Severe COVID-19 outcomes in pediatrics: An observational cohort analysis comparing Alpha, Delta, and Omicron variants.

Objective: COVID-19 can rarely lead to severe illness in pediatric patients. The aim of this study was to determine if severe outcomes in pediatric COVID-19 have changed over the course of the pandemic. Methods: This was a multicenter, observational cohort analysis from a large regional healthcare system in metro Detroit using electronic health record data to evaluate emergency visits, hospitalization, and severe COVID-19 disease in pediatric patients. Consecutive pediatric patients presenting to the emergency department with a primary diagnosis of COVID-19 were included. Outcomes data was gathered from three distinct time intervals that coincided with Alpha, Delta, and Omicron variant predominance (Time interval 1 (T1) 1/1/2021-6/30/2021: Alpha, T2 7/1/2021-12/31/2021: Delta, T3 1/1/2022-6/16/2022): Omicron. The primary outcome was severe disease inclusive of composite intensive care unit admission, mechanical ventilation, multisystem inflammatory syndrome in children (MIS-C), myocarditis, or death. Secondary outcomes included severe outcomes considering viral coinfection and vaccination status. Results: Between 1/1/2021 and 6/16/2022, there were 4517 emergency COVID-19 visits, of which 12.5% (566) of children were hospitalized. 24.4% (138), 31.6% (179), and 44.0% (249) of admissions occurred during T1, T2 and T3 respectively. Most patients were male (55.1%) and 59.9% identified as Caucasian. The median age was 5.0 (interquartile range 1.0, 13.0) with infants comprising 22.8% (129), toddlers 25.1% (142), children 23.0% (130), and teenagers 29.2% (165). Over the course of the pandemic, the proportion of infants in hospitalization increased from 16.7% in T1 to 19.6% in T2 to 28.5% in T3 (p < 0.01) while the proportion of teenagers in hospitalization decreased from 39.1% in T1 to 31.3% in T2 to 22.1% in T3 (p < 0.001). Oxygen therapy was required in a minority (29.9%) of cases with supplemental oxygen utilized the least in T3 (16.5%) and most in T2 (30.2%). Composite severe disease decreased throughout the pandemic occurring in 36.2% in T1, 27.4% in T2, and 18.9% in T3. A multivariable logistic regression analysis revealed the odds of composite severe disease was significantly lower in T3 compared to T1 (adjusted odds ratio [aOR] 0.35, 95% Confidence Interval 0.21-0.60, p < 0.001). Fully vaccinated or fully vaccinated and boosted admission rates remained low throughout all periods with 4.4% in T1, 4.5% in T2 and 8.4% in T3. Viral coinfection was most common during T2 (16.8%) followed by T3 (12.5%) and least common in T1 (5.1%) (p = 0.006). Coinfection occurred more commonly in younger children with a median age of 1.2 (0.0, 4.5) compared to those with mono-infection with a median age of 6 (1.0, 14.0) (p < 0.001). Severe outcomes occurred in 45.6% of coinfection cases compared to 22.1% without coinfection (p < 0.001). Conclusions: While Omicron cases had the highest admission frequency, severe illness was lower than Delta and Alpha variants. Coinfection with respiratory viruses increased the risk of severe outcomes and impacted infants more than older children. Funding: None.