous uncertainties persist&#46; Although it is a rare disease&#44; it comprises a variable spectrum of symptoms and severity and may have a turbulent evolution consisting of multiple organ failure and the need for intensive care&#46;</p><p id="par0415" class="elsevierStylePara elsevierViewall">The pediatric emergency department is the main gateway for children and adolescents with suspected MIS&#46; This review aimed to contribute to the dissemination of current knowledge and instruct pediatricians in early diagnosis and treatment&#46; Pediatric specialists should be involved in decision-making&#44; either in person or remotely&#44; and immunomodulatory therapy should not be delayed in severe cases&#46;</p><p id="par0420" class="elsevierStylePara elsevierViewall">Patients with clinical instability should be referred to the ICU&#44; but in the absence of available spaces&#44; supportive therapy&#44; immunomodulation&#44; and even anticoagulation&#44; when properly indicated&#44; should be initiated in the emergency department&#46; The emergency room pediatrician should not hesitate to seek help and guidance&#46;</p><p id="par0425" class="elsevierStylePara elsevierViewall">Many challenges must still be overcome in understanding this disease&#46; It is important to clarify whether MIS-C is a new condition or shares a common mechanism with other pathologies&#46; Evidence points to an immune-mediated disease with SARS-CoV-2 as a trigger&#46; Causality with SARS-CoV-2 cannot be proven&#44; but the temporality associated with COVID-19 is remarkable&#44; highlighting the importance of conducting serology and viral research&#46;</p><p id="par0430" class="elsevierStylePara elsevierViewall">COVID-19 in children appears to present differently from that in elderly adults or those with comorbidities&#44; but it bears some resemblance to the involvement of young adults&#44; since the cytokine storm syndrome seems more evident&#44; affecting the myocardium&#46; Aggression to the heart seems to be constant in MIS-C&#44; with myocarditis being observed in older children and adolescents and Kawasaki-like disease observed in preschoolers&#46; Similarities with Kawasaki-like disease may increase our understanding of Kawasaki disease&#44; whose etiology is currently unknown&#46;</p><p id="par0435" class="elsevierStylePara elsevierViewall">Finally&#44; it is worth mentioning that the emergency department pediatrician must also be aware of differential diagnoses&#44; especially sepsis and toxic shock syndrome&#44; that require aggressive supportive therapy and antibiotic therapy&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflicts of interest</span><p id="par0440" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
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          "titulo" => "Introduction"
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          "identificador" => "sec0010"
          "titulo" => "Clinical presentation"
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        4 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Laboratory and imaging tests"
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        5 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Inflammatory markers of organic function"
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        6 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Imaging tests&#44; including ultrasound&#44; chest X-ray&#44; and chest tomography"
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        7 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Echocardiography and ECG"
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          "identificador" => "sec0035"
          "titulo" => "Treatment"
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          "identificador" => "sec0040"
          "titulo" => "Intravenous human immunoglobulin"
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          "identificador" => "sec0045"
          "titulo" => "Corticosteroids"
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          "identificador" => "sec0050"
          "titulo" => "IL-6 inhibitors"
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          "identificador" => "sec0055"
          "titulo" => "IL-1 inhibitors"
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          "identificador" => "sec0060"
          "titulo" => "TNF inhibitors &#40;infliximab&#41;"
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          "identificador" => "sec0065"
          "titulo" => "Medications with antiviral activity"
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          "titulo" => "Acetylsalicylic acid"
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          "titulo" => "Convalescent plasma"
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          "titulo" => "Extracorporeal membrane oxygenation"
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          "identificador" => "sec0091"
          "titulo" => "Algorithm&#58; Proposal approach to MIS-C related to COVID-19 at the Emergency Department"
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          "identificador" => "sec0090"
          "titulo" => "Final considerations"
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          "titulo" => "References"
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    "fechaRecibido" => "2020-07-21"
    "fechaAceptado" => "2020-08-21"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1348111"
          "palabras" => array:6 [
            0 => "Coronavirus disease &#40;COVID-19&#41;"
            1 => "Emergency department"
            2 => "Inflammatory syndrome"
            3 => "Kawasaki disease"
            4 => "Pediatrics"
            5 => "SARS-CoV-2"
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    "resumen" => array:1 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Multisystem inflammatory syndrome in children &#40;MIS-C&#41; associated with coronavirus disease &#40;COVID-19&#41; is a rare and challenging diagnosis requiring early treatment&#46; The diagnostic criteria involve clinical&#44; laboratory&#44; and complementary tests&#46; This review aims to draw pediatrician attention to this diagnosis&#44; suggesting early treatment strategies&#44; and proposing a pediatric emergency care flowchart&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Sources</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The PubMed&#47;MEDLINE&#47;WHO COVID-19 databases were reviewed for original and review articles&#44; systematic reviews&#44; meta-analyses&#44; case series&#44; and recommendations from medical societies and health organizations published through July 3&#44; 2020&#46; The reference lists of the selected articles were manually searched to identify any additional articles&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Summary of the findings</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">COVID-19 infection is less severe in children than in adults&#44; but can present as MIS-C&#44; even in patients without comorbidities&#46; There is evidence of an exacerbated inflammatory response with potential systemic injury&#44; and it may present with aspects similar to those of Kawasaki disease&#44; toxic shock syndrome&#44; and macrophage activation syndrome&#46; MIS-C can develop weeks after COVID-19 infection&#44; suggesting an immunomediated cause&#46; The most frequent clinical manifestations include fever&#44; gastrointestinal symptoms&#44; rash&#44; mucous membrane changes&#44; and cardiac dysfunction&#46; Elevated inflammatory markers&#44; lymphopenia&#44; and coagulopathy are common laboratory findings&#46; Supportive treatment and early immunomodulation can control the intense inflammatory response and reduce complications and mortality&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">MIS-C associated with COVID-19 is serious&#44; rare&#44; and potentially fatal&#46; The emergency department pediatrician must recognize and treat it early using immunomodulatory strategies to reduce systemic injury&#46; Further studies are needed to identify the disease pathogenesis and establish the most appropriate treatment&#46;</p></span>"
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            "apendice" => "<p id="par0186" class="elsevierStylePara elsevierViewall">The following is Supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "titulo" => "Supplementary data"
            "identificador" => "sec0082"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Interrelationship between the four plasma mediator systems triggered by the activation of factor XII &#40;Hageman factor&#41;&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Kumar et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">COVID 19 disease and MIS-C related to COVID-19&#46; The figure illustrates 4 escalating progressive phases of the disease&#44; according to evolution&#44; severity&#44; clinical signs and symptoms&#44; infectious vs inflammatory host response&#44; diagnosis tests and lab and imaging findings&#46; RT-PCR&#44; reverse transcription-polymerase chain reaction&#59; PCT&#44; procalcitonin&#59; CRP&#44; C-reactive protein&#59; TG&#44; triglycerides&#59; CT&#44; computed tomography&#59; ECHO&#44; echocardiography&#59; EKG&#44; electrocardiogram&#59; EEG&#44; electroencephalography&#59; IL&#44; interleukin&#59; CK&#44; creatine kinase&#59; LDH&#44; lactate dehydrogenase&#59; IgG&#44; immunoglobulin G&#59; BNP&#44; B-type natriuretic peptide&#59; Na&#44; natrium&#59; NK&#44; natural killer&#59; WBC&#44; white blood count&#59; ESR&#44; erythrocyte sedimentation rate&#59; BUN&#44; blood urea nitrogen&#59; C&#44; creatinine&#59; SARS CoV-2&#44; severe acute respiratory syndrome coronavirus 2&#59; MIS-C&#44; multisystem inflammatory syndrome in children and adolescents&#59; US&#44; ultrasound&#46;</p>"
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          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">SIRS&#44; systemic inflammatory response syndrome&#44; HLH&#44; hematophagocytic lymphohistiocytosis&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Castillo and Carcillo&#44; with modifications&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Hematophagocytic lymphohistiocytosis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sepsis&#47;SIRS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Molecular diagnosis&#58; present&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Molecular diagnosis&#58; absent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Five of the following eight criteria&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Fever&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t">Splenomegaly&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Visceromegaly&#43;&#47;&#8722;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Cytopenia of two of three lineages&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Cytopenia of two of three lineages&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Hgb &#60;9 g&#47;L&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Hgb &#60;9 g&#47;L&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Platelets 100<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Platelets 100<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Neutrophils &#60;1<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Neutrophils &#60;1<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Hypertriglyiceridemia &#40;triglycerides &#62;265 mg&#47;dL&#41; or hyperfibrinogenemia &#60;1&#46;5 g&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">Hypertriglyceridemia &#40;triglycerides &#62;265 mg&#47;dL&#41; or hyperfibrinogenemia &#60;1&#46;5 g&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t">Hemophagocytosis in bone marrow&#44; spleen or lymph nodes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hemophagocytosis in bone marrow&#44; spleen or lymph nodes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ferritin &#8805;500<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ferritin &#8805;500<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Low or absent NK cell activity &#40;according to local laboratory reference&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Low or absent NK cell activity &#40;according to local laboratory reference&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soluble CD 25 &#40;soluble IL2 receptor&#41; &#62;2400 U&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soluble CD 25 &#40;soluble IL2 receptor&#41; &#62;2400 U&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2547175.png"
              ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Diagnostic criteria of HLH and clinical and laboratory manifestations of sepsis&#47;SIRS&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">ECHO&#44; echocardiography&#59; NT-proBNP&#44; N-terminal pro-B-type natriuretic peptide&#59; PT&#44; prothrombin time&#59; APTT&#44; activated partial thromboplastin time&#59; ESR&#44; erythrocyte sedimentation rate&#59; CRP&#44; C-reactive protein&#59; RT-PCR&#44; reverse transcription &#8211; polymerase chain reaction&#59; CPK&#44; creatine phosphokinase&#59; LDH&#44; lactate dehydrogenase&#59; IL&#44; interleukin&#59; MIS-C&#44; multisystem inflammatory syndrome in children&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Whittaker et al&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> with modifications&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">World Health Organization<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Royal College of Paediatrics and Child Health &#40;UK&#41;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Centers for Disease Control and Prevention &#40;USA&#41;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Denomination&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pediatric multisystem inflammatory syndrome temporally associated with COVID-19&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multisystem inflammatory syndrome in children &#40;MIS-C&#41; associated with coronavirus disease 2019 &#40;COVID-19&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;19 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;21 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;3 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805;38&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#59; persistent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever &#62;38&#46;0 for &#8805;24 h or reports of subjective fever lasting &#8805;24 h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clinical findings&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">AND</span> two of the following five&#58;1&#46; Rash or bilateral nonpurulent conjunctivitis or mucocutaneous inflammation signs &#40;oral&#44; hands&#44; or feet&#41;&#46;2&#46; Hypotension or shock&#46;3&#46; Acute gastrointestinal problems &#40;diarrhea&#44; vomiting&#44; or abdominal pain&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evidence of single or multiorgan dysfunction &#40;shock&#44; cardiac&#44; respiratory&#44; gastrointestinal&#44; or neurological disorder&#44; kidney&#41;&#46;Most patients hypotension and oxygen supplementary needing&#46;Some patients&#58; abdominal pain&#44; confusion&#44; conjunctivitis&#44; cough&#44; diarrhea&#44; headache&#44; edema&#44; lymphadenomegaly&#44; changes in mucous membranes&#44; cervical rash&#44; respiratory symptoms&#44; odynophagia&#44; hand and foot edema&#44; syncope and vomiting&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evidence of inflammation&#44; and evidence of clinically severe illness requiring hospitalization&#44; with multisystem &#40;&#62;2&#41; organ involvement &#40;cardiac&#44; kidney&#44; respiratory&#44; hematologic&#44; gastrointestinal&#44; dermatologic&#44; or neurological&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Laboratory changes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46; Features of myocardial dysfunction&#44; pericarditis&#44; valvulitis&#44; or coronary abnormalities &#40;including ECHO findings or elevated troponin&#47;NT-proBNP&#41;&#46;5&#46; Evidence of coagulopathy &#40;by PT&#44; APTT&#44; elevated D-dimers&#41;&#46;<span class="elsevierStyleBold">AND</span> Elevated markers of inflammation such as ESR&#44; CRP&#44; or procalcitonin&#46;<span class="elsevierStyleBold">AND</span> No other obvious microbial cause of inflammation&#44; including bacterial sepsis&#44; staphylococcal or treptococcal shock syndromes&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inflammation signs&#46;All patients&#58; elevated CRP&#44; ferritin and D-Dimer&#44; abnormal fibrinogen&#44; hypoalbuminemia and neutrophilia&#46;Some patients&#58; anemia&#44; kidney failure&#44; coagulopathy&#44; neutrophilia&#44; proteinuria&#44; increased CPK&#44; LDH&#44; troponin&#44; transaminases&#44; triglycerides&#44; thrombocytopenia&#44; increased IL-6 &#40;if available&#41; and IL-10 &#40;if available&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Laboratory evidence including&#44; but not limited to&#44; &#8805;1 of the following&#58; an elevated CRP level&#44; ESR&#44; fibrinogen&#44; procalcitonin&#44; D-dimer&#44; ferritin&#44; lactic acid dehydrogenase&#44; or IL-6&#59; elevated neutrophils&#59; reduced lymphocytes&#59; and low albumin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evidence of SARS-CoV-2 infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">AND</span> Evidence of COVID-19 &#40;RT-PCR&#44; antigen test&#44; or serology positive&#41;&#44; or likely contact with patients with COVID-19&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SARS-CoV-2 PCR test results may be positive or negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">AND</span> Positive for current or recent SARS-CoV-2 infection by RT-PCR&#44; serology&#44; or antigen test&#59; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Exclusion criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Another obvious cause of infection or inflammation&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Exclusion of any other microbial cause&#44; including bacterial sepsis&#44; staphylococcal or streptococcal shock syndromes&#44; infections associated with myocarditis such as enterovirus &#40;waiting for results of these investigations should not delay seeking expert advice&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">AND</span> No alternative plausible diagnoses&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Considerations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Consider this syndrome in children with features of typical or atypical Kawasaki disease or toxic shock syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Include children fulfilling full or partial criteria for Kawasaki disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Some individuals may meet the full or partial criteria for Kawasaki disease&#44; but should be reported if they meet the case definition for MIS-C&#46;Consider MIS-C in any pediatric death with evidence of SARS-CoV-2 infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Case definitions for multisystem inflammatory syndrome during the COVID-19 pandemic&#46;</p>"
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      4 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
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            "identificador" => "at3"
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">RT-PCR&#44; reverse transcription &#8211; polymerase chain reaction&#59; PCT&#44; procalcitonin&#59; CRP&#44; C-reactive protein&#59; TG&#44; triglycerides&#59; CT&#44; computed tomography&#59; ECHO&#44; echocardiography&#59; EKG&#44; electrocardiogram&#59; EEG&#44; electroencephalography&#59; IL&#44; interleukin&#59; CK&#44; creatine kinase&#59; LDH&#44; lactate dehydrogenase&#59; IgG&#44; immunoglobulin G&#59; BNP&#44; B-type natriuretic peptide&#59; Na&#44; natrium&#59; NK&#44; natural killer&#59; ESR&#44; erythrocyte sedimentation rate&#59; SARS-CoV-2&#44; severe acute respiratory syndrome coronavirus 2&#59; MIS-C&#44; multisystem inflammatory disorder in children and adolescents&#59; INR&#44; international normalized ratio&#59; LV&#44; left ventricular&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Author&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Symptoms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SARS-CoV-2 detection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Laboratory tests&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Imaging findings&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Riphagen et al&#46;United Kingdom<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#8211;14 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Unrelenting fever&#44; rash&#44; conjunctivitis&#44; peripheral edema&#44; extremity pain&#44; gastrointestinal symptoms&#44; refractory shock&#44; pleural and pericardial effusions and ascitic No significant respiratory involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">RT-PCR</span> not detected<span class="elsevierStyleBold">Serology</span> not specified&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8593; CRP&#8593; PCT&#8593; ferritin&#8593; triglycerides&#8593; D-dimerNegative blood culturesOne positive RT-PCR enterovirus&#47;adenovirus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">X-Ray&#47;CT</span>&#58;Lung consolidations&#44; pleural effusion&#44; ascites&#44; ileitis<span class="elsevierStyleBold">ECHO and EKG</span>&#58; non-specific EKG&#44; echobrightcoronary vessels giant coronary aneurysm&#44; arrhythmia&#44; myocardial dysfunction&#44; ventricular dilatation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Whittaker et al&#46;United Kingdom and USA<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#8211;14 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&#44; sore throat&#44; headache&#44; vomiting&#44; abdominal pain&#44; and diarrhea Rash&#44; conjunctival injection&#44; lymphadenopathy&#44; mucus membrane alterations and red cracked lips&#44; swollen hands and feet&#44; acute kidney injury and shock&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">RT-PCR</span> detected &#40;26&#37;&#41;<span class="elsevierStyleBold">Serology</span> IgG detected &#40;87&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8593; CRP and neutrophil counts&#8595; albumin and lymphocyte counts&#8593; troponin and BNP concentrations compared with those without shock&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">ECHO and EKG</span>&#58; non-specific EKG myocardial dysfunction&#44; arrhythmia&#44; coronary abnormalities such as aneurysms and giant aneurysms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Toubiana et al&#46;France &#40;Paris&#41;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#8211;16 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Recent history of headache&#44; cough&#44; coryza&#44; fever&#44; anosmia&#46; ageusia Polymorphous skin rash&#44; changes to the lips&#47;oral cavity&#44; conjunctival injection&#44; gastrointestinal symptoms &#40;abdominal pain&#44; vomiting&#44; diarrhea&#41;&#44; peritoneal effusion&#44; irritability&#44; headaches&#44; confusion&#47;meningeal irritation&#46; Myocarditis&#44; hypotensive shock&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">RT-PCR</span> detected &#40;38&#37;&#41;<span class="elsevierStyleBold">Serology</span> IgG detected &#40;90&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8593; CRP&#44; PCT&#44; lipase&#44; D-dimer&#44; troponin&#44; and BNP&#8595; albumin&#8595; lymphocytes and platelets count&#59; neutrophil count &#8593;&#8593; alanine transaminasesand &#947;-glutamyltransferase&#8593; IL-6&#8595; NaAcute kidney injuryAnemiaNo other pathogen was identified&#44; except one serology suggestive of recent Epstein-Barr virus infectionCerebrospinal fluid pleocytosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">X Ray&#47;CT&#58;</span>Ground glass opacities&#44; local patchy shadowing&#44; interstitial abnormalities<span class="elsevierStyleBold">ECHO and EKG&#58;</span>Increased QT interval&#44; arrhythmias&#44; signs of ischemia&#44; pericardial effusions&#44; myocardial dysfunctionCoronary artery abnormalities&#44; such as increased visibility and dilations&#46;No coronary aneurysms identified&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Belhadjer et al&#46;France and Switzerland<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2-16 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&#44; asthenia &#40;100&#37;&#41;Abdominal pain&#44; vomiting&#44; diarrhea &#40;80&#37;&#41;&#44; respiratory distress &#40;65&#37;&#41;&#44; skin rash&#44; cheilitis&#44; cervical adenopathy&#44; meningism&#44; chest pain&#44; heart failure&#44; cardiogenic shock&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">RT-PCR</span> detected &#40;40&#37;&#41;<span class="elsevierStyleBold">Serology</span> IgG detected &#40;86&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8593; CRP&#44; PCT&#44; D-dimer&#44; troponin&#44; and BNP&#8593; leukocytes and neutrophils&#8593; IL-6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">ECHO and EKG</span>&#58;Unspecific EKG&#44; signs of ischemia&#8595; LV ejection fraction&#44; hypokinesis&#44; pericardial effusion&#44; coronary arteries dilatationNo coronary aneurysm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Verdoni et al&#46;Italy &#40;Bergamo&#41;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#8211;16 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non-exudative conjunctivitis&#44; alterations of the lips or oral cavity&#44; polymorphic rash&#44; lymphadenopathy&#44; diarrhea&#44; coronary aneurysm&#44; pericardial effusion&#44; meningeal signs&#44; hypotension&#44; and clinical signs of hypoperfusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">RT-PCR</span> detected &#40;20&#37;&#41;<span class="elsevierStyleBold">Serology</span> IgG detected &#40;80&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8593; CRP&#44; ferritin&#44; triglycerides&#44; transaminases&#44; D-dimer&#44; ESR&#44; and fibrinogen&#8595; Na and albumin&#8595; lymphocytes and platelets count&#8593; leukocytes and neutrophils&#8593; IL-6&#44; NK&#8593; CK&#44; troponin&#44; and BNPNo other pathogen was identified&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">ECHO</span>&#58; coronary aneurysm&#44; &#8595; ejection fraction&#44; valve regurgitation&#44; pericardial effusion<span class="elsevierStyleBold">X-ray</span>&#58; pneumonia&#44; minimal mono or bilateral infiltrates<span class="elsevierStyleBold">CT&#58;</span> bibasilar pulmonary thickening<span class="elsevierStyleBold">EEG</span>&#58; slow wave pattern&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Feldstein et al&#46;USA<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">186&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;3 years &#40;average&#41;1&#8211;14 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&#44; rash&#44; conjunctivitis&#44; oral mucosal alterations&#44; peripheral extremity changes&#44; lymphadenopathy&#44; abdominal pain&#44; tachycardia&#44; vomiting&#44; diarrhea&#44; cough&#44; dyspnea&#44; arthralgia&#44; myalgia&#44; myocarditis&#44; pericarditis&#44; arrhythmias&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">RT-PCR</span> detected &#40;77&#37;&#41;<span class="elsevierStyleBold">Serology</span> Ig detected &#40;88&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8593; CRP&#44; ferritin&#44; D-dimer&#44; fibrinogen&#44; troponin&#44; and BNP&#44; ESR&#44; INR&#44; ALT&#8595; hemoglobin and platelets&#8595; albuminLymphocytopeniaNeutrophilia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">ECHO&#58;</span> Coronary-artery aneurysms&#44; pericarditis&#44; pericardial effusion&#44; arrhythmia&#44; &#8595; ejection fraction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dufort et al&#46;USA<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0-20 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&#44; chills&#44; tachycardia&#44; abdominal pain&#44; vomiting&#44; diarrhea&#44; inflammation or enlargement of the appendix&#47;gallbladder&#44; hepatomegaly and&#47;or splenomegaly&#44; conjunctivitis&#44; oral mucosal alterations&#44; rash&#44; headache&#44; lymphadenopathy&#44; cough&#44; sore throat&#44; wheezing&#44; myocarditis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">RT-PCR</span> detected &#40;51&#37;&#41;<span class="elsevierStyleBold">Serology</span> IgG detected &#40;99&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8593; CPR&#44; PCT&#44; ferritin&#44; D-dimer&#44; fibrinogen&#44; troponin&#44; and BNP&#8593; IL-6&#8595; albumin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">ECHO</span>&#58; ventricular dysfunction&#44; pericardial effusion&#44; and coronary-artery aneurysm<span class="elsevierStyleBold">X Ray&#47;CT</span>&#58; opacity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Capone et al&#46; USA &#40;New York&#41;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;6 years &#40;average&#41;5&#46;5&#8211;12&#46;6 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&#44; clinical signs of complete or incomplete Kawasaki disease&#44; abdominal pain&#44; vomiting&#44; diarrhea&#44; headache&#44; irritability&#44; lethargy&#44; cough&#44; congestion&#44; dyspnea&#44; sore throat&#44; shock with cardiac dysfunction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">RT-PCR</span> detected &#40;9&#37;&#41;<span class="elsevierStyleBold">Serology</span> IgG detected &#40;91&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8593; CPR&#44; PCT&#44; ferritin&#44; transaminases&#44; D-dimer&#44; and fibrinogen&#8595; albumin&#8595; lymphocytes and platelets count&#59; normal neutrophil count or &#8593;&#8595; Na&#8593; LDH&#44; INR&#44; troponin&#44; and BNPAcute kidney injuryAnemiaNo other pathogen was identifiedOne positive RT-PCR influenza&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">ECHO</span>&#58; coronary abnormality&#44; dysfunction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Imaging and laboratory findings of children and adolescents presenting with SARS-CoV-2-related symptoms and signs of MIS-C&#44; according to the authors&#46;</p>"
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        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">ICU&#44; intensive care unit&#59; ECMO&#44; extracorporeal membrane oxygenation&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Author&#47;country&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type of study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age &#40;median&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical evolution&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Grimaud et al&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a>France&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Atypical Kawasaki and severe inflammatory multisystem disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;9&#8211;15 years&#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; ICU100&#37; myocarditis100&#37; cardiogenic shock95&#37; vasoactive support40&#37; mechanical ventilationThere were no deaths and all recovered left ventricular function&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; IGIV &#40;2g&#47;kg&#41;10&#37; corticosteroids5&#37; anakinra5&#37; tocilizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Toubiana et al&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a>France&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kawasaki-like multisystem inflammatory syndrome in children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;7&#8211;16&#46;6 years&#40;7&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">81&#37; ICU76&#37; myocarditis71&#37; vasoactive support52&#37; mechanical ventilationAll patients were discharged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; IGIV &#40;2g&#47;kg&#41;24&#37; 2nd IGIV dose48&#37; corticosteroids100&#37; Aspirin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kyotos et al&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">64</span></a>USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multisystem inflammatory syndrome in children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#8211;14 years&#40;7&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; ICU100&#37; cardiogenic shock83&#37; vasoactive support50&#37; mechanical ventilationAll were discharged with recovery of cardiac function&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; IGIV &#40;2g&#47;kg&#41;100&#37; corticosteroids2 patients 2nd IGIV dose1 patient anakinra and aspirin1 patient aspirin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Riphagen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>United Kingdom&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multisystem inflammatory syndrome in children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#8211;14 years&#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; ICU100&#37; vasoactive support87&#46;5&#37; mechanical ventilation87&#46;5&#37; myocardial dysfunction12&#46;5&#37; ECMOThere was one death&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; IGIV &#40;2g&#47;kg&#41;50&#37; corticosteroids25&#37; aspirin12&#46;5&#37; infliximab12&#46;5&#37; therapeutic heparin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Belhadjer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a>France&#44; Switzerland&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multisystem inflammatory syndrome in children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8211;16 years&#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; ICU100&#37; left ventricular dysfunction80&#37; inotropic support62&#37; mechanical ventilation28&#37; ECMOThere were no deaths&#46;Left ventricular function was restored in 25&#47;35 patients&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&#37; IGIV34&#37; corticosteroid65&#37; heparin3&#37; anakinra1 patient 2nd IGIV doseAuthors suggest that treatment with IVIG may be associated with ventricular recovery&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Verdoni et al&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a>Italy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Observational cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kawasaki disease shock syndrome&#44; or severe Kawasaki-like disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;9&#8211;16 years&#40;7&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#37; myocardial dysfunction20&#37; inotropic support&#46;0&#37; mechanical ventilationAll patients were discharged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; IGIV &#40;2g&#47;kg&#41;80&#37; corticosteroid20&#37; aspirin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cheung et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multisystem inflammatory syndrome in children and adolescents&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;8&#8211;16 years&#40;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">88&#37; ICU59&#37; vasoactive support0&#37; mechanical ventilationThere were no deaths&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76&#37; IGIV &#40;2g-4g&#47;kg&#41;92&#37; corticosteroid24&#37; aspirin6&#37; tocilizumab59&#37; prophylactic enoxaparin6&#37; therapeutic enoxaparin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Whittaker et al&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a>England&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pediatric inflammatory multisystem syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;7&#8211;14 years&#40;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#37; cardiogenic shock50&#37; vasoactive support43&#37; mechanical ventilation5&#37; ECMOThere were two deaths&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&#37; IGIV64&#37; corticosteroid14&#37; infliximab5&#37; anakinraAssociation of two agents in 60&#37; of patients and three agents in 16&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Panupattanapong et al&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">61</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Review&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kawasaki-like syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Emerging phenotypes are a combination of typical or atypical Kawasaki disease&#44; Kawasaki shock syndrome&#44; toxic shock syndrome&#44; macrophage activation syndrome and hemophagocytic lymphohistiocytosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with criteria for Kawasaki disease&#44; atypical Kawasaki disease&#44; or coronary changes should receive IVIG &#40;2G&#47;kg&#41; and high doses of Aspirin&#46; If the hyperinflammatory component is prominent&#44; consider using corticosteroids&#44; tocilizumab&#44; or anakinra&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Miller et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a>USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multisystem inflammatory syndrome in children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 months&#8211;20 years&#40;7&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#37;&#58; vasoactive support50&#37;&#58; cardiac abnormality1 patient&#58; mechanical ventilationThere were no deaths&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">82&#37; IGIV &#40;2g&#47;kg&#41;95&#37; corticosteroids18&#37; anakinra90&#37; Anticoagulation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Feldstein et al&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multisystem inflammatory syndrome in children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">186&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;3&#8211;12&#46;5 years&#40;8&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#37; vasoactive support20&#37; mechanical ventilation8 &#40;4&#37;&#41; ECMOThere were 4 deaths &#40;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77&#37; IGIV &#40;2g&#47;kg&#41;49&#37; corticosteroids13&#37; anakinra8&#37; IIL-6 inhibitor47&#37; Anticoagulation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dufort et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multisystem inflammatory syndrome in children&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Under 21 years31&#37; &#40;0-5 years&#41;42&#37; &#40;6-12 years&#41;25&#37; &#40;13-20 years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#37; vasoactive support10&#37; mechanical ventilation53&#37; myocarditis4 &#40;4&#37;&#41; ECMOThere were 2 deaths &#40;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#37; IGIV &#40;2g&#47;kg&#41;64&#37; corticosteroids48&#37; IVIG and corticosteroids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">European Center for Disease Prevention and Control<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a>Europe and North America&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Guideline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pediatric multisysteminflammatory syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">322&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Literature review with clinical description&#44; risk factors&#44; severity&#44; treatment and communication of the disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">If Kawasaki&#39;s disease is part of the differential diagnosis&#44; the use of IVIG has been the predominant approach&#46;Corticosteroids and anti-TNF monoclonal antibodies have also been used&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Capone et al&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a>USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case series&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pediatric multisystem inflammatory syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;2&#8211;17 years&#40;8&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79&#37; ICU76&#37; vasoactive support58&#37; myocardial dysfunction48&#37; coronary abnormality64&#37; complete Kawasaki diseaseThere were no deaths&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37; IGIV33&#37; 2nd dose IVIG70&#37; corticosteroid88&#37; aspirin12&#37; anakinra9&#37; tocilizumab3&#37; infliximab42&#37; enoxaparin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Giglia et al&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">82</span></a> and Monagle et al&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">86</span></a></p><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">SC&#44; subcutaneously&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Prophylaxis dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Under 2 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;75 mg&#47;kg&#47;dose SC 12&#47;12h or1&#46;5 mg&#47;kg&#47;dose SC every 24h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;7 mg&#47;kg SC every 12h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Over 2 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5 mg&#47;kg&#47;dose SC 12&#47;12h or1 mg&#47;kg&#47;dose SC every 24h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;0 mg&#47;kg SC every 12h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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ISSN: 00217557
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Jornal de Pediatria (English Edition)
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