Pediatric SARS-CoV-2 seroprevalence higher than official case reports

By Neha MathurReviewed by Benedette Cuffari, M.Sc.Apr 3 2023

In a recent article published by the United States of America Centers for Disease Control and Prevention (CDC) Emerging Infectious Diseases online journal, researchers conducted a cross-sectional survey to estimate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in children with confirmed coronavirus disease 2019 (COVID-19) between May and July 2021 in Colorado.

Study: SARS-CoV-2 seroprevalence compared with confirmed COVID-19 cases among children, Colorado, USA, May–July 2021. Image Credit: Prostock-studio / Shutterstock.com

Background

Several epidemiologic studies have demonstrated that, as compared to adults, COVID-19 outcomes are less severe in children. However, since this disease is often asymptomatic or mildly symptomatic in children, relying on reported viral testing as the primary source of surveillance data might have led to an underestimation of the disease burden in the pediatric population.

Thus, there is an urgent need for laboratory assays to detect SARS-CoV-2 immunoglobulin G (IgG) to capture more accurate and refined estimates of the true prevalence of SARS-CoV-2 infections in children.

About the study

In the present study, researchers first collected residual serum samples from all eligible children. Then, these samples were tested for SARS-CoV-2 nucleocapsid (N) and spike (S) IgG using qualitative enzyme-linked immunosorbent assay (ELISA).

Children were stratified based on age into three groups, with children in the first, second, and third groups falling into age groups of one to four, five to 11, and 12 to 17 years, respectively. Each child's age, gender, and race/ethnicity were retrieved from their electronic medical record (EMRs). Racial/ethnic groups were assigned based on self-reported ethnicities as Hispanic, non-Hispanic White, non-Hispanic Black, other, and unknown.

For SARS-CoV-2 seroprevalence estimates, the number of specimens positive for SARS-CoV-2 N and S IgGs, or both, was divided by total specimens in a sample of unvaccinated children.

Seropositive case ascertainment reflected the number of seropositive individuals identified as confirmed cases divided by the number of seropositive individuals. In addition, the researchers calculated multiplication factors, i.e., the number of infections per reported case, as the inverse of case ascertainment.

Study findings

The final study sample comprised 829 children, 422 of whom were female, with an average age was nine years. A total of 940 distinct residual serum samples were obtained from these children aged between one to 17 years during the spring/summer season of 2021.

The seroprevalence of IgG against SARS-CoV-2 S was 36.7%, thus suggesting that the SARS-CoV-2 S IgG response might be more durable than the N IgG response.

The differential kinetics of SARS-CoV-2 infection elicited IgG response is notable, as it might complicate estimates of SARS-CoV-2 seroprevalence in vaccinated populations. Nevertheless, this phenomenon requires further investigations to inform future serosurveillance efforts.

Higher seroprevalence than that which was observed in rounds 20 and 21 of a seroprevalence survey conducted across the U.S. was observed. This is primarily because that survey used a dissimilar nucleocapsid assay, did not evaluate anti-S IgGs, and utilized a relatively small pediatric population with different demographics.

In rounds 20 and 21 of the aforementioned nationwide survey, the estimated seroprevalence was 13.4% and 17.5%, respectively. However, the findings of round 25 showed a seroprevalence of 40.1%, which was much more comparable to the current study results.

Based on positive molecular amplification testing, seropositive case ascertainment was 16%, and SARS-CoV-2 prevalence was 6.5%, thus indicating an underestimation of COVID-19 cases by 84% in Colorado children. To generalize these unadjusted results to the wider Colorado pediatric population, statewide confirmed case counts would require a multiplication factor of six, which would more accurately reflect the incidence of SARS-CoV-2 infections among Colorado children.

Nevertheless, these results provide an opportunity to improve awareness about SARS-CoV-2 infection and adopt mitigation measures like mandatory quarantine periods. These results could also help verify SARS-CoV-2 incidence estimates based on hospitalization levels at a mass scale.

Substantial variations in seroprevalence and seropositive case ascertainment were observed in different racial and ethnic groups. Accordingly, seroprevalence was much higher in Hispanic and non-Hispanic Black children, while it was lower among non-Hispanic White children.

Similar disparities were observed in lower seropositive case ascertainment among Black children as compared to non-Hispanic White children, thereby indicating reduced COVID-19 testing rates in the former ethnic minority groups. Importantly, relying solely on reported COVID-19 case counts of Colorado children would lead to the false assumption that SARS-CoV-2 infections were highest among White children. Complementing surveillance mechanisms like wastewater testing could help alleviate some reporting biases.

Despite the stringent implementation of SARS-CoV-2 mitigation measures in all schools of Colorado during the survey duration, the study findings showed higher SARS-CoV-2 prevalence among children. These observations also raise concern as to whether children are as susceptible to contracting SARS-CoV-2 infection as adults. If yes, these findings could inform future public health recommendations.

Another area that requires attention is regular screening and post-exposure testing among children, for whom COVID-19 is often asymptomatic or mildly symptomatic. The implementation of these approaches could improve case ascertainment and provide more information about disease prevalence in pediatric populations, which could help guide recommendations for respiratory viral infections with similar symptoms in children that might arise in the future.

Conclusions

The survey results provided evidence of previous SARS-CoV-2 infections in over one-third of Colorado children before the Delta variant peak; however, confirmed case counts were much lower in the study population. Thus, this survey should be repeated for data obtained after the Delta and Omicron variant peaks.

Similar to adults, the pediatric population was associated with racial and ethnic disparities. To this end, SARS-CoV-2 seroprevalence was higher, whereas viral testing rates and seropositive case ascertainment were lower in Hispanic and non-Hispanic Black children than non-Hispanic White children. Thus, there is an urgent need to address these racial/ethnic disparities in children and ensure equitable access to viral testing.