Risk factors for severe PCR-positive SARS-CoV-2 infection in hospitalized children: a multicenter cohort study
Authors: Schober Tilmann , Caya Chelsea , Barton Michelle , Bayliss Ann , Bitnun Ari , Bowes Jennifer , Brenes-Chacon Helena , Bullard Jared , Cooke Suzette , Dewan Tammie , Dwilow Rachel , Tal Tala El , Foo Cheryl , Gill Peter , Aski Behzad Haghighi , Kakkar Fatima , Lautermilch Janell , Laxer Ronald M. , Lefebvre Marie-Astrid , Leifso Kirk , Saux Nicole Le , Lopez Alison , Manafi Ali , Morris Shaun K. , Nateghian Alireza , Panetta Luc , Petel Dara , Piché Dominique , Purewal Rupeena , Restivo Lea , Roberts Ashley , Sadarangani Manish , Scuccimarri Rosie , Soriano-Fallas Alejandra , Tehseen Sarah , Top Karina A. , Ulloa-Gutierrez Rolando , Viel-Thériault Isabelle , Wong Jacqueline K. , Yea Carmen , Yeh Ann , Yock-Corrales Adriana , Robinson Joan , Papenburg Jesse 
Published: October 2021

AbstractImportanceChildren are less likely than adults to have severe outcomes from SARS-CoV-2 infection and the corresponding risk factors are not well established.ObjectiveTo identify risk factors for severe disease in symptomatic children hospitalized for PCR-positive SARS-CoV-2 infection.DesignCohort study, enrollment from February 1, 2020 until May 31, 2021Setting15 children’s hospitals in Canada, Iran, and Costa RicaParticipantsPatients <18 years of age hospitalized with symptomatic SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C)ExposuresVariables assessed for their association with disease severity included patient demographics, presence of comorbidities, clinical manifestations, laboratory parameters and chest imaging findings.Main Outcomes and MeasuresThe primary outcome was severe disease defined as a WHO COVID-19 clinical progression scale of ≥6, i.e., requirement of non-invasive ventilation, high flow nasal cannula, mechanical ventilation, vasopressors, or death. Multivariable logistic regression was used to evaluate factors associated with severe disease.ResultsWe identified 403 hospitalizations. Median age was 3.78 years (IQR 0.53-10.77). At least one comorbidity was present in 46.4% (187/403) and multiple comorbidities in 18.6% (75/403). Severe disease occurred in 33.8% (102/403). In multivariable analyses, presence of multiple comorbidities (adjusted odds ratio 2.24, 95% confidence interval 1.04-4.81), obesity (2.87, 1.19-6.93), neurological disorder (3.22, 1.37-7.56), anemia, and/or hemoglobinopathy (5.88, 1.30-26.46), shortness of breath (4.37, 2.08-9.16), bacterial and/or viral coinfections (2.26, 1.08-4.73), chest imaging compatible with COVID-19 (2.99, 1.51-5.92), neutrophilia (2.60, 1.35-5.02), and MIS-C diagnosis (3.86, 1.56-9.51) were independent risk factors for severity. Comorbidities, especially obesity (40.9% vs 3.9%, p<0.001), were more frequently present in adolescents ≥12 years of age. Neurological disorder (3.16, 1.19-8.43) in children <12 years of age and obesity (3.21, 1.15-8.93) in adolescents were the specific comorbidities associated with disease severity in age-stratified adjusted analyses. Sensitivity analyses excluding the 81 cases with MIS-C did not substantially change the identified risk factors.Conclusions and RelevancePediatric risk factors for severe SARS-CoV-2 infection vary according to age and can potentially guide vaccination programs and treatment approaches in children.Key pointsQuestionWhat are the risk factors for severe disease in children hospitalized for PCR-positive SARS-CoV-2 infection?FindingsIn this multinational cohort study of 403 children, multiple comorbidities, obesity, neurological disorder, anemia, and/or hemoglobinopathy, shortness of breath, bacterial and/or viral coinfections, chest imaging compatible with COVID-19, neutrophilia, and MIS-C diagnosis were independent risk factors for severity. The risk profile and presence of comorbidities differed between pediatric age groups, but age itself was not associated with severe outcomes.MeaningThese results can inform targeted treatment approaches and vaccine programs that focus on patient groups with the highest risk of severe outcomes.