Impact of SARS-CoV-2 variants and demographic factors on COVID-19 severity in pediatric patients

BACKGROUND: Factors that influence pediatric COVID-19 severity remain incompletely understood, particularly related to the impact of viral and host factors. Understanding the factors contributing to the severity of presentation can impact clinical approaches and management. This study examined the associations between SARS-CoV-2 variants, demographic factors, and COVID-19 severity in a large diverse pediatric population. METHODS: We conducted a retrospective cohort study at a large freestanding Children's Hospital (Children's Hospital Los Angeles) from March 2020 through April 2024 including 14,292 patients aged 0-25 years who tested positive for SARS-CoV-2. Viral variants were determined by whole genome sequencing in 6,939 patients (48.6%). COVID-19 severity was classified as mild, moderate, or severe based on hospitalization requirements and need for respiratory support following the World Health Organization Criteria. Disease severity comparisons were made between different viral variants and demographic factors using multinomial logistic regression. RESULTS: Among 14,292 patients, 53.8% were male with median age 5.2 years. Racial/ethnic distribution was 63.0% Hispanic/Latino, 21.4% White, 9.3% African American, and 6.3% Asian. Compared with pre-Omicron variants, Omicron was associated with increased odds of moderate (odds ratio [OR], 2.85; 95% CI, 2.31-3.52; P < 0.001) and severe disease (OR, 3.95; 95% CI, 3.01-5.18; P < 0.001). White patients had lower odds of moderate (OR, 0.81; 95% CI, 0.67-0.98) and severe disease (OR, 0.82; 95% CI, 0.64-1.05) compared with non-White patients. Age-race interactions were significant, with different severity patterns across racial groups as age increased. CONCLUSIONS: Our findings suggest that both viral variants and host demographic factors contribute meaningfully to pediatric COVID-19 severity. Understanding these interactions would support a more tailored approach to pediatric COVID-19 that considers the impact of viral variants and host demographic factors.