Fernandes DM, Oliveira CR, Guerguis S, Eisenberg R, Choi J, Kim M, et al. Tri-State Pediatric COVID-19 Research Consortium. Severe Acute Respiratory Syndrome Coronavirus 2 Clinical Syndromes and Predictors of Disease Severity in Hospitalized Children and Youth. J Pediatr 2021;230:23-31.e10.
Question
Among hospitalized children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and/or multisystem inflammatory syndrome in children (MIS-C), what are the predictors for severe disease?
Design
Multicenter, retrospective, and prospective cohort study.
Setting
8 sites in New York, New Jersey, and Connecticut.
Participants
Children and youth <22 years of age, with laboratory-confirmed SARS-CoV-2 infection or MIS-C.
Intervention
Multivariable logistic regression models were fit to the cohort data.
Outcomes
Severity of disease predictors.
Main Results
Of 281 patients, 51%/25%/25% had respiratory disease/MIS-C/other manifestations (including gastrointestinal illness or fever). In multivariate analyses, obesity (OR 3.4, 95% CI 1.3-9.1) and hypoxia at admission (OR 4.01, 95% CI 1.1-14.2) were associated with severe disease; lower absolute lymphocyte count (OR 8.33 per unit decrease in 109 cells/L, 95% CI 2.3-33.3) and greater C-reactive protein (OR 1.06 per unit increase in mg/dL, 95% CI 1.0-1.1) were associated with MIS-C. Race was not associated with severe disease.
Conclusions
Multivariate analysis identified several variables associated with developing severe disease and MIS-C.
Commentary
Pediatric COVID-19 is now well recognized to be less severe compared with adults. However, important gaps exist in identifying both diverse clinical sequelae and risk factors for severe disease. This well-done study is a step in the direction of resolving some of the gaps. Fernandes et al performed meticulous clinical and laboratory characterization of clinical phenotypes and outcomes from a large multicenter cohort. The results corroborate some existing hypotheses—obesity as a risk factor for severity similar to older adults, different underlying risk profiles for severe, acute COVID-19 vs MIS-C (fewer comorbidities in the latter), and the prognostic importance of immune response characterization in hospitalization (lymphopenia and inflammatory markers). The choice of study outcome—ICU admission—could have led to variability between centers in terms of the threshold for more intensive observation (eg, lower for infants). It would be interesting to see predictors of related outcomes, such as oxygen requirement or vasoactive support. Age in the analysis is modeled as a continuous variable. It may help further work to look at age categories (eg, infants vs adolescents) particularly because it may interact with other variables (eg, severity of underlying complex conditions or obesity). Race and ethnicity were not statistically significant in the multivariable analysis. However, the striking preponderance of these hospitalized cases were non-white, and this geographically spread-out sample highlights the absolute difference in burden for minority communities. The study does point to some laboratory and imaging results that, at admission, may indicate a more severe course. Yet challenges remain, especially in predicting the disease trajectory earlier in the disease course, before the onset of significant hypoxia or cardiac injury (in MIS-C).