125 - Exploring Viral and Host Determinants of COVID-19 Severity in a Diverse Pediatric Cohort

Publication Number: 125.4814

Thomas T. Barter, Children's Hospital Los Angeles, Costa Mesa, CA, United States; Carly Weaver, Children’s Hospital Los Angeles, Los Angeles, CA, United States; Dejerianne Ostrow, CHLA, LA, CA, United States; Jennifer Dien Bard, Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States; Xaiowu Gai, Medical College of Wisconsin, Milwaukee, WI, United States; Sindhu Mohandas, Children's Hospital Los Angeles, Los angeles, CA, United States

Background: COVID-19 has been in the global spotlight since 2019, impacting billions of lives globally. Numerous studies have been conducted to better our understanding of COVID-19 and its effect on individuals and our healthcare systems. Despite this, many facets of COVID-19 remain unknown. Specifically, reasons attributed to the variation in severity across patients.

Objective: Here we investigated whether different strains of SARS-CoV-2 alongside host factors including race or ethnicity contribute to the overall disease severity and outcome in pediatric patients at a quaternary care, free standing pediatric medical center.

Design/Methods: Data was pulled from electronic health records at Children’s Hospital Los Angeles from March 2020 to March 2024 and the severity of COVID-19 for each patient was scored using a modified ordinal severity scale. SARS-CoV-2 strain was determined through viral whole genome sequencing. Multinomial logistic regression was employed to determine if viral variant or other host factors had a significant impact on COVID-19 severity.

Results: We found that Omicron has a significant increase in moderate (Odds: Ratio 2.78) and severe (OR: 3.96) cases when compared to the earlier variants. White patients have a lower chance of having moderate (OR: 0.81) or severe (OR: 0.82) disease when compared to non-White patients. Specifically, Hispanic, Asian, and African American were more likely to have severe disease when compared to White patients, but there was no significant difference in severity when non-White groups are compared to each other. Overall, younger children are more likely to have moderate or severe disease. However, when patients with SARS-CoV-2 genotypes were studied, we found no significant relationship between age and most variants except Delta, which was more likely to be severe in older patients (Fig 1). Each race had their own unique age-specific effects on disease severity suggesting that age and race of the patient have a unique interaction on severity. When considering Ethnicity on variant severity, Hispanic populations were more likely to have moderate to severe disease with the Ancestral strain. However, with Omicron this trend was reversed, and Hispanic patients were less likely to have moderate to severe disease (Fig 2).

Conclusion(s): Based on our data, it appears that host factors like age, race and ethnicity and SARS-CoV-2 variants play an important role in determining severity for pediatric COVID-19. Viral variants exhibit differential impacts on children across racial and ethnic groups, indicating a substantial influence of patient genetic factors on variant virulence.

Breakdown of pediatric patient population and severity at Children's Hospital Los Angeles
Summary data of pediatric patient population broken down by age, race, sex, and if SAR-CoV-2 variant is available for each severity metric.

Age-specific effect of SARS-CoV-2 variant on severity
Each line represents the probability of having a given severity score across all ages for each SARS-CoV-2 variant. Probability for each severity metric is determine by multinomial logistic regression model. "nVoC" stands for non-variant of concern, which is a culmination of variants not described as a variant of concern by WHO.

Comparison of COVID-19 severity when accounting for Ethnicity and SARS-CoV-2 variant
Comparison of the frequency of moderate and severe cases for each SARS-CoV-2 variant and Ethnicity combination.