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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introdu&#231;&#227;o</span><p id="par0010" class="elsevierStylePara elsevierViewall">O Brasil se tornou o epicentro da infec&#231;&#227;o pelo novo coronav&#237;rus &#40;SARS&#8208;CoV&#8208;2&#41; na Am&#233;rica do Sul e o segundo pa&#237;s com o maior n&#250;mero de casos e mortes no mundo&#46; A COVID&#8208;19&#44; como essa doen&#231;a foi chamada pela Organiza&#231;&#227;o Mundial da Sa&#250;de&#44; ainda representa um desafio na popula&#231;&#227;o pedi&#225;trica&#44; embora o n&#250;mero e a gravidade dos casos sejam menores quando comparados &#224; popula&#231;&#227;o adulta&#46; Dados de v&#225;rios pa&#237;ses mostram que crian&#231;as e adolescentes foram respons&#225;veis por menos de 2&#37; dos casos sintom&#225;ticos&#44; com taxas de hospitaliza&#231;&#227;o &#40;0&#44;6&#8208;20&#37;&#41; e mortalidade &#40;0&#8208;4&#37;&#41; significativamente menores do que nos adultos&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">1&#8211;5</span></a> Beb&#234;s e crian&#231;as com doen&#231;as cr&#244;nicas pr&#233;vias representam a popula&#231;&#227;o pedi&#225;trica mais vulner&#225;vel&#44; com maior gravidade&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">1&#44;2&#44;4&#44;5</span></a> Recentemente&#44; v&#225;rios pa&#237;ses relataram casos de uma s&#237;ndrome inflamat&#243;ria multissist&#234;mica &#40;MIC&#44; do ingl&#234;s <span class="elsevierStyleItalic">multisystemic inflammatory syndrome</span>&#41; em crian&#231;as &#40;MIS&#8208;C&#41; temporariamente associada &#224; COVID&#8208;19&#46; Essa s&#237;ndrome &#233; caracterizada por febre prolongada&#44; sintomas gastrointestinais e marcadores inflamat&#243;rios alterados&#44; associados a sinais de disfun&#231;&#227;o org&#226;nica&#44; insufici&#234;ncia card&#237;aca aguda&#44; doen&#231;a de Kawasaki &#40;completa ou n&#227;o&#41; ou s&#237;ndrome do choque t&#243;xico&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">6&#8211;8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">O relato da experi&#234;ncia latino&#8208;americana com a COVID&#8208;19 em pediatria ainda &#233; bastante limitado&#44; principalmente em rela&#231;&#227;o a crian&#231;as internadas em unidades de terapia intensiva&#46; Este estudo tem como objetivo descrever as caracter&#237;sticas cl&#237;nicas de uma coorte de crian&#231;as e adolescentes internados em Unidades de Terapia Intensiva Pedi&#225;tricas &#40;UTIPs&#41; no Brasil&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material e m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Desenho do estudo&#44; sele&#231;&#227;o de pacientes e local do estudo</span><p id="par0025" class="elsevierStylePara elsevierViewall">Este &#233; um estudo prospectivo&#44; multic&#234;ntrico&#44; feito em 19 UTIPs associadas &#224; Rede Brasileira de Pesquisa em Terapia Intensiva Pedi&#225;trica &#40;<span class="elsevierStyleItalic">Brazilian Research Network in Pediatric Intensive Car</span>e&#44; BRnet&#8208;PIC&#41;&#46; Pacientes pedi&#225;tricos &#40;um m&#234;s a 19 anos&#41; com COVID&#8208;19 confirmada foram inclu&#237;dos consecutivamente entre 1&#176; de mar&#231;o e 31 de maio de 2020&#44; ap&#243;s a obten&#231;&#227;o do consentimento informado&#46; O estudo foi aprovado pelos Comit&#234;s de &#201;tica em pesquisa de todas as institui&#231;&#245;es&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Diagn&#243;stico e coleta de dados</span><p id="par0030" class="elsevierStylePara elsevierViewall">O diagn&#243;stico de COVID&#8208;19 foi confirmado pelo ensaio de rea&#231;&#227;o em cadeia da polimerase com transcri&#231;&#227;o reversa &#40;RT&#8208;PCR&#41; a partir de <span class="elsevierStyleItalic">swabs</span> oro&#47;nasofar&#237;ngeos ou aspirados traqueais e quando fora do per&#237;odo de positividade para RT&#8208;PCR&#44; foram usados anticorpos IgM e&#47;ou IgG positivos contra SARS&#8208;CoV&#8208;2&#46; Os dados demogr&#225;ficos&#44; epidemiol&#243;gicos&#44; cl&#237;nicos e de desfecho dos pacientes foram coletados prospectivamente&#44; em formul&#225;rios padronizados de relato de caso &#40;REDCap&#44; <span class="elsevierStyleItalic">Vanderbilt University</span>&#44; EUA&#41;&#46; Os pacientes com MIS e n&#227;o MIS foram comparados&#44; de acordo com a presen&#231;a de comorbidades&#44; idade inferior a um ano e necessidade de ventila&#231;&#227;o mec&#226;nica invasiva &#40;VMI&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Processamento de dados e an&#225;lise estat&#237;stica</span><p id="par0035" class="elsevierStylePara elsevierViewall">As vari&#225;veis categ&#243;ricas foram descritas como frequ&#234;ncias e porcentagens e as vari&#225;veis cont&#237;nuas como medianas e intervalos interquartis &#40;IIQs&#41;&#46; As compara&#231;&#245;es entre os grupos foram feitas pelo teste do qui&#8208;quadrado ou exato de Fisher para vari&#225;veis categ&#243;ricas e teste de Mann&#8208;Whitney para vari&#225;veis cont&#237;nuas&#46; Um modelo de regress&#227;o log&#237;stica multivari&#225;vel foi usado para avaliar a associa&#231;&#227;o das covari&#225;veis com idade inferior a um ano&#44; sexo&#44; etnia e presen&#231;a de comorbidades com as formas mais graves da doen&#231;a&#44; caracterizadas pela necessidade de VMI&#46; Foram estabelecidos um n&#237;vel de signific&#226;ncia de 5&#37; &#40;bicaudal&#41; e intervalos de confian&#231;a de 95&#37;&#46; O <span class="elsevierStyleItalic">software</span> R&#44; vers&#227;o 3&#46;6&#46;1 &#40;R Foundation&#44; Viena&#44; &#193;ustria&#41;&#44; foi usado para a an&#225;lise estat&#237;stica&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Resultados</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Caracter&#237;sticas demogr&#225;ficas e epidemiol&#243;gicas</span><p id="par0040" class="elsevierStylePara elsevierViewall">Foram inclu&#237;dos 79 pacientes &#40;10 com MIS&#41;&#46; 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47 pacientes &#40;60&#37;&#41; apresentavam sintomas respirat&#243;rios&#44; a maioria pneumonia ou bronquiolite &#40;70&#37;&#41;&#44; 10 &#40;13&#37;&#41; apresentavam MIS e 60&#37; apresentavam uma condi&#231;&#227;o semelhante &#224; doen&#231;a de Kawasaki&#46; Os outros 22 &#40;28&#37;&#41; apresentavam principalmente sintomas gastrointestinais e neurol&#243;gicos &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46; A mediana do tempo dos sintomas antes da hospitaliza&#231;&#227;o foi de cinco dias no grupo n&#227;o MIS e dois dias no grupo MIS&#46; Os sinais e sintomas mais comuns na apresenta&#231;&#227;o foram febre &#40;76&#37;&#41;&#44; tosse &#40;51&#37;&#41; e taquipneia &#40;50&#37;&#41;&#46; Entretanto&#44; outros achados tamb&#233;m foram prevalentes &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46; No grupo MIS&#44; sintomas graves como taquipneia &#40;60&#37;&#41;&#44; baixa SpO<span class="elsevierStyleInf">2</span> &#40;40&#37;&#41;&#44; prostra&#231;&#227;o &#40;60&#37;&#41;&#44; gem&#234;ncia &#40;30&#37;&#41;&#44; hipotens&#227;o &#40;20&#37;&#41;&#44; batimento de asa nasal &#40;20&#37;&#41; e cianose &#40;10&#37;&#41;&#44; bem como sintomas gastrointestinais &#40;40&#8208;60&#37;&#41;&#44; foram mais frequentes do que no grupo n&#227;o MIS &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Confirma&#231;&#227;o do diagn&#243;stico&#44; achados laboratoriais e radiol&#243;gicos</span><p id="par0050" class="elsevierStylePara elsevierViewall">O diagn&#243;stico foi confirmado por RT&#8208;PCR em 72 pacientes &#40;todos os 79 testados&#44; 91&#37; positivos&#41;&#46; Os demais tiveram o diagn&#243;stico confirmado pela detec&#231;&#227;o de anticorpos IgM e&#47;ou IgG &#40;cinco no grupo MIS&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46; Houve codetec&#231;&#227;o com outros v&#237;rus em 15&#37; dos testados &#40;dois v&#237;rus sincicial respirat&#243;rio&#44; um rinov&#237;rus humano e um uma associa&#231;&#227;o de Parainfluenza 4 com <span class="elsevierStyleItalic">Bordetella pertussis</span>&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Linfopenia foi observada em 36&#37; dos pacientes no grupo n&#227;o MIS &#40;MIS&#44; 50&#37;&#41;&#46; A prote&#237;na C reativa &#40;PCR&#41; foi de 3<span class="elsevierStyleHsp" style=""></span>mg&#47;dL ou superior em 50&#37; dos 63 pacientes do grupo n&#227;o MIS&#44; em compara&#231;&#227;o com 10<span class="elsevierStyleHsp" style=""></span>mg&#47;dL ou superior em 50&#37; dos 10 pacientes do grupo MIS&#46; A velocidade de hemossedimenta&#231;&#227;o &#40;VHS&#41;&#44; a desidrogenase l&#225;ctica &#40;LDH&#41; e o D&#8208;d&#237;mero foram testados em 5&#44; 30 e 22 pacientes&#44; respectivamente&#44; no grupo n&#227;o MIS e quase todos os pacientes no grupo MIS&#46; Eles estavam aumentados em pelo menos 75&#37; de todos os pacientes&#44; mas muito mais altos no grupo MIS&#46; Em contraste&#44; as fun&#231;&#245;es renal e hep&#225;tica foram testadas na maioria dos pacientes e estavam preservadas em pelo menos 75&#37; delas nos dois grupos&#46; A ferritina e a troponina foram testadas em apenas 24 e 17 pacientes&#44; respectivamente&#44; a maioria deles no grupo MIS&#46; A ferritina estava aumentada em pelo menos 50&#37; dos pacientes e foi maior no grupo n&#227;o MIS&#46; A troponina estava elevada em pelo menos 50&#37; dos pacientes do grupo n&#227;o MIS&#44; mas n&#227;o no grupo MIS&#46; Dos outros marcadores de les&#227;o card&#237;aca&#44; a creatinofosfoquinase &#40;CK&#41; apresentou anormalidade em 5 dos 22 pacientes &#40;408&#8208;2&#46;345 U&#47;L&#41; e a creatinofosfoquinase fra&#231;&#227;o MB &#40;CK&#8208;MB&#41; estava elevada em 8 dos 15 pacientes &#40;25 e 89 U&#47;L&#41;&#46; Apenas um desses pacientes estava no grupo MIS &#40;s&#237;ndrome do choque t&#243;xico&#44; CK 1&#46;389 U&#47;L&#44; CK&#8208;MB 28 U&#47;L&#41;&#46; O pept&#237;deo natriur&#233;tico do tipo B &#40;pro&#8208;BNP&#41; estava aumentado em 6 dos 7 &#40;86&#37;&#41; pacientes testados&#44; todos no grupo MIS&#44; com uma mediana de 5&#46;829 &#40;varia&#231;&#227;o de 222&#8208;16&#46;996 pg&#47;mL&#41;&#46; A procalcitonina foi investigada em apenas tr&#234;s pacientes e estava elevada em todos &#40;um no grupo n&#227;o MIS&#44; 0&#44;4 ng&#47;mL&#59; dois no grupo MIS&#58; uma disfun&#231;&#227;o card&#237;aca aguda&#44; 0&#44;37 ng&#47;mL e uma s&#237;ndrome de choque t&#243;xico&#44; 31 ng&#47;mL&#41;&#46; Por fim&#44; a interleucina&#8208;6 foi mensurada em apenas dois pacientes do grupo MIS&#44; ambos com valores muito altos&#44; em um paciente com disfun&#231;&#227;o card&#237;aca aguda &#40;711 pg&#47;mL&#41; e um com s&#237;ndrome de choque t&#243;xico &#40;194 pg&#47;mL&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;</p><p id="par0060" class="elsevierStylePara elsevierViewall">A radiografia de t&#243;rax mostrou anormalidades em 60&#8208;70&#37; dos pacientes nos dois grupos&#44; com predomin&#226;ncia do infiltrado intersticial difuso bilateral &#40;57&#8208;60&#37;&#41;&#46; O derrame pleural estava presente em sete pacientes &#40;43&#37;&#41; no grupo MIS e em apenas tr&#234;s pacientes &#40;9&#37;&#41; no grupo n&#227;o MIS&#46; Trinta e oito pacientes foram submetidos &#224; tomografia computadorizada &#40;TC&#41; de t&#243;rax e opacidades em vidro fosco estavam presentes em 58&#37; no grupo n&#227;o MIS e em apenas 14&#37; no grupo MIS &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Manejo e resultados cl&#237;nicos</span><p id="par0065" class="elsevierStylePara elsevierViewall">Cinquenta e um de todos os pacientes &#40;65&#37;&#41; precisaram de algum tipo de suporte ventilat&#243;rio&#58; 32 &#40;41&#37;&#41; usaram apenas oxigenoterapia&#44; cinco &#40;6&#37;&#41; precisaram apenas de ventila&#231;&#227;o n&#227;o invasiva &#40;VNI&#41; e 14 &#40;18&#37;&#41; necessitaram de VMI&#46; Nos pacientes que necessitaram de VMI&#44; 10 &#40;71&#37;&#41; apresentavam s&#237;ndrome do desconforto respirat&#243;rio agudo &#40;SDRA&#41;&#44; dos quais seis foram classificados como graves&#44; exigiram bloqueio neuromuscular &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;&#44; manobra de recrutamento alveolar &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41; e posi&#231;&#227;o prona intermitente &#40;n &#61; 3&#41; Dois desses pacientes desenvolveram hipertens&#227;o arterial pulmonar&#46; A mediana de dura&#231;&#227;o da VMI foi de 7&#44;5 dias &#40;IIQ 5&#8208;10&#41; e a mediana da press&#227;o expirat&#243;ria final positiva &#40;PEEP&#41; mais alta foi de 9&#44;5 cmH<span class="elsevierStyleInf">2</span>O &#40;IIQ 7&#8208;12&#41;&#46; Um desses casos graves de SDRA estava no grupo MIS &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Antibi&#243;ticos foram usados por 76&#37; de todos os pacientes&#44; oseltamivir em 43&#37; e corticosteroides em 23&#37;&#46; Nenhum paciente recebeu hidroxicloroquina &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46; A mediana do tempo de perman&#234;ncia &#40;TP&#41; na UTIP foi de 5 dias &#40;IIQ 2&#44;2&#8208;10&#41; e a maioria dos pacientes recebeu alta &#40;90&#37;&#41;&#46; As &#250;nicas duas mortes &#40;3&#37; de mortalidade&#41; ocorreram no grupo n&#227;o MIS&#44; ambos os pacientes com comorbidades graves e uso cr&#244;nico de corticosteroides &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46; Um caso era uma menina de 14 anos com doen&#231;a hep&#225;tica cr&#244;nica e o outro&#44; uma menina de um ano com doen&#231;a pulmonar cr&#244;nica e s&#237;ndrome do intestino curto&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Subgrupos espec&#237;ficos</span><p id="par0075" class="elsevierStylePara elsevierViewall">O subgrupo de pacientes com comorbidades era significativamente mais velho &#40;m&#233;dia de idade&#58; 7&#44;5 anos <span class="elsevierStyleItalic">vs</span>&#46; 1&#44;8 ano&#44; p 0&#44;01&#41;&#44; tinha maior necessidade de oxigenoterapia &#40;56&#37; <span class="elsevierStyleItalic">vs</span>&#46; 31&#37;&#44; p 0&#44;05&#41; e VMI &#40;31&#37; <span class="elsevierStyleItalic">vs</span>&#46; 9&#37;&#44; p 0&#44;01&#41; e diagn&#243;stico mais frequente de SDRA &#40;25&#37; <span class="elsevierStyleItalic">vs</span>&#46; 4&#37;&#44; p 0&#44;01&#41;&#44; mas n&#227;o houve diferen&#231;as em rela&#231;&#227;o &#224; dura&#231;&#227;o do suporte respirat&#243;rio e do TP na UTIP&#46; Nos pacientes que necessitaram de VMI&#44; o TP na UTIP foi significativamente maior &#40;12&#44;0 <span class="elsevierStyleItalic">vs</span>&#46; 5&#44;0 dias&#44; p 0&#44;01&#41;&#46; A idade inferior a um ano n&#227;o determinou uma apresenta&#231;&#227;o cl&#237;nica diferente&#46; Nos pacientes com MIS&#44; n&#227;o observamos diferen&#231;as significativas entre os pacientes com comorbidades&#44; idade inferior a um ano e necessidade de VMI &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>a&#41;&#46; Tamb&#233;m comparamos esses tr&#234;s grupos espec&#237;ficos&#44; consideramos apenas pacientes que n&#227;o apresentavam MIS&#44; mas os resultados foram bastante semelhantes &#40;<a class="elsevierStyleCrossRef" href="#sec0080">tabelas S1 e S2&#44; material suplementar</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">A an&#225;lise multivariada mostrou que apenas a presen&#231;a de comorbidades estava significativamente associada &#224; gravidade&#44; representada pela necessidade de VMI &#40;<span class="elsevierStyleItalic">OR</span> ajustado 5&#44;5&#59; IC95&#37; 1&#44;43&#8208;21&#44;12&#59; p 0&#44;01&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>b&#41;&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Discuss&#227;o</span><p id="par0085" class="elsevierStylePara elsevierViewall">Que seja de nosso conhecimento&#44; este &#233; o primeiro estudo prospectivo e multic&#234;ntrico a relatar caracter&#237;sticas e resultados de crian&#231;as com COVID&#8208;19 internadas em UTIPs no Brasil&#44; o atual epicentro da doen&#231;a na Am&#233;rica Latina e o segundo no mundo&#44; depois dos EUA&#46; Embora a maioria das crian&#231;as e adolescentes tenha um curso benigno da doen&#231;a&#44; demonstramos que alguns pacientes podem desenvolver condi&#231;&#245;es cl&#237;nicas agudas graves&#44; especialmente aquelas com comorbidades anteriores&#44; e posteriormente tamb&#233;m apresentam MIS&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Em nossa coorte&#44; embora a mediana de idade fosse de quatro anos e um quarto dos pacientes fosse lactente&#44; 44&#37; eram crian&#231;as em idade escolar&#44; adolescentes e adultos jovens&#44; um percentual superior ao geralmente observado nas UTIPs brasileiras para essa faixa et&#225;ria&#44; geralmente em torno de 25&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">9</span></a> Isso &#233; semelhante ao relatado por um grande estudo europeu<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">10</span></a> e por UTIPs americanas&#44; que relataram uma porcentagem ainda maior de hospitaliza&#231;&#245;es nessa faixa et&#225;ria &#40;70&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">2&#44;11</span></a> N&#227;o observamos uma grande diferen&#231;a entre as medianas das idades dos grupos MIS e n&#227;o MIS&#44; embora nosso n&#250;mero de pacientes com MIS tenha sido pequeno&#46; Quanto ao sexo&#44; n&#227;o houve diferen&#231;as no grupo n&#227;o MIS&#44; enquanto nos pacientes com MIS houve predom&#237;nio masculino de 4&#58;1&#44; diferentemente do relatado por outros autores&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">12&#44;13</span></a> Houve uma pequena predomin&#226;ncia de pacientes de etnia branca &#40;58&#8208;60&#37;&#41;&#44; o que est&#225; em contraste com a predomin&#226;ncia da popula&#231;&#227;o brasileira&#44; que &#233; de 56&#37; de n&#227;o brancos&#46; Entretanto&#44; cerca de metade dos pacientes era de hospitais particulares&#44; acess&#237;veis apenas &#224; popula&#231;&#227;o de renda m&#233;dia e alta&#44; onde os brancos s&#227;o a maioria&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">As comorbidades t&#234;m sido descritas como um importante fator de risco para casos mais graves de COVID&#8208;19 em crian&#231;as&#44; representam entre 50&#8208;80&#37; das admiss&#245;es em UTIP&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">11&#44;14&#44;15</span></a> Embora tiv&#233;ssemos uma porcentagem um pouco menor desses pacientes &#40;41&#37;&#41;&#44; eles eram significativamente mais velhos e tinham uma apresenta&#231;&#227;o significativamente mais grave &#40;mais SDRA&#44; mais suporte ventilat&#243;rio&#44; mais VMI&#41;&#46; O modelo de regress&#227;o log&#237;stica mostrou que as comorbidades estavam independentemente associadas &#224; necessidade de VMI&#44; com um <span class="elsevierStyleItalic">odds ratio</span> ajustado de 5&#44;5 &#91;IC95&#37;&#44; 1&#44;4&#8208;21&#44;1&#41;&#46; Doen&#231;a neuromuscular&#44; doen&#231;a respirat&#243;ria cr&#244;nica e doen&#231;a onco&#8208;hematol&#243;gica foram as comorbidades mais prevalentes em nossa coorte&#44; o que &#233; um pouco diferente de outros relatos em terapia intensiva pedi&#225;trica&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">5&#44;11&#44;14&#44;15</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Somente cerca de 40&#37; dos pacientes tinham hist&#243;rico pr&#233;vio de contato com um caso suspeito&#44; principalmente em casa&#44; o que &#233; semelhante a outros relatos&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">4</span></a> A febre foi o sintoma predominante&#44; seguido por v&#225;rios sinais e sintomas respirat&#243;rios e gastrointestinais&#44; que n&#227;o diferiram do que foi relatado em outros estudos&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">5&#44;10&#44;14&#44;16</span></a> Houve maior preval&#234;ncia de sintomas gastrointestinais no grupo MIS&#44; como diarreia e v&#244;mito com desidrata&#231;&#227;o&#44; o que tamb&#233;m foi observado por outros autores&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">12&#44;13</span></a> O intervalo entre o in&#237;cio dos sintomas e a hospitaliza&#231;&#227;o foi menor no grupo MIS &#40;mediana&#44; 2 <span class="elsevierStyleItalic">vs</span>&#46; 5 dias&#41;&#46; Isso pode ser explicado pelos casos mais graves nesse grupo&#44; alguns deles apresentaram sinais de choque e insufici&#234;ncia cardiorrespirat&#243;ria&#46; Embora a principal s&#237;ndrome cl&#237;nica na hospitaliza&#231;&#227;o fosse geralmente de origem respirat&#243;ria ou gastrointestinal&#44; tivemos 10 pacientes &#40;13&#37;&#41; internados na UTIP por causa da MIS&#46; Esse &#233; um fen&#244;meno novo relacionado &#224; COVID&#8208;19 em crian&#231;as e espera&#8208;se que muitos desses pacientes precisem de acompanhamento na UTIP e tamb&#233;m por outras especialidades pedi&#225;tricas&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">6</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">A maioria dos nossos pacientes teve seu diagn&#243;stico confirmado por RT&#8208;PCR &#40;91&#37;&#41;&#44; mas observamos uma propor&#231;&#227;o maior de resultados negativos no grupo MIS &#40;50&#37; <span class="elsevierStyleItalic">vs</span>&#46; 15&#37;&#41;&#46; Isso &#233; compat&#237;vel com dados anteriores&#44; mostra que a MIS &#233; uma manifesta&#231;&#227;o tardia associada ao COVID&#8208;19&#44; fora da janela de positividade para a RT&#8208;PCR&#46; Nesse grupo&#44; a associa&#231;&#227;o com uma infec&#231;&#227;o por SARS&#8208;CoV&#8208;2 foi observada em metade dos pacientes atrav&#233;s de sorologia positiva&#44; principalmente IgG&#46; Por outro lado&#44; no grupo n&#227;o MIS&#44; uma IgM positiva foi detectada em 80&#37; dos poucos casos nos quais foi medida&#46; A codetec&#231;&#227;o com outros v&#237;rus foi observada em 15&#37; dos pacientes nos quais foi investigada &#40;apenas no grupo n&#227;o MIS&#41;&#44; semelhante a outros estudos da COVID&#8208;19<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">5&#44;10</span></a> e em outras infec&#231;&#245;es graves por v&#237;rus respirat&#243;rios em crian&#231;as&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">17</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">A linfopenia foi observada em geral em 38&#37; dos pacientes &#40;50&#37; no grupo MIS&#41;&#44; o que tamb&#233;m j&#225; foi descrito em outros estudos pedi&#225;tricos da COVID&#8208;19&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">5&#44;14&#44;15&#44;18</span></a> Embora alguns estudos em adultos tenham associado linfopenia a um progn&#243;stico ruim&#44;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">19&#44;20</span></a> isso ainda n&#227;o est&#225; claro na pediatria&#46; Marcadores inflamat&#243;rios&#44; como VHS&#44; PCR&#44; LDH&#44; D&#8208;D&#237;mero&#44; procalcitonina e ferritina&#44; estavam elevados na maioria dos pacientes testados&#44; mas principalmente no grupo MIS&#44; o que est&#225; de acordo com os crit&#233;rios diagn&#243;sticos para essa s&#237;ndrome&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">21&#8211;23</span></a> Em nossa coorte&#44; medimos a troponina&#44; CK e CK&#8208;MB em menos de 20&#37; dos pacientes e encontramos n&#237;veis elevados em pelo menos 50&#37; deles&#46; Esses biomarcadores de les&#245;es card&#237;acas tamb&#233;m foram relatados com n&#237;veis anormais em outros estudos&#44; principalmente em pacientes com algum tipo de insufici&#234;ncia card&#237;aca&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">12&#8211;14</span></a> Outro marcador sens&#237;vel conhecido para detec&#231;&#227;o de insufici&#234;ncia card&#237;aca&#44; o ProBNP&#44; estava elevado em todos os sete pacientes nos quais foi medido no grupo MIS&#44; como tamb&#233;m relatado em outros estudos&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">6&#44;24</span></a> Tamb&#233;m medimos a interleucina&#8208;6 &#40;IL&#8208;6&#41; em dois pacientes do grupo MIS&#44; ambos com disfun&#231;&#227;o card&#237;aca grave e choque e n&#237;veis muito altos foram encontrados&#46; N&#237;veis elevados j&#225; foram descritos em pacientes pedi&#225;tricos cr&#237;ticos com COVID&#8208;19&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">5&#44;8&#44;12</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Outro achado consistente com disfun&#231;&#227;o card&#237;aca em pacientes do grupo MIS foi derrame pleural&#44; detectado por radiografia de t&#243;rax&#44; uma caracter&#237;stica muito menos frequente no grupo n&#227;o MIS&#46; Os outros achados radiol&#243;gicos de infiltrados intersticiais difusos bilaterais e opacidades em vidro fosco&#44; nas radiografias de t&#243;rax e na TC&#44; estavam presentes na maioria dos pacientes&#44; o que &#233; consistente com relatos anteriores&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">10&#44;18&#44;25</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Quanto ao manejo dos pacientes&#44; a maioria necessitou de algum tipo de suporte respirat&#243;rio&#59; a maioria necessitou apenas de oxigenoterapia&#44; mas cerca de 20&#37; necessitaram de VMI &#40;mediana de 7&#44;5 dias&#41;&#44; o que est&#225; dentro da faixa de uso relatada &#40;18&#8208;50&#37;&#41; descrita em outros estudos&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">5&#44;10&#44;11&#44;14</span></a> Desses&#44; 71&#37; desenvolveram SDRA&#44; principalmente grave&#44; exigiram bloqueio neuromuscular&#44; PEEP alta&#44; manobra de recrutamento alveolar e posi&#231;&#227;o prona em alguns casos&#46; Embora n&#227;o pud&#233;ssemos confirmar infec&#231;&#245;es bacterianas&#44; a antibioticoterapia foi usada em tr&#234;s quartos dos pacientes e o oseltamivir em quase metade&#44; o que pode ser explicado pelas diretrizes nacionais para o tratamento da SARS&#44; que indicam o uso inicial do oseltamivir emp&#237;rico&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">26</span></a> A hidroxicloroquina n&#227;o foi prescrita&#44; embora alguns estudos tenham relatado seu uso em 7 a 47&#37; dos pacientes&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">5&#44;10&#44;11&#44;14</span></a> Talvez essa diferen&#231;a possa ser explicada pelo fato de os casos na Europa e nos EUA terem come&#231;ado semanas ou meses antes do Brasil&#44; quando um uso mais compassivo de drogas poderia ser explicado e tamb&#233;m menos estudos estavam dispon&#237;veis&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Comparamos as caracter&#237;sticas demogr&#225;ficas e cl&#237;nicas de acordo com a presen&#231;a de comorbidades&#44; idade abaixo de um ano e necessidade de VMI&#46; Embora nossos n&#250;meros nesses subgrupos fossem pequenos&#44; encontramos diferen&#231;as significativas determinadas pela presen&#231;a de comorbidades&#46; Esses pacientes eram mais velhos e precisavam de mais suporte respirat&#243;rio&#44; com a maioria dos casos de SDRA&#46; As &#250;nicas duas mortes tamb&#233;m ocorreram nesse grupo&#46; A presen&#231;a de comorbidades aumentou de forma independente a chance de VMI&#44; mas os fatores associados a um pior progn&#243;stico precisam de mais investiga&#231;&#227;o&#46; A obesidade&#44; relatada como o pior fator progn&#243;stico em crian&#231;as com COVID&#8208;19&#44;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">5&#44;11</span></a> n&#227;o foi frequente em nossa coorte&#44; na qual as principais comorbidades significativas foram doen&#231;as neuromusculares&#44; doen&#231;as respirat&#243;rias cr&#244;nicas e c&#226;ncer&#46; Idade inferior a um ano&#44; sexo e etnia n&#227;o foram associados a casos mais graves em nosso estudo&#44; embora os lactentes tenham apresentado pior curso cl&#237;nico na China e nos EUA&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">1&#44;2</span></a> Como a MIS &#233; uma doen&#231;a pouco compreendida&#44; que parece ocorrer em uma fase subaguda da infec&#231;&#227;o por SARS&#8208;CoV&#8208;2&#44; tamb&#233;m fizemos as mesmas compara&#231;&#245;es de subgrupos e a avalia&#231;&#227;o de preditores de gravidade apenas no grupo n&#227;o MIS&#44; mas os resultados n&#227;o diferiram&#46; Como tamb&#233;m demonstrado em todos os estudos pedi&#225;tricos sobre a COVID&#8208;19&#44; a grande maioria dos nossos pacientes progrediu bem e recebeu alta&#44; com uma taxa de mortalidade de apenas 3&#37;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Nosso estudo tem algumas limita&#231;&#245;es&#46; Como incluiu apenas pacientes brasileiros&#44; isso pode limitar a generaliza&#231;&#227;o de nossos resultados&#46; Al&#233;m disso&#44; faltam alguns detalhes sobre o tratamento&#44; como o motivo do alto percentual de uso de antibi&#243;ticos ou corticosteroides&#46; Nem todos os pacientes tiveram os marcadores inflamat&#243;rios medidos&#59; portanto&#44; eles n&#227;o puderam ser comparados dependendo da gravidade da doen&#231;a&#46; Apesar dessas limita&#231;&#245;es&#44; acreditamos que nosso estudo pode contribuir para uma melhor compreens&#227;o da COVID&#8208;19&#44; pois descreve a primeira grande s&#233;rie de pacientes internados em UTIPs no hemisf&#233;rio sul&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Mostramos que as caracter&#237;sticas dessa doen&#231;a em locais tropicais e subtropicais s&#227;o semelhantes &#224;s de outros pa&#237;ses&#46; Em nossa coorte&#44; a letalidade foi baixa e as doen&#231;as cr&#244;nicas e outras comorbidades desempenharam um papel importante no desenvolvimento de formas graves da doen&#231;a&#46; Diferentemente de outros estudos&#44; a idade inferior a um ano n&#227;o foi associada a um pior progn&#243;stico&#46; Pacientes com MIS apresentaram sintomas mais graves&#44; n&#237;veis mais altos de biomarcadores inflamat&#243;rios e maior predom&#237;nio do sexo masculino&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Financiamento</span><p id="par0140" class="elsevierStylePara elsevierViewall">Conselho Nacional de Desenvolvimento Cient&#237;fico e Tecnol&#243;gico &#40;CNPq&#41;&#44; processo n&#176; 401597&#47;2020&#8208;2&#46; Funda&#231;&#227;o Carlos Chagas Filho de Amparo &#224; Pesquisa do Estado do Rio de Janeiro &#40;Faperj&#41;&#44; processo n&#176; E&#8208;26&#47;010&#46;000160&#47;2020&#44; concess&#227;o n&#176; 2020&#47;0996&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflitos de interesse</span><p id="par0145" class="elsevierStylePara elsevierViewall">Os autores declaram n&#227;o haver conflitos de interesse&#46;</p></span></span>"
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              "titulo" => "Caracter&#237;sticas demogr&#225;ficas e epidemiol&#243;gicas"
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              "titulo" => "Apresenta&#231;&#227;o cl&#237;nica"
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              "titulo" => "Confirma&#231;&#227;o do diagn&#243;stico&#44; achados laboratoriais e radiol&#243;gicos"
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              "titulo" => "Manejo e resultados cl&#237;nicos"
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    "fechaRecibido" => "2020-07-16"
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            0 => "COVID&#8208;19"
            1 => "SARS&#8208;CoV&#8208;2"
            2 => "Pediatric intensive care"
            3 => "Pediatrics"
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            0 => "COVID&#8208;19"
            1 => "SARS&#8208;CoV&#8208;2"
            2 => "Terapia intensiva pedi&#225;trica"
            3 => "Pediatria"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To describe the clinical characteristics of children and adolescents admitted to intensive care with confirmed COVID&#8208;19&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Prospective&#44; multicenter&#44; observational study&#44; in 19 pediatric intensive care units&#46; Patients aged 1 month to 19 years admitted consecutively &#40;March&#8211;May 2020&#41; were included&#46; Demographic&#44; clinical&#8208;epidemiological features&#44; treatment&#44; and outcomes were collected&#46; Subgroups were compared according to comorbidities&#44; age &#60; 1 year&#44; and need for invasive mechanical ventilation&#46; A multivariable logistic regression model was used for predictors of severity&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Seventy&#8208;nine patients were included &#40;ten with multisystemic inflammatory syndrome&#41;&#46; Median age 4 years&#59; 54&#37; male &#40;multisystemic inflammatory syndrome&#44; 80&#37;&#41;&#59; 41&#37; had comorbidities &#40;multisystemic inflammatory syndrome&#44; 20&#37;&#41;&#46; Fever &#40;76&#37;&#41;&#44; cough &#40;51&#37;&#41;&#44; and tachypnea &#40;50&#37;&#41; were common in both groups&#46; Severe symptoms&#44; gastrointestinal symptoms&#44; and higher inflammatory markers were more frequent in multisystemic inflammatory syndrome&#46; Interstitial lung infiltrates were common in both groups&#44; but pleural effusion was more prevalent in the multisystemic inflammatory syndrome group &#40;43&#37; <span class="elsevierStyleItalic">vs&#46;</span> 14&#37;&#41;&#46; Invasive mechanical ventilation was used in 18&#37; &#40;median 7&#46;5 days&#41;&#59; antibiotics&#44; oseltamivir&#44; and corticosteroids were used in 76&#37;&#44; 43&#37;&#44; and 23&#37;&#44; respectively&#44; but not hydroxychloroquine&#46; The median pediatric intensive care unit length&#8208;of&#8208;stay was five days&#59; there were two deaths &#40;3&#37;&#41; in the non&#8208; multisystemic inflammatory syndrome group&#46; Patients with comorbidities were older and comorbidities were independently associated with the need for invasive mechanical ventilation &#40;OR 5&#46;5&#59; 95&#37; CI&#44; 1&#46;43&#8211;21&#46;12&#59; p<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In Brazilian pediatric intensive care units&#44; COVID&#8208;19 had low mortality&#44; age less than 1 year was not associated with a worse prognosis&#44; and patients with multisystemic inflammatory syndrome had more severe symptoms&#44; higher inflammatory biomarkers&#44; and a greater predominance of males&#44; but only comorbidities and chronic diseases were independent predictors of severity&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Descrever as caracter&#237;sticas cl&#237;nicas de crian&#231;as e adolescentes internados em unidade de terapia intensiva com COVID&#8208;19 confirmada&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudo prospectivo&#44; multic&#234;ntrico&#44; observacional&#44; em 19 unidades de terapia intensiva pedi&#225;trica&#46; Foram inclu&#237;dos pacientes entre um m&#234;s e 19 anos&#44; admitidos consecutivamente &#40;mar&#231;o a maio de 2020&#41;&#46; As caracter&#237;sticas demogr&#225;ficas&#44; cl&#237;nico&#8208;epidemiol&#243;gicas&#44; o tratamento e os resultados foram coletados&#46; Os subgrupos foram comparados de acordo com as comorbidades&#44; idade &#60; 1 ano e necessidade de ventila&#231;&#227;o mec&#226;nica invasiva&#46; Um modelo de regress&#227;o log&#237;stica multivari&#225;vel foi utilizado para preditores de gravidade&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Setenta e nove pacientes foram inclu&#237;dos &#40;10 com s&#237;ndrome inflamat&#243;ria multi-ssist&#234;mica&#41;&#46; Mediana de idade&#44; quatro anos&#59; 54&#37; eram do sexo masculino &#40;s&#237;ndrome inflamat&#243;ria multissist&#234;mica&#44; 80&#37;&#41;&#59; 41&#37; tinham comorbidades &#40;s&#237;ndrome inflamat&#243;ria multissist&#234;mica&#44; 20&#37;&#41;&#46; Febre &#40;76&#37;&#41;&#44; tosse &#40;51&#37;&#41; e taquipneia &#40;50&#37;&#41; foram comuns nos dois grupos&#46; Sintomas graves egastrointestinais e marcadores inflamat&#243;rios mais elevados foram mais frequentes na presen&#231;a de s&#237;ndrome inflamat&#243;ria multissist&#234;mica&#46; Infiltrados intersticiais pulmonares foram comuns em ambos os grupos&#44; mas o derrame pleural foi mais prevalente no grupo com s&#237;ndrome inflamat&#243;ria multissist&#234;mica &#40;43&#37; vs&#46; 14&#37;&#41;&#46; A ventilac&#184;&#227;o mec&#226;nica invasiva foi utilizada em 18&#37; &#40;mediana 7&#44;5 dias&#41;&#59; antibi&#243;ticos&#44; oseltamivir e corticosteroides foram utilizados em 76&#37;&#44; 43&#37; e 23&#37;&#44; respectivamente&#44; mas n&#227;o a hidroxicloroquina&#46; A mediana do tempo de perman&#234;ncia na unidade de terapia intensiva pedi&#225;trica foi de 5 dias&#59; duas mortes ocorreram &#40;3&#37;&#41; no grupo n&#227;o- s&#237;ndrome inflamat&#243;ria multissist&#234;mica&#46; Os pacientes com comorbidades eram mais velhos&#44; e as comorbidades foram independentemente associadas &#224; necessidade de ventilac&#184;&#227;o mec&#226;nica invasiva&#40;<span class="elsevierStyleItalic">OR</span> 5&#44;5&#59; IC95&#37;&#44; 1&#44;43-21&#44;12&#59; P 0&#44;01&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#245;es</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Nas unidades de terapia intensiva pedi&#225;trica brasileiras&#44; a COVID&#8208;19 apresentou baixa mortalidade&#44; a idade inferior a um ano n&#227;o foi associada a um pior progn&#243;stico&#44; os pacientes com s&#237;ndrome inflamat&#243;ria multissist&#234;mica apresentaram sintomas mais graves&#44; biomarcadores inflamat&#243;rios mais elevados e uma grande predomin&#226;ncia no sexo masculino&#44; mas apenas a presen&#231;a de comorbidades e doen&#231;as cr&#244;nicas foi um preditor independente de gravidade&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0050">Como citar este artigo&#58; Prata&#8208;Barbosa A&#44; Lima&#8208;Setta F&#44; Santos GR&#44; Lanziotti VS&#44; Castro RE&#44; Souza DC&#44; et al&#46; Pediatric patients with COVID&#8208;19 admitted to intensive care units in Brazil&#58; a prospective multicenter study&#46; J Pediatr &#40;Rio J&#41;&#46; 2020&#59;96&#58;570&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0055">Estudo vinculado &#224; Rede Brasileira de Pesquisa em Medicina Intensiva Pedi&#225;trica &#40;BRnet&#8208;PIC&#41;&#44; Brasil&#46;</p>"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">COVID&#8208;19&#44; doen&#231;a do coronav&#237;rus 2019&#59; IIQ&#44; intervalo interquartil&#59; MIS&#44; S&#237;ndrome Inflamat&#243;ria Multissist&#234;mica&#59; UTIP&#44; Unidade de Terapia Intensiva Pedi&#225;trica&#44; SpO<span class="elsevierStyleInf">2</span>&#44; satura&#231;&#227;o de oxig&#234;nio no ox&#237;metro de pulso&#46;</p>"
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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">5&#44;2 &#40;1&#44;5&#8208;8&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;1&#8208;10&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Lactentes &#40;&#60; 12 m&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">17 &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">19 &#40;24&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Crian&#231;a pequena &#40;&#8805; 12 m&#44; &#60; 3 a&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">16 &#40;23&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">18 &#40;23&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pr&#233;&#8208;escolar &#40;&#8805; 3 a&#44; &#60; 5 a&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Crian&#231;a no Ensino Fundamental I &#40;&#8805; 5 a&#44; &#60; 12 a&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">15 &#40;22&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;40&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">19 &#40;24&#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
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Adolescente &#40;&#8805; 12 a&#44; &#60; 18 a&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">13 &#40;19&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14 &#40;18&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Jovem Adulto &#40;&#8805; 18 a&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Sexo</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Masculino&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">35 &#40;51&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8 &#40;80&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">43 &#40;54&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Feminino&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">34 &#40;49&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">36 &#40;46&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Cor da pele&#47;etnia</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Branca&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">40 &#40;58&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6 &#40;60&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">46 &#40;58&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Parda&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">19 &#40;28&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">20 &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Negra&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">10 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;20&#41;&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">12 &#40;15&#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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Asi&#225;tico&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">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Comorbidades</span>&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">30 &#40;43&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">32 &#40;41&#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
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Doen&#231;a neuromuscular<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&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="left" valign="\n
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                  \t\t\t\t">9 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">10 &#40;31&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&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"><span class="elsevierStyleHsp" style=""></span>Doen&#231;a respirat&#243;ria cr&#244;nica<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;20&#41;&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">&#8208;&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">6 &#40;19&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&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"><span class="elsevierStyleHsp" style=""></span>Doen&#231;a onco&#8208;hematol&#243;gica&nbsp;\t\t\t\t\t\t\n
                  \t\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">6 &#40;20&#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">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\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">6 &#40;19&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&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"><span class="elsevierStyleHsp" style=""></span>Doen&#231;a card&#237;aca cong&#234;nita&nbsp;\t\t\t\t\t\t\n
                  \t\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">4 &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;50&#41;&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">5 &#40;16&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&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 ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Subnutri&#231;&#227;o&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="left" valign="\n
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                  \t\t\t\t">4 &#40;13&#41;&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="left" valign="\n
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                  \t\t\t\t">&#8208;&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="left" valign="\n
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                  \t\t\t\t">4 &#40;13&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&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"><span class="elsevierStyleHsp" style=""></span>Diabetes&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="left" valign="\n
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                  \t\t\t\t">2 &#40;7&#41;&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\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">2 &#40;6&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&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"><span class="elsevierStyleHsp" style=""></span>Prematuridade&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;7&#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">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\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">2 &#40;6&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&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"><span class="elsevierStyleHsp" style=""></span>Doen&#231;a hep&#225;tica cr&#244;nica&nbsp;\t\t\t\t\t\t\n
                  \t\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">1 &#40;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">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\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">1 &#40;3&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&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"><span class="elsevierStyleHsp" style=""></span>Obesidade&nbsp;\t\t\t\t\t\t\n
                  \t\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">1 &#40;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">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\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">1 &#40;3&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&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"><span class="elsevierStyleItalic">Contato comum caso suspeito &#40;N</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">o</span></span><span class="elsevierStyleItalic">&#46; 31&#41;</span>&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="left" valign="\n
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                  \t\t\t\t">24 &#40;35&#41;&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><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">31 &#40;39&#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"><span class="elsevierStyleHsp" style=""></span>Em casa&nbsp;\t\t\t\t\t\t\n
                  \t\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">20 &#40;83&#41;&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="left" valign="\n
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                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\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">27 &#40;87&#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"><span class="elsevierStyleHsp" style=""></span>Outro lugar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#40;17&#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">3&nbsp;\t\t\t\t\t\t\n
                  \t\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">4 &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Principal s&#237;ndrome cl&#237;nica na apresenta&#231;&#227;o</span></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"><span class="elsevierStyleHsp" style=""></span>Respirat&#243;ria<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47 &#40;68&#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="" valign="\n
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                  \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">47 &#40;60&#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"><span class="elsevierStyleHsp" style=""></span>MIS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#40;100&#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">10 &#40;13&#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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Condi&#231;&#227;o similar &#224; doen&#231;a de Kawasaki&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#40;60&#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">6 &#40;60&#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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Disfun&#231;&#227;o card&#237;aca aguda&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#40;20&#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">2 &#40;20&#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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>S&#237;ndrome do choque t&#243;xico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\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">1 &#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
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                  \t\t\t\t">1 &#40;10&#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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>S&#237;ndrome de ativa&#231;&#227;o de macr&#243;fagos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\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">1 &#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
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                  \t\t\t\t">1 &#40;10&#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
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                  \t\t\t\t">&#8208;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Sintomas antes da hospitaliza&#231;&#227;o&#44; mediana &#40;IIQ&#41;&#44; dias</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Caracter&#237;sticas cl&#237;nicas na apresenta&#231;&#227;o</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Febre&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tosse&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Taquipneia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Baixa SpO<span class="elsevierStyleInf">2</span> &#40;&#60;92&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Prostra&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Retra&#231;&#227;o tor&#225;cica&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Coriza&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diarreia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Recusa em alimentar&#8208;se&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>V&#244;mitos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">16 &#40;21&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Desidrata&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Batimento de asa nasal&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Gem&#234;ncia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cianose&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5 &#40;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hipotens&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Teste r&#225;pido para v&#237;rus sincicial respirat&#243;rio&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Outro v&#237;rus&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rinov&#237;rus humano&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ValoresMediana &#40;IIQ&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ValoresMediana &#40;IIQ&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">N<span class="elsevierStyleSup">o</span>&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ValoresMediana &#40;IIQ&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Contagem total de leuc&#243;citos &#40;x1&#46;000&#47;&#956;L&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">18&#46;275 &#40;14&#46;293&#8208; 23&#46;868&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12&#46;520 &#40;8&#46;382&#8208;19&#46;100&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Contagem deplaquetas&#40;x1&#44;000&#47;&#956;L&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">260&#46;500 &#40;159&#46;250&#8208;374&#46;500&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">226&#46;500 &#40;136&#46;750&#8208;367&#46;000&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Linfopenia N</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">o</span></span><span class="elsevierStyleItalic">&#46; &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">26 &#40;38&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Prote&#237;na C&#8208;reativa &#40;mg&#47;dL&#41;&#44;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;0&#46;6&#8208;18&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">10 &#40;9&#8208;30&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5&#46;1 &#40;0&#46;7&#8208;20&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Velocidade de hemossedimenta&#231;&#227;o &#40;mm&#47;1</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">a</span></span><span class="elsevierStyleItalic">h&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Achados radiol&#243;gicos na admiss&#227;o na UTIP</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Imagens alteradas&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Imagens alteradas&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Radiografias tor&#225;cicas anormais</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Infiltrado intersticial difuso&#44; bilateral&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Infiltrado intersticial&#44; localizado&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Consolida&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Atelectasia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>PEEP mais alta&#44; mediana &#40;IIQ&#41;&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\ttop\n
                  \t\t\t\t">9&#44;0 &#40;7&#44;0&#44; 11&#44;0&#41;&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\ttop\n
                  \t\t\t\t">12&#44;0 &#40;12&#44;0&#44; 12&#44;0&#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">9&#44;5 &#40;7&#44;0&#44; 12&#44;0&#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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Posi&#231;&#227;o prona intermitente&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Recrutamento alveolar&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">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6 &#40;60&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Hipertens&#227;o arterial pulmonar</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0 &#40;0&#41;&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  " align="left" valign="\n
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                  \t\t\t\t">71 &#40;90&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Morte&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;10&#41;&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" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Caracter&#237;stica&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  " colspan="3" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Comorbidades</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Idade inferior a um ano</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Ventila&#231;&#227;o mec&#226;nica invasiva</th></tr><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">Sim&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">N&#227;o&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">p&#8208;valor&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">Sim&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">N&#227;o&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">p&#8208;valor&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">Sim&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">N&#227;o&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">p&#8208;valor&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"><span class="elsevierStyleItalic">Idade&#44; mediana &#40;IIQ&#41;&#44; a</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">7&#44;5 &#40;2&#44;1&#44; 12&#44;4&#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">1&#44;8 &#40;0&#44;8&#44; 7&#44;0&#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">0&#44;01<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">c</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">0&#44;5 &#40;0&#44;2&#44; 0&#44;7&#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">7&#44;0 &#40;1&#44;9&#44; 12&#44;4&#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="" 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">5&#44;6 &#40;1&#44;2&#44; 10&#44;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">4&#44;2 &#40;1&#44;2&#44; 10&#44;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">0&#44;94<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sexo&#44; N</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">o</span></span><span class="elsevierStyleItalic">&#46; &#40;&#37;&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>Masculino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#40;53&#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">26 &#40;55&#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">1<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</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">9 &#40;47&#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">34 &#40;57&#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">0&#44;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#40;43&#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">37 &#40;57&#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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;51<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a></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"><span class="elsevierStyleHsp" style=""></span>Feminino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;47&#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">21 &#40;45&#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="" 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">10 &#40;53&#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">26 &#40;43&#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="" 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">8 &#40;57&#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">28 &#40;43&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Etnia&#44; No&#46; &#40;&#37;&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>Branca&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#40;53&#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">29 &#40;62&#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">0&#44;57<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</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 &#40;42&#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">38 &#40;63&#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">0&#44;17<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</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 &#40;57&#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">38 &#40;58&#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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a></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"><span class="elsevierStyleHsp" style=""></span>N&#227;o branca&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;47&#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">18 &#40;38&#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="" 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">11 &#40;58&#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">22 &#40;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="" 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">6 &#40;43&#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">27 &#40;42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Comorbidades&#44; N</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">o</span></span><span class="elsevierStyleItalic">&#46; &#40;&#37;&#41;</span></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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Sim&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="left" valign="\n
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                  \t\t\t\t">&#8208;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8208;&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">&#8208;&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">5 &#40;26&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">27 &#40;45&#41;&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">0&#44;19<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">10 &#40;71&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">22 &#40;34&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " rowspan="2" align="left" valign="\n
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                  \t\t\t\t">0&#44;01<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a></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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>N&#227;o&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="left" valign="\n
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                  \t\t\t\t">&#8208;&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">&#8208;&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">&#8208;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14 &#40;74&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">33 &#40;55&#41;&nbsp;\t\t\t\t\t\t\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><td class="td" title="\n
                  \t\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 &#40;29&#41;&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">43 &#40;66&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Principal apresenta&#231;&#227;o&#44; N</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">o</span></span><span class="elsevierStyleItalic">&#46; &#40;&#37;&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>Respirat&#243;ria&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">22 &#40;69&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">25 &#40;53&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;11<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">13 &#40;68&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">34 &#40;57&#41;&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">0&#44;72<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11 &#40;79&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">26 &#40;48&#41;&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">0&#44;08<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a>&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 ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>MIS&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">2 &#40;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8 &#40;17&#41;&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">0&#44;18<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;11&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8 &#40;13&#41;&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">1<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9 &#40;17&#41;&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">0&#44;67<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a>&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 ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Condi&#231;&#227;o similar &#224; doen&#231;a de Kawasaki&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;50&#41;&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">0&#44;56<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</span></a>&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">2 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;56<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</span></a>&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">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6 &#40;67&#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">0&#44;30<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</span></a>&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Disfun&#231;&#227;o card&#237;aca aguda&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">2 &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&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">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;22&#41;&nbsp;\t\t\t\t\t\t\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
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>S&#237;ndrome do choque t&#243;xico&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">1 &#40;13&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;12&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>S&#237;ndrome da ativa&#231;&#227;o de macr&#243;fagos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;11&#41;&nbsp;\t\t\t\t\t\t\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
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Outras&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">8 &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;85<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;22&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">18 &#40;30&#41;&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">0&#44;73<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;14&#41;&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">20 &#40;37&#41;&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">0&#44;12<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="10" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Manejo&#44; N</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">o</span></span><span class="elsevierStyleItalic">&#46; &#40;&#37;&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>Apenas oxigenoterapia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">18 &#40;56&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14 &#40;31&#41;&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">0&#44;05<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5 &#40;26&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">27 &#40;45&#41;&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">0&#44;24<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8208;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">32 &#40;49&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Ventila&#231;&#227;o n&#227;o invasiva&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;39<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5 &#40;8&#41;&nbsp;\t\t\t\t\t\t\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
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Ventila&#231;&#227;o mec&#226;nica invasiva&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">10 &#40;31&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;01<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;16&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11 &#40;18&#41;&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">1<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</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">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8208;&nbsp;\t\t\t\t\t\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
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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
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Dias de uso&#44; mediana &#40;IIQ&#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">7&#44;5 &#40;5&#44;5&#8208; 9&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12&#44;5 &#40;8&#44;8&#44; 16&#44;2&#41;&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\ttop\n
                  \t\t\t\t">0&#44;67<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">c</span></a>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#44;0 &#40;9&#44;0&#8208; 9&#44;0&#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">7&#44;0 &#40;5&#44;0&#44; 11&#44;0&#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">0&#44;66<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">c</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">7&#44;5 &#40;5&#44;0&#8208; 10&#44;0&#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">&#8208;&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
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Diagn&#243;stico de SDRA&#44; N</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">o</span></span><span class="elsevierStyleItalic">&#46; &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8 &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;4&#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">0&#44;01<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</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">1 &#40;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">9 &#40;15&#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">0&#44;44<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</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">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8208;&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"><span class="elsevierStyleItalic">TP UTIP&#44; dias&#44; mediana &#40;IIQ&#41;</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">5&#44;5 &#40;2&#44;8&#44; 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">5 &#40;2&#8208;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">0&#44;88<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">c</span></a>&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">6 &#40;4&#8208;11&#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">5 &#40;2&#8208;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">0&#44;18<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">c</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">12 &#40;6&#8208;18&#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">5&#44;0 &#40;2&#8208;7&#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">0&#44;01<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Desfecho&#44; N</span><span class="elsevierStyleSup">o</span><span class="elsevierStyleItalic">&#46; &#40;&#37;&#41;</span></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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Alta hospitalar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26 &#40;81&#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">45 &#40;96&#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">0&#44;10<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</span></a>&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">17 &#40;89&#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">54 &#40;90&#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">0&#44;79<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</span></a>&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">10 &#40;71&#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">61 &#40;94&#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">0&#44;01<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</span></a>&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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Morte&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">2 &#40;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">0 &#40;0&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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">0 &#40;0&#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">2 &#40;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="" 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">2 &#40;14&#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">0 &#40;0&#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="" 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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Transfer&#234;ncia para outro hospital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#40;12&#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">2 &#40;4&#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="" 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">2 &#40;11&#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">4 &#40;7&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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">2 14&#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">4 &#40;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="" 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></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
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            1 => array:2 [
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                0 => """
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tabela 4 b &#8208; <span class="elsevierStyleItalic">Odds ratio</span> n&#227;o ajustados e ajustados<a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">d</span></a> e intervalos de confian&#231;a de 95&#37; para pacientes pedi&#225;tricos com COVID&#8208;19&#44; de acordo com a necessidade de ventila&#231;&#227;o mec&#226;nica invasiva &#40;n &#61; 79&#41;</th></tr><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">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Ventila&#231;&#227;o mec&#226;nica invasiva</th></tr><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">N&#227;o ajustadoOR &#40;CI 95&#37;&#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">p&#8208;valor&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">AjustadoOR &#40;CI 95&#37;&#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">p&#8208;valor&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">Idade &#60; 1 ano&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&#44;00 &#40;0&#44;99&#8208;1&#44;01&#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">0&#44;69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;99 &#40;0&#44;99&#8208;1&#44;00&#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">0&#44;64&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">Sexo&#44; masculino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;57 &#40;0&#44;18&#8208;1&#44;82&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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Vol. 96. Núm. 5.
Páginas 582-592 (setembro - outubro 2020)
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Vol. 96. Núm. 5.
Páginas 582-592 (setembro - outubro 2020)
Artigo Original
Open Access
Pediatric patients with COVID‐19 admitted to intensive care units in Brazil: a prospective multicenter study
Pacientes pediátricos com COVID‐19 admitidos em Unidades de Terapia Intensiva no Brasil: um estudo prospectivo multicêntrico
Visitas
7478
Arnaldo Prata‐Barbosaa,
Autor para correspondência
arnaldo.prata@idor.org

Autor para correspondência.
, Fernanda Lima‐Settaa, Gustavo Rodrigues dos Santosa, Vanessa Soares Lanziottib, Roberta Esteves Vieira de Castroc, Daniela Carla de Souzad, Carlos Eduardo Raymundoa, Felipe Rezende Caino de Oliveirae, Lucio Flavio Peixoto de Limaf, Cristian Tedesco Tonialg, José Colleti Jr.h, Ana Paula Novaes Bellinati, Vivian Botelho Lorenzoj, Raquel de Seixas Zeitelk, Lucas Pulcheril, Fernanda Ciuffo Monte da Costam, Fabíola Peixoto Ferreira La Torren, Elaine Augusta das Neves Figueiredoo, Thiago Peres da Silvap, Paula Marins Riveiroq..., Isabele Coelho Fonseca da Motar, Igor Bromonschenkel Brandãos, Zina Maria Almeida de Azevedot, Simone Camera Gregoryu, Fernanda Raquel Oliveira Boedov, Rosana Novais de Carvalhow, Natália Almeida de Arnaldo Silva Rodriguez Castrox, Daniel Hilário Santos Genuy, Flavia Andrea Krepel Forondad, Antonio José Ledo A. Cunhab, Maria Clara de Magalhães‐Barbosaa, Rede Brasileira de Pesquisa em Medicina Intensiva Pediátrica (BRnet‐PIC) zVer más
a Instituto D’Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, RJ, Brasil
b Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
c Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
d Hospital Sírio Libanês, São Paulo, SP, Brasil
e Hospital Alvorada Moema, São Paulo, SP, Brasil
f Hospital Sepaco, São Paulo, SP, Brasil
g Pontifícia Universidade Católica (PUC‐RS), Porto Alegre, RS, Brasil
h Hospital Assunção, São Bernardo do Campo, SP, Brasil
i Hospital Martagão Gesteira, Salvador, BA, Brasil
j Hospital Couto Maia, Salvador, BA, Brasil
k Universidade do Estado do Rio de Janeiro (UERJ), Hospital Pedro Ernesto, Rio de Janeiro, RJ, Brasil
l Hospital Rios D’Or, Rio de Janeiro, RJ, Brasil
m Hospital Quinta D’Or, Rio de Janeiro, RJ, Brasil
n Hospital Sino Brasileiro, Osasco, SP, Brasil
o Hospital Pediátrico Unimed, Belém, PA, Brasil
p Hospital Real D’Or, Rio de Janeiro, RJ, Brasil
q Hospital Caxias D’Or, Duque de Caxias, RJ, Brasil
r Hospital Jutta Batista, Rio de Janeiro, RJ, Brasil
s Hospital Niteroi D’Or, Rio de Janeiro, RJ, Brasil
t Instituto Fernandes Figueira, Fiocruz, Rio de Janeiro, RJ, Brasil
u Hospital Estadual da Criança, Rio de Janeiro, RJ, Brasil
v Hospital Norte D’Or, Rio de Janeiro, RJ, Brasil
w Hospital Santa Izabel, Santa Casa da Misericórdia, Salvador, BA, Brasil
x Hospital da Criança, Faculdade de Medicina, São José do Rio Preto, SP, Brasil
y Hospital Estadual Getúlio Vargas, Rio de Janeiro, RJ, Brasil
z Rede Brasileira de Pesquisa em Medicina Intensiva Pediátrica (BRnet‐PIC), Brasil
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Tabelas (4)
Tabela 1. Dados demográficos, epidemiológicos e clínicos de pacientes pediátricos com COVID‐19
Tabela 2. Confirmação diagnóstica, achados laboratoriais e radiológicos de pacientes pediátricos com COVID‐19
Tabela 3. Manejo e resultados clínicos de pacientes pediátricos com COVID‐19
Tabela 4a. Dados demográficos e características clínicas de pacientes pediátricos com COVID‐19 de acordo com a presença de comorbidades, idade inferior a um ano e necessidade de ventilação mecânica invasiva em todos os pacientes (n = 79).
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Abstract
Objective

To describe the clinical characteristics of children and adolescents admitted to intensive care with confirmed COVID‐19.

Method

Prospective, multicenter, observational study, in 19 pediatric intensive care units. Patients aged 1 month to 19 years admitted consecutively (March–May 2020) were included. Demographic, clinical‐epidemiological features, treatment, and outcomes were collected. Subgroups were compared according to comorbidities, age < 1 year, and need for invasive mechanical ventilation. A multivariable logistic regression model was used for predictors of severity.

Results

Seventy‐nine patients were included (ten with multisystemic inflammatory syndrome). Median age 4 years; 54% male (multisystemic inflammatory syndrome, 80%); 41% had comorbidities (multisystemic inflammatory syndrome, 20%). Fever (76%), cough (51%), and tachypnea (50%) were common in both groups. Severe symptoms, gastrointestinal symptoms, and higher inflammatory markers were more frequent in multisystemic inflammatory syndrome. Interstitial lung infiltrates were common in both groups, but pleural effusion was more prevalent in the multisystemic inflammatory syndrome group (43% vs. 14%). Invasive mechanical ventilation was used in 18% (median 7.5 days); antibiotics, oseltamivir, and corticosteroids were used in 76%, 43%, and 23%, respectively, but not hydroxychloroquine. The median pediatric intensive care unit length‐of‐stay was five days; there were two deaths (3%) in the non‐ multisystemic inflammatory syndrome group. Patients with comorbidities were older and comorbidities were independently associated with the need for invasive mechanical ventilation (OR 5.5; 95% CI, 1.43–21.12; p=0.01).

Conclusions

In Brazilian pediatric intensive care units, COVID‐19 had low mortality, age less than 1 year was not associated with a worse prognosis, and patients with multisystemic inflammatory syndrome had more severe symptoms, higher inflammatory biomarkers, and a greater predominance of males, but only comorbidities and chronic diseases were independent predictors of severity.

Keywords:
COVID‐19
SARS‐CoV‐2
Pediatric intensive care
Pediatrics
Brazil
Resumo
Objetivo

Descrever as características clínicas de crianças e adolescentes internados em unidade de terapia intensiva com COVID‐19 confirmada.

Método

Estudo prospectivo, multicêntrico, observacional, em 19 unidades de terapia intensiva pediátrica. Foram incluídos pacientes entre um mês e 19 anos, admitidos consecutivamente (março a maio de 2020). As características demográficas, clínico‐epidemiológicas, o tratamento e os resultados foram coletados. Os subgrupos foram comparados de acordo com as comorbidades, idade < 1 ano e necessidade de ventilação mecânica invasiva. Um modelo de regressão logística multivariável foi utilizado para preditores de gravidade.

Resultados

Setenta e nove pacientes foram incluídos (10 com síndrome inflamatória multi-ssistêmica). Mediana de idade, quatro anos; 54% eram do sexo masculino (síndrome inflamatória multissistêmica, 80%); 41% tinham comorbidades (síndrome inflamatória multissistêmica, 20%). Febre (76%), tosse (51%) e taquipneia (50%) foram comuns nos dois grupos. Sintomas graves egastrointestinais e marcadores inflamatórios mais elevados foram mais frequentes na presença de síndrome inflamatória multissistêmica. Infiltrados intersticiais pulmonares foram comuns em ambos os grupos, mas o derrame pleural foi mais prevalente no grupo com síndrome inflamatória multissistêmica (43% vs. 14%). A ventilac¸ão mecânica invasiva foi utilizada em 18% (mediana 7,5 dias); antibióticos, oseltamivir e corticosteroides foram utilizados em 76%, 43% e 23%, respectivamente, mas não a hidroxicloroquina. A mediana do tempo de permanência na unidade de terapia intensiva pediátrica foi de 5 dias; duas mortes ocorreram (3%) no grupo não- síndrome inflamatória multissistêmica. Os pacientes com comorbidades eram mais velhos, e as comorbidades foram independentemente associadas à necessidade de ventilac¸ão mecânica invasiva(OR 5,5; IC95%, 1,43-21,12; P 0,01).

Conclusões

Nas unidades de terapia intensiva pediátrica brasileiras, a COVID‐19 apresentou baixa mortalidade, a idade inferior a um ano não foi associada a um pior prognóstico, os pacientes com síndrome inflamatória multissistêmica apresentaram sintomas mais graves, biomarcadores inflamatórios mais elevados e uma grande predominância no sexo masculino, mas apenas a presença de comorbidades e doenças crônicas foi um preditor independente de gravidade.

Palavras‐chave:
COVID‐19
SARS‐CoV‐2
Terapia intensiva pediátrica
Pediatria
Brasil
Texto Completo
Introdução

O Brasil se tornou o epicentro da infecção pelo novo coronavírus (SARS‐CoV‐2) na América do Sul e o segundo país com o maior número de casos e mortes no mundo. A COVID‐19, como essa doença foi chamada pela Organização Mundial da Saúde, ainda representa um desafio na população pediátrica, embora o número e a gravidade dos casos sejam menores quando comparados à população adulta. Dados de vários países mostram que crianças e adolescentes foram responsáveis por menos de 2% dos casos sintomáticos, com taxas de hospitalização (0,6‐20%) e mortalidade (0‐4%) significativamente menores do que nos adultos.1–5 Bebês e crianças com doenças crônicas prévias representam a população pediátrica mais vulnerável, com maior gravidade.1,2,4,5 Recentemente, vários países relataram casos de uma síndrome inflamatória multissistêmica (MIC, do inglês multisystemic inflammatory syndrome) em crianças (MIS‐C) temporariamente associada à COVID‐19. Essa síndrome é caracterizada por febre prolongada, sintomas gastrointestinais e marcadores inflamatórios alterados, associados a sinais de disfunção orgânica, insuficiência cardíaca aguda, doença de Kawasaki (completa ou não) ou síndrome do choque tóxico.6–8

O relato da experiência latino‐americana com a COVID‐19 em pediatria ainda é bastante limitado, principalmente em relação a crianças internadas em unidades de terapia intensiva. Este estudo tem como objetivo descrever as características clínicas de uma coorte de crianças e adolescentes internados em Unidades de Terapia Intensiva Pediátricas (UTIPs) no Brasil.

Material e métodosDesenho do estudo, seleção de pacientes e local do estudo

Este é um estudo prospectivo, multicêntrico, feito em 19 UTIPs associadas à Rede Brasileira de Pesquisa em Terapia Intensiva Pediátrica (Brazilian Research Network in Pediatric Intensive Care, BRnet‐PIC). Pacientes pediátricos (um mês a 19 anos) com COVID‐19 confirmada foram incluídos consecutivamente entre 1° de março e 31 de maio de 2020, após a obtenção do consentimento informado. O estudo foi aprovado pelos Comitês de Ética em pesquisa de todas as instituições.

Diagnóstico e coleta de dados

O diagnóstico de COVID‐19 foi confirmado pelo ensaio de reação em cadeia da polimerase com transcrição reversa (RT‐PCR) a partir de swabs oro/nasofaríngeos ou aspirados traqueais e quando fora do período de positividade para RT‐PCR, foram usados anticorpos IgM e/ou IgG positivos contra SARS‐CoV‐2. Os dados demográficos, epidemiológicos, clínicos e de desfecho dos pacientes foram coletados prospectivamente, em formulários padronizados de relato de caso (REDCap, Vanderbilt University, EUA). Os pacientes com MIS e não MIS foram comparados, de acordo com a presença de comorbidades, idade inferior a um ano e necessidade de ventilação mecânica invasiva (VMI).

Processamento de dados e análise estatística

As variáveis categóricas foram descritas como frequências e porcentagens e as variáveis contínuas como medianas e intervalos interquartis (IIQs). As comparações entre os grupos foram feitas pelo teste do qui‐quadrado ou exato de Fisher para variáveis categóricas e teste de Mann‐Whitney para variáveis contínuas. Um modelo de regressão logística multivariável foi usado para avaliar a associação das covariáveis com idade inferior a um ano, sexo, etnia e presença de comorbidades com as formas mais graves da doença, caracterizadas pela necessidade de VMI. Foram estabelecidos um nível de significância de 5% (bicaudal) e intervalos de confiança de 95%. O software R, versão 3.6.1 (R Foundation, Viena, Áustria), foi usado para a análise estatística.

ResultadosCaracterísticas demográficas e epidemiológicas

Foram incluídos 79 pacientes (10 com MIS). No geral, a média de idade foi de quatro anos, 54% eram do sexo masculino (MIS, 80%), 58% brancos e 41% tinham comorbidades prévias (MIS, 20%), nas quais predominaram doenças neuromusculares (28%), principalmente encefalopatia não progressiva. Outras comorbidades, como doença respiratória crônica, doença onco‐hematológica, doença cardíaca congênita e desnutrição, também foram prevalentes, representaram juntas 27% do total. Trinta e um pacientes (39%) relataram contato com um caso suspeito (domicílio, 87%) (tabela 1).

Tabela 1.

Dados demográficos, epidemiológicos e clínicos de pacientes pediátricos com COVID‐19

Característica  Não MIS, No. (%)  MIS,No. (%)  Total,No. (%) 
Total  69 (100)  10 (100)  79 (100) 
Idade, mediana (IIQ), y  4 (1‐10,5)  5,2 (1,5‐8,4)  4 (1‐10,3) 
Lactentes (< 12 m)  17 (25)  2 (20)  19 (24) 
Criança pequena (≥ 12 m, < 3 a)  16 (23)  2 (20)  18 (23) 
Pré‐escolar (≥ 3 a, < 5 a)  6 (9)  1 (10)  7 (9) 
Criança no Ensino Fundamental I (≥ 5 a, < 12 a)  15 (22)  4 (40)  19 (24) 
Adolescente (≥ 12 a, < 18 a)  13 (19)  1 (10)  14 (18) 
Jovem Adulto (≥ 18 a)  2 (3)  0 (0)  2 (3) 
Sexo
Masculino  35 (51)  8 (80)  43 (54) 
Feminino  34 (49)  2 (20)  36 (46) 
Cor da pele/etnia
Branca  40 (58)  6 (60)  46 (58) 
Parda  19 (28)  1 (10)  20 (25) 
Negra  10 (14)  2 (20)  12 (15) 
Asiático  0 (0)  1 (10)  1 (1) 
Comorbidades  30 (43)  2 (20)  32 (41) 
Doença neuromusculara  9 (30)  1 (50)  10 (31)c 
Doença respiratória crônicab  6 (20)  ‐  6 (19)c 
Doença onco‐hematológica  6 (20)  ‐  6 (19)c 
Doença cardíaca congênita  4 (13)  1 (50)  5 (16)c 
Subnutrição  4 (13)  ‐  4 (13)c 
Diabetes  2 (7)  ‐  2 (6)c 
Prematuridade  2 (7)  ‐  2 (6)c 
Doença hepática crônica  1 (3)  ‐  1 (3)c 
Obesidade  1 (3)  ‐  1 (3)c 
Contato comum caso suspeito (No. 31)  24 (35)    31 (39) 
Em casa  20 (83)  27 (87) 
Outro lugar  4 (17)  4 (13) 
Principal síndrome clínica na apresentação
Respiratóriad  47 (68)    47 (60) 
MIS  ‐  10 (100)  10 (13) 
Condição similar à doença de Kawasaki  ‐  6 (60)  6 (60) 
Disfunção cardíaca aguda  ‐  2 (20)  2 (20) 
Síndrome do choque tóxico  ‐  1 (10)  1 (10) 
Síndrome de ativação de macrófagos  ‐  1 (10)  1 (10) 
Outrae  22 (32)  ‐  22 (28) 
Sintomas antes da hospitalização, mediana (IIQ), dias  5 (2‐8)  2 (1‐3)  4 (2‐8) 
Características clínicas na apresentação
Febre  51 (75)  8 (80)  59 (76) 
Tosse  36 (53)  4 (40)  40 (51) 
Taquipneia  33 (49)  6 (60)  39 (50) 
Baixa SpO2 (<92%)  19 (28)  4 (40)  23 (29) 
Prostração  13 (19)  6 (60)  19 (24) 
Retração torácica  17 (25)  1 (10)  18 (23) 
Coriza  16 (24)  1 (10)  17 (22) 
Diarreia  12 (18)  4 (40)  16 (21) 
Recusa em alimentar‐se  11 (16)  5 (50)  16 (21) 
Vômitos  10 (15)  6 (60)  16 (21) 
Desidratação  9 (13)  4 (40)  13 (17) 
Batimento de asa nasal  6 (9)  2 (20)  8 (10) 
Gemência  4 (6)  3 (30)  7 (9) 
Cianose  4 (6)  1 (10)  5 (6) 
Hipotensão  3 (4)  2 (20)  5 (6) 
Garganta avermelhada  2 (3)  1 (10)  3 (4) 

COVID‐19, doença do coronavírus 2019; IIQ, intervalo interquartil; MIS, Síndrome Inflamatória Multissistêmica; UTIP, Unidade de Terapia Intensiva Pediátrica, SpO2, saturação de oxigênio no oxímetro de pulso.

a

Encefalopatia não progressiva (n = 7), outras causas (n = 2).

b

Asma (n = 3), displasia broncopulmonar (n = 1), traqueomalácia (n = 1), outros (n = 3)d.

c

Alguns pacientes apresentaram mais de uma comorbidade.

d

Pneumonia, 23; bronquiolite, 10; outros, 14.

e

Gastrointestinal, 8; neurológico, 4; diversos, 10.

Apresentação clínica

Na hospitalização, 47 pacientes (60%) apresentavam sintomas respiratórios, a maioria pneumonia ou bronquiolite (70%), 10 (13%) apresentavam MIS e 60% apresentavam uma condição semelhante à doença de Kawasaki. Os outros 22 (28%) apresentavam principalmente sintomas gastrointestinais e neurológicos (tabela 1). A mediana do tempo dos sintomas antes da hospitalização foi de cinco dias no grupo não MIS e dois dias no grupo MIS. Os sinais e sintomas mais comuns na apresentação foram febre (76%), tosse (51%) e taquipneia (50%). Entretanto, outros achados também foram prevalentes (tabela 1). No grupo MIS, sintomas graves como taquipneia (60%), baixa SpO2 (40%), prostração (60%), gemência (30%), hipotensão (20%), batimento de asa nasal (20%) e cianose (10%), bem como sintomas gastrointestinais (40‐60%), foram mais frequentes do que no grupo não MIS (tabela 1).

Confirmação do diagnóstico, achados laboratoriais e radiológicos

O diagnóstico foi confirmado por RT‐PCR em 72 pacientes (todos os 79 testados, 91% positivos). Os demais tiveram o diagnóstico confirmado pela detecção de anticorpos IgM e/ou IgG (cinco no grupo MIS) (tabela 2). Houve codetecção com outros vírus em 15% dos testados (dois vírus sincicial respiratório, um rinovírus humano e um uma associação de Parainfluenza 4 com Bordetella pertussis) (tabela 2).

Tabela 2.

Confirmação diagnóstica, achados laboratoriais e radiológicos de pacientes pediátricos com COVID‐19

    Não MIS(n = 69)MIS(n = 10) 
Diagnóstico etiológico, Número testado (No.)  NoPositivo, No. (%)  NoPositivo, No. (%)  NoPositivo, No. (%) 
Infecção por SARS‐CoV‐2
RT‐PCR  69  67 (85)  10  5 (50)  79  72 (91) 
Sorologia             
IgM  4 (80)  1 (13)  13  5 (45) 
IgG  3 (60)  5 (63)  13  8 (62) 
IgM e IgG  2 (40)  0 (0)  13  1 (8) 
Codetecção com COVID‐19             
Teste rápido para vírus sincicial respiratório  25  2 (8)  0 (0)  26  2 (8) 
Outro vírus  18  2 (11)  0 (0)  21  2 (10) 
Rinovírus humano  1 (50)  0 (0)  1 (50) 
Parainfluenza 4+Bordetella parapertussis  1 (50)  0 (0)  1 (50) 
Exame de sangue, Número testado (No.)  NoValoresMediana (IIQ)    ValoresMediana (IIQ)  NoValoresMediana (IIQ) 
Contagem total de leucócitos (x1.000/μL)  66  11.850 (7.933‐18.075)  10  18.275 (14.293‐ 23.868)  76  12.520 (8.382‐19.100) 
Contagem deplaquetas(x1,000/μL)  66  260.500 (159.250‐374.500)  10  103.000 (78.750‐177.500)  76  226.500 (136.750‐367.000) 
Linfopenia No. (%)  59  21 (36)  10  5 (50)  69  26 (38) 
Proteína C‐reativa (mg/dL),  63  3 (0.6‐18)  10  10 (9‐30)  73  5.1 (0.7‐20.0) 
Velocidade de hemossedimentação (mm/1ah)  68 (45‐85)  100 (49‐120)  14  88 (46‐115) 
Desidrogenase láctica (U/L)  30  395 (290‐612)  630 (545‐844)  38  433 (294‐737) 
D‐Dímero (ng/mL)  22  1.723 (441‐3.966)  3.755 (2.170‐5.099)  30  1.953 (1.099‐4.099) 
Procalcitonina (ng/mL)  0,4 (0,4‐0,4)  15,7 (8‐23,3)  0,4 (0,4‐15,7) 
Ureia (mg/dL)  58  23 (16‐35)  10  33 (22‐45)  68  24 (16‐38) 
Creatinina (mg/dL)  59  0,4 (0,3‐0,6)  10  0,5 (0,4‐0,7)  69  0,5 (0,3‐0,6) 
Albumina (g/dL)  36  3,2 (2‐ 4)  2,8 (2,4‐3,2)  42  3,2 (2,3‐3,8) 
Alanina aminotransferase (U/L)  49  28 (15‐55)  54 (41‐70)  58  41 (15‐57) 
Aspartato aminotransferase (U/L)  49  40 (31‐75)  10  51 (29‐67)  59  42 (31‐73) 
Creatinaquinase, total (U/L)  14  72 (35‐347)  67 (47‐147)  22  68 (44‐170) 
Creatina quinase, banda miocárdica (U/L)  12  27 (22‐46)  20 (11‐24)  15  26 (21‐42) 
Troponina (ng/mL)  0,4 (0‐5)  0,0 (0,0‐0,4)  17  0,1 (0,0‐1,0) 
Ferritina (ng/mL)  17  648 (198‐974)  228 (143‐1.366)  24  594 (190‐1.030) 
ProBNP (pg/mL)  ‐  ‐  5.829 (2.962‐10.027) 
Interleucina‐6 (pg/mL)  ‐  453 (323‐582)  453 (323‐582) 
Achados radiológicos na admissão na UTIP  NoImagens alteradas    Imagens alteradas    Imagens alteradas 
Radiografias torácicas anormais  58  35 (60)  10  7 (70)  68  42 (62) 
Infiltrado intersticial difuso, bilateral  35  21 (60)  4 (57)  42  25 (60) 
Infiltrado intersticial, localizado  35  6 (17)  0 (0)  42  6 (14) 
Consolidação  35  5 (14)  2 (29)  42  7 (17) 
Atelectasia  35  3 (9)  0 (0)  42  3 (7) 
Derrame pleural  35  3 (9)  3 (43)  42  6 (14) 
Hiperinsuflação  35  4 (11)  0 (0)  42  4 (10) 
TC de tórax com opacidades em vidro fosco  31  18 (58)  1 (14)  38  19 (50) 

COVID‐19, doença do coronavírus 2019; SARS‐CoV‐2, síndrome respiratória aguda grave do coronavírus 2; RT‐PCR, reação em cadeia da polimerase com transcrição reversa; IgM, imunoglobulina M; IgG, imunoglobulina G; IIQ, intervalo interquartil; proBNP, peptídeo natriurético do tipo Pro‐B; UTIP, Unidade de Terapia Intensiva Pediátrica, TC, Tomografia computadorizada.

Linfopenia foi observada em 36% dos pacientes no grupo não MIS (MIS, 50%). A proteína C reativa (PCR) foi de 3mg/dL ou superior em 50% dos 63 pacientes do grupo não MIS, em comparação com 10mg/dL ou superior em 50% dos 10 pacientes do grupo MIS. A velocidade de hemossedimentação (VHS), a desidrogenase láctica (LDH) e o D‐dímero foram testados em 5, 30 e 22 pacientes, respectivamente, no grupo não MIS e quase todos os pacientes no grupo MIS. Eles estavam aumentados em pelo menos 75% de todos os pacientes, mas muito mais altos no grupo MIS. Em contraste, as funções renal e hepática foram testadas na maioria dos pacientes e estavam preservadas em pelo menos 75% delas nos dois grupos. A ferritina e a troponina foram testadas em apenas 24 e 17 pacientes, respectivamente, a maioria deles no grupo MIS. A ferritina estava aumentada em pelo menos 50% dos pacientes e foi maior no grupo não MIS. A troponina estava elevada em pelo menos 50% dos pacientes do grupo não MIS, mas não no grupo MIS. Dos outros marcadores de lesão cardíaca, a creatinofosfoquinase (CK) apresentou anormalidade em 5 dos 22 pacientes (408‐2.345 U/L) e a creatinofosfoquinase fração MB (CK‐MB) estava elevada em 8 dos 15 pacientes (25 e 89 U/L). Apenas um desses pacientes estava no grupo MIS (síndrome do choque tóxico, CK 1.389 U/L, CK‐MB 28 U/L). O peptídeo natriurético do tipo B (pro‐BNP) estava aumentado em 6 dos 7 (86%) pacientes testados, todos no grupo MIS, com uma mediana de 5.829 (variação de 222‐16.996 pg/mL). A procalcitonina foi investigada em apenas três pacientes e estava elevada em todos (um no grupo não MIS, 0,4 ng/mL; dois no grupo MIS: uma disfunção cardíaca aguda, 0,37 ng/mL e uma síndrome de choque tóxico, 31 ng/mL). Por fim, a interleucina‐6 foi mensurada em apenas dois pacientes do grupo MIS, ambos com valores muito altos, em um paciente com disfunção cardíaca aguda (711 pg/mL) e um com síndrome de choque tóxico (194 pg/mL) (tabela 2)

A radiografia de tórax mostrou anormalidades em 60‐70% dos pacientes nos dois grupos, com predominância do infiltrado intersticial difuso bilateral (57‐60%). O derrame pleural estava presente em sete pacientes (43%) no grupo MIS e em apenas três pacientes (9%) no grupo não MIS. Trinta e oito pacientes foram submetidos à tomografia computadorizada (TC) de tórax e opacidades em vidro fosco estavam presentes em 58% no grupo não MIS e em apenas 14% no grupo MIS (tabela 2).

Manejo e resultados clínicos

Cinquenta e um de todos os pacientes (65%) precisaram de algum tipo de suporte ventilatório: 32 (41%) usaram apenas oxigenoterapia, cinco (6%) precisaram apenas de ventilação não invasiva (VNI) e 14 (18%) necessitaram de VMI. Nos pacientes que necessitaram de VMI, 10 (71%) apresentavam síndrome do desconforto respiratório agudo (SDRA), dos quais seis foram classificados como graves, exigiram bloqueio neuromuscular (n=6), manobra de recrutamento alveolar (n=4) e posição prona intermitente (n = 3) Dois desses pacientes desenvolveram hipertensão arterial pulmonar. A mediana de duração da VMI foi de 7,5 dias (IIQ 5‐10) e a mediana da pressão expiratória final positiva (PEEP) mais alta foi de 9,5 cmH2O (IIQ 7‐12). Um desses casos graves de SDRA estava no grupo MIS (tabela 3).

Tabela 3.

Manejo e resultados clínicos de pacientes pediátricos com COVID‐19

  Não MIS‐Cn = 69  MIS‐Cn = 10  Totaln = 79 
Manejo e desfechos  No. (%) ou Mediana (IIQ)  No. (%) ou Mediana (IIQ)  No. (%) ou Mediana (IIQ) 
Apenas oxigenoterapia  28 (41)  4 (40)  32 (41) 
Apenas ventilação não invasiva  4 (6)  1 (10)  5 (6) 
Ventilação mecânica invasiva  13 (19)  1 (10)  14 (18) 
Dias de uso, mediana (IIQ)  8,0 (6,0, 11,0)  5,0 (5,0, 5,0)  7,5 (5,0, 10,0) 
PEEP mais alta, mediana (IIQ)  9,0 (7,0, 11,0)  12,0 (12,0, 12,0)  9,5 (7,0, 12,0) 
Posição prona intermitente  3 (100)  0 (0)  3 (21) 
Recrutamento alveolar  4 (44)  0 (0)  4 (29) 
Bloqueio neuromuscular  5 (7)  1 (10)  6 (43) 
Diagnóstico de SDRA  9 (13)  1 (10)  10 (13) 
Leve  4 (44)  0 (0)  4 (40) 
Moderada  0 (0)  0 (0)  0 (0) 
Grave  5 (56)  1 (100)  6 (60) 
Hipertensão arterial pulmonar  2 (3)  0 (0)  2 (3) 
Tratamento farmacológico
Antibióticos  52 (75)  8 (80)  60 (76) 
Oseltamivir  32 (46)  2 (20)  34 (43) 
Terapia antifúngica  3 (4)  1 (10)  4 (5) 
Corticosteroides  16 (23)  2 (20)  18 (23) 
Hidroxicloroquina  0 (0)  0 (0)  0 (0) 
UTIP TP, dias, mediana (IIQ)  5,0 (2,8, 10,0)  5,5 (2,8, 7,5)  5,0 (2,2, 10,0) 
Desfechos
Alta hospitalar  62 (90)  9 (90)  71 (90) 
Morte  2 (3)  0 (0)  2 (3) 
Transferência para outro hospital  5 (7)  1 (10)  6 (8) 

SDRA, Síndrome do Desconforto Respiratório Agudo; IIQ, intervalo interquartil; TP, Tempo de permanência; PEEP, pressão expiratória final positiva; UTIP, Unidade de Terapia Intensiva Pediátrica.

Antibióticos foram usados por 76% de todos os pacientes, oseltamivir em 43% e corticosteroides em 23%. Nenhum paciente recebeu hidroxicloroquina (tabela 3). A mediana do tempo de permanência (TP) na UTIP foi de 5 dias (IIQ 2,2‐10) e a maioria dos pacientes recebeu alta (90%). As únicas duas mortes (3% de mortalidade) ocorreram no grupo não MIS, ambos os pacientes com comorbidades graves e uso crônico de corticosteroides (tabela 3). Um caso era uma menina de 14 anos com doença hepática crônica e o outro, uma menina de um ano com doença pulmonar crônica e síndrome do intestino curto.

Subgrupos específicos

O subgrupo de pacientes com comorbidades era significativamente mais velho (média de idade: 7,5 anos vs. 1,8 ano, p 0,01), tinha maior necessidade de oxigenoterapia (56% vs. 31%, p 0,05) e VMI (31% vs. 9%, p 0,01) e diagnóstico mais frequente de SDRA (25% vs. 4%, p 0,01), mas não houve diferenças em relação à duração do suporte respiratório e do TP na UTIP. Nos pacientes que necessitaram de VMI, o TP na UTIP foi significativamente maior (12,0 vs. 5,0 dias, p 0,01). A idade inferior a um ano não determinou uma apresentação clínica diferente. Nos pacientes com MIS, não observamos diferenças significativas entre os pacientes com comorbidades, idade inferior a um ano e necessidade de VMI (tabela 4a). Também comparamos esses três grupos específicos, consideramos apenas pacientes que não apresentavam MIS, mas os resultados foram bastante semelhantes (tabelas S1 e S2, material suplementar).

Tabela 4a.

Dados demográficos e características clínicas de pacientes pediátricos com COVID‐19 de acordo com a presença de comorbidades, idade inferior a um ano e necessidade de ventilação mecânica invasiva em todos os pacientes (n = 79).

Característica  ComorbidadesIdade inferior a um anoVentilação mecânica invasiva
  Sim  Não  p‐valor  Sim  Não  p‐valor  Sim  Não  p‐valor 
Idade, mediana (IIQ), a  7,5 (2,1, 12,4)  1,8 (0,8, 7,0)  0,01c  0,5 (0,2, 0,7)  7,0 (1,9, 12,4)    5,6 (1,2, 10,3)  4,2 (1,2, 10,8)  0,94c 
Sexo, No. (%)
Masculino  17 (53)  26 (55)  1a  9 (47)  34 (57)  0,48  6 (43)  37 (57)  0,51a
Feminino  15 (47)  21 (45)    10 (53)  26 (43)    8 (57)  28 (43) 
Etnia, No. (%)
Branca  17 (53)  29 (62)  0,57a  8 (42)  38 (63)  0,17a  8 (57)  38 (58)  1a
Não branca  15 (47)  18 (38)    11 (58)  22 (37)    6 (43)  27 (42) 
Comorbidades, No. (%)
Sim  ‐  ‐  ‐  5 (26)  27 (45)  0,19a  10 (71)  22 (34)  0,01a
Não  ‐  ‐  ‐  14 (74)  33 (55)    4 (29)  43 (66) 
Principal apresentação, No. (%)
Respiratória  22 (69)  25 (53)  0,11a  13 (68)  34 (57)  0,72a  11 (79)  26 (48)  0,08a 
MIS  2 (6)  8 (17)  0,18b  2 (11)  8 (13)  1b  1 (7)  9 (17)  0,67a 
Condição similar à doença de Kawasaki  2 (100)  4 (50)  0,56b  2 (100)  4 (50)  0,56b  0 (0)  6 (67)  0,30b 
Disfunção cardíaca aguda  0 (0)  2 (25)    0 (0)  2 (25)    0 (0)  2 (22)   
Síndrome do choque tóxico  0 (0)  1 (13)    0 (0)  1 (12)    1 (100)  0 (0)   
Síndrome da ativação de macrófagos  0 (0)  1 (13)    0 (0)  1 (12)    0 (0)  1 (11)   
Outras  8 (25)  14 (30)  0,85a  4 (22)  18 (30)  0,73a  2 (14)  20 (37)  0,12a 
Manejo, No. (%)
Apenas oxigenoterapia  18 (56)  14 (31)  0,05a  5 (26)  27 (45)  0,24a  ‐  32 (49)   
Ventilação não invasiva  3 (9)  2 (4)  0,39b  1 (5)  4 (7)  1a    5 (8)   
Ventilação mecânica invasiva  10 (31)  4 (9)  0,01b  3 (16)  11 (18)  1a  ‐  ‐   
Dias de uso, mediana (IIQ)  7,5 (5,5‐ 9,0)  12,5 (8,8, 16,2)  0,67c  9,0 (9,0‐ 9,0)  7,0 (5,0, 11,0)  0,66c  7,5 (5,0‐ 10,0)  ‐   
Diagnóstico de SDRA, No. (%)  8 (25)  2 (4)  0,01b  1 (5)  9 (15)  0,44b  ‐  ‐  ‐ 
TP UTIP, dias, mediana (IIQ)  5,5 (2,8, 10)  5 (2‐8)  0,88c  6 (4‐11)  5 (2‐9)  0,18c  12 (6‐18)  5,0 (2‐7)  0,01c 
Desfecho, No. (%)
Alta hospitalar  26 (81)  45 (96)  0,10b  17 (89)  54 (90)  0,79b  10 (71)  61 (94)  0,01b 
Morte  2 (6)  0 (0)    0 (0)  2 (3)    2 (14)  0 (0)   
Transferência para outro hospital  4 (12)  2 (4)    2 (11)  4 (7)    2 14)  4 (6)   
  Tabela 4 b ‐ Odds ratio não ajustados e ajustadosd e intervalos de confiança de 95% para pacientes pediátricos com COVID‐19, de acordo com a necessidade de ventilação mecânica invasiva (n = 79)
  Ventilação mecânica invasiva
  Não ajustadoOR (CI 95%)  p‐valor  AjustadoOR (CI 95%)  p‐valor 
Idade < 1 ano  1,00 (0,99‐1,01)  0,69  0,99 (0,99‐1,00)  0,64 
Sexo, masculino  0,57 (0,18‐1,82)  0,34  0,53 (0,15‐1,84)  0,32 
Etnia, não branca  1,06 (0,33‐3,39)  0,93  0,85 (0,24‐2,98)  0,80 
Comorbidades  4,89 (1,37‐17,37)  0,01  5,49 (1,43‐21,12)  0,01 

IIQ, intervalo interquartil; MIS, síndrome inflamatória multissistêmica; SDRA, Síndrome do Desconforto Respiratório Agudo; UTIP, Unidade de Terapia Intensiva Pediátrica; TP, Tempo de permanência; OR, odds ratio; IC, intervalo de confiança; UTIP, Unidade de Terapia Intensiva Pediátrica.

a

Qui‐quadrado.

b

Exato de Fisher.

c

Mann‐Whitney.

d

Ajustado para idade < 1 ano, etnia, sexo e presença de comorbidades.

A análise multivariada mostrou que apenas a presença de comorbidades estava significativamente associada à gravidade, representada pela necessidade de VMI (OR ajustado 5,5; IC95% 1,43‐21,12; p 0,01) (tabela 4b).

Discussão

Que seja de nosso conhecimento, este é o primeiro estudo prospectivo e multicêntrico a relatar características e resultados de crianças com COVID‐19 internadas em UTIPs no Brasil, o atual epicentro da doença na América Latina e o segundo no mundo, depois dos EUA. Embora a maioria das crianças e adolescentes tenha um curso benigno da doença, demonstramos que alguns pacientes podem desenvolver condições clínicas agudas graves, especialmente aquelas com comorbidades anteriores, e posteriormente também apresentam MIS.

Em nossa coorte, embora a mediana de idade fosse de quatro anos e um quarto dos pacientes fosse lactente, 44% eram crianças em idade escolar, adolescentes e adultos jovens, um percentual superior ao geralmente observado nas UTIPs brasileiras para essa faixa etária, geralmente em torno de 25%.9 Isso é semelhante ao relatado por um grande estudo europeu10 e por UTIPs americanas, que relataram uma porcentagem ainda maior de hospitalizações nessa faixa etária (70%).2,11 Não observamos uma grande diferença entre as medianas das idades dos grupos MIS e não MIS, embora nosso número de pacientes com MIS tenha sido pequeno. Quanto ao sexo, não houve diferenças no grupo não MIS, enquanto nos pacientes com MIS houve predomínio masculino de 4:1, diferentemente do relatado por outros autores.12,13 Houve uma pequena predominância de pacientes de etnia branca (58‐60%), o que está em contraste com a predominância da população brasileira, que é de 56% de não brancos. Entretanto, cerca de metade dos pacientes era de hospitais particulares, acessíveis apenas à população de renda média e alta, onde os brancos são a maioria.

As comorbidades têm sido descritas como um importante fator de risco para casos mais graves de COVID‐19 em crianças, representam entre 50‐80% das admissões em UTIP.11,14,15 Embora tivéssemos uma porcentagem um pouco menor desses pacientes (41%), eles eram significativamente mais velhos e tinham uma apresentação significativamente mais grave (mais SDRA, mais suporte ventilatório, mais VMI). O modelo de regressão logística mostrou que as comorbidades estavam independentemente associadas à necessidade de VMI, com um odds ratio ajustado de 5,5 [IC95%, 1,4‐21,1). Doença neuromuscular, doença respiratória crônica e doença onco‐hematológica foram as comorbidades mais prevalentes em nossa coorte, o que é um pouco diferente de outros relatos em terapia intensiva pediátrica.5,11,14,15

Somente cerca de 40% dos pacientes tinham histórico prévio de contato com um caso suspeito, principalmente em casa, o que é semelhante a outros relatos.4 A febre foi o sintoma predominante, seguido por vários sinais e sintomas respiratórios e gastrointestinais, que não diferiram do que foi relatado em outros estudos.5,10,14,16 Houve maior prevalência de sintomas gastrointestinais no grupo MIS, como diarreia e vômito com desidratação, o que também foi observado por outros autores.12,13 O intervalo entre o início dos sintomas e a hospitalização foi menor no grupo MIS (mediana, 2 vs. 5 dias). Isso pode ser explicado pelos casos mais graves nesse grupo, alguns deles apresentaram sinais de choque e insuficiência cardiorrespiratória. Embora a principal síndrome clínica na hospitalização fosse geralmente de origem respiratória ou gastrointestinal, tivemos 10 pacientes (13%) internados na UTIP por causa da MIS. Esse é um fenômeno novo relacionado à COVID‐19 em crianças e espera‐se que muitos desses pacientes precisem de acompanhamento na UTIP e também por outras especialidades pediátricas.6

A maioria dos nossos pacientes teve seu diagnóstico confirmado por RT‐PCR (91%), mas observamos uma proporção maior de resultados negativos no grupo MIS (50% vs. 15%). Isso é compatível com dados anteriores, mostra que a MIS é uma manifestação tardia associada ao COVID‐19, fora da janela de positividade para a RT‐PCR. Nesse grupo, a associação com uma infecção por SARS‐CoV‐2 foi observada em metade dos pacientes através de sorologia positiva, principalmente IgG. Por outro lado, no grupo não MIS, uma IgM positiva foi detectada em 80% dos poucos casos nos quais foi medida. A codetecção com outros vírus foi observada em 15% dos pacientes nos quais foi investigada (apenas no grupo não MIS), semelhante a outros estudos da COVID‐195,10 e em outras infecções graves por vírus respiratórios em crianças.17

A linfopenia foi observada em geral em 38% dos pacientes (50% no grupo MIS), o que também já foi descrito em outros estudos pediátricos da COVID‐19.5,14,15,18 Embora alguns estudos em adultos tenham associado linfopenia a um prognóstico ruim,19,20 isso ainda não está claro na pediatria. Marcadores inflamatórios, como VHS, PCR, LDH, D‐Dímero, procalcitonina e ferritina, estavam elevados na maioria dos pacientes testados, mas principalmente no grupo MIS, o que está de acordo com os critérios diagnósticos para essa síndrome.21–23 Em nossa coorte, medimos a troponina, CK e CK‐MB em menos de 20% dos pacientes e encontramos níveis elevados em pelo menos 50% deles. Esses biomarcadores de lesões cardíacas também foram relatados com níveis anormais em outros estudos, principalmente em pacientes com algum tipo de insuficiência cardíaca.12–14 Outro marcador sensível conhecido para detecção de insuficiência cardíaca, o ProBNP, estava elevado em todos os sete pacientes nos quais foi medido no grupo MIS, como também relatado em outros estudos.6,24 Também medimos a interleucina‐6 (IL‐6) em dois pacientes do grupo MIS, ambos com disfunção cardíaca grave e choque e níveis muito altos foram encontrados. Níveis elevados já foram descritos em pacientes pediátricos críticos com COVID‐19.5,8,12

Outro achado consistente com disfunção cardíaca em pacientes do grupo MIS foi derrame pleural, detectado por radiografia de tórax, uma característica muito menos frequente no grupo não MIS. Os outros achados radiológicos de infiltrados intersticiais difusos bilaterais e opacidades em vidro fosco, nas radiografias de tórax e na TC, estavam presentes na maioria dos pacientes, o que é consistente com relatos anteriores.10,18,25

Quanto ao manejo dos pacientes, a maioria necessitou de algum tipo de suporte respiratório; a maioria necessitou apenas de oxigenoterapia, mas cerca de 20% necessitaram de VMI (mediana de 7,5 dias), o que está dentro da faixa de uso relatada (18‐50%) descrita em outros estudos.5,10,11,14 Desses, 71% desenvolveram SDRA, principalmente grave, exigiram bloqueio neuromuscular, PEEP alta, manobra de recrutamento alveolar e posição prona em alguns casos. Embora não pudéssemos confirmar infecções bacterianas, a antibioticoterapia foi usada em três quartos dos pacientes e o oseltamivir em quase metade, o que pode ser explicado pelas diretrizes nacionais para o tratamento da SARS, que indicam o uso inicial do oseltamivir empírico.26 A hidroxicloroquina não foi prescrita, embora alguns estudos tenham relatado seu uso em 7 a 47% dos pacientes.5,10,11,14 Talvez essa diferença possa ser explicada pelo fato de os casos na Europa e nos EUA terem começado semanas ou meses antes do Brasil, quando um uso mais compassivo de drogas poderia ser explicado e também menos estudos estavam disponíveis.

Comparamos as características demográficas e clínicas de acordo com a presença de comorbidades, idade abaixo de um ano e necessidade de VMI. Embora nossos números nesses subgrupos fossem pequenos, encontramos diferenças significativas determinadas pela presença de comorbidades. Esses pacientes eram mais velhos e precisavam de mais suporte respiratório, com a maioria dos casos de SDRA. As únicas duas mortes também ocorreram nesse grupo. A presença de comorbidades aumentou de forma independente a chance de VMI, mas os fatores associados a um pior prognóstico precisam de mais investigação. A obesidade, relatada como o pior fator prognóstico em crianças com COVID‐19,5,11 não foi frequente em nossa coorte, na qual as principais comorbidades significativas foram doenças neuromusculares, doenças respiratórias crônicas e câncer. Idade inferior a um ano, sexo e etnia não foram associados a casos mais graves em nosso estudo, embora os lactentes tenham apresentado pior curso clínico na China e nos EUA.1,2 Como a MIS é uma doença pouco compreendida, que parece ocorrer em uma fase subaguda da infecção por SARS‐CoV‐2, também fizemos as mesmas comparações de subgrupos e a avaliação de preditores de gravidade apenas no grupo não MIS, mas os resultados não diferiram. Como também demonstrado em todos os estudos pediátricos sobre a COVID‐19, a grande maioria dos nossos pacientes progrediu bem e recebeu alta, com uma taxa de mortalidade de apenas 3%.

Nosso estudo tem algumas limitações. Como incluiu apenas pacientes brasileiros, isso pode limitar a generalização de nossos resultados. Além disso, faltam alguns detalhes sobre o tratamento, como o motivo do alto percentual de uso de antibióticos ou corticosteroides. Nem todos os pacientes tiveram os marcadores inflamatórios medidos; portanto, eles não puderam ser comparados dependendo da gravidade da doença. Apesar dessas limitações, acreditamos que nosso estudo pode contribuir para uma melhor compreensão da COVID‐19, pois descreve a primeira grande série de pacientes internados em UTIPs no hemisfério sul.

Mostramos que as características dessa doença em locais tropicais e subtropicais são semelhantes às de outros países. Em nossa coorte, a letalidade foi baixa e as doenças crônicas e outras comorbidades desempenharam um papel importante no desenvolvimento de formas graves da doença. Diferentemente de outros estudos, a idade inferior a um ano não foi associada a um pior prognóstico. Pacientes com MIS apresentaram sintomas mais graves, níveis mais altos de biomarcadores inflamatórios e maior predomínio do sexo masculino.

Financiamento

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), processo n° 401597/2020‐2. Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (Faperj), processo n° E‐26/010.000160/2020, concessão n° 2020/0996.

Conflitos de interesse

Os autores declaram não haver conflitos de interesse.

Agradecimentos

Ana Carolina Cabral P Scarlato ‐ Hospital Rios D’Or; Rodrigo Moulin Silva ‐ Hospital Pedro Ernesto (Uerj); Camila Furtado Guedes Pinto ‐ Hospital Pedro Ernesto (Uerj); Mariana Barros Genuíno de Oliveira ‐ Instituto D’Or de Pesquisa e Ensino (Idor); Jaqueline Rodrigues Robaina ‐ Instituto D’Or de Pesquisa e Ensino (Idor).

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Como citar este artigo: Prata‐Barbosa A, Lima‐Setta F, Santos GR, Lanziotti VS, Castro RE, Souza DC, et al. Pediatric patients with COVID‐19 admitted to intensive care units in Brazil: a prospective multicenter study. J Pediatr (Rio J). 2020;96:570.

Estudo vinculado à Rede Brasileira de Pesquisa em Medicina Intensiva Pediátrica (BRnet‐PIC), Brasil.

Copyright © 2020. Sociedade Brasileira de Pediatria
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