Study finds US pediatric COVID-19 cases are higher than expected

Since the onset of the pandemic, seroprevalence studies of coronavirus disease 2019 (COVID-19) have been used to identify population immunity, transmission rates, risk factors and response of ‘immune’ individuals to variants of concern. In general, these studies involve collecting serum from individuals, recording evidence of previous COVID-19 infection/vaccination, and then examining the response of the sera using commercially available tests for antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins.

Study: Methods for Estimating SARS-CoV-2 Seroprevalence and Reported COVID-19 Cases in U.S. Children, August 2020 – May 2021. Image Credit: L Julia/Shutterstock

Normally, these tests are against the nucleocapsid (N) antibodies or antibodies that bind to the receptor binding domain (RBD) of the S1 subunit of the spike protein. The spike protein is integral to the pathogenesis of SARS-CoV-2 – the RBD binds to angiotensin converting enzyme 2 (ACE2) to allow viral entry and the N-terminal domain of the S2 subunit is responsible for membrane fusion.

Most of these studies are taking place in adults, but as schools reopen there is great concern about the spread of worrisome variants such as the Delta variant through children. Researchers at the Centers for Disease Control and Prevention (CDC) examined differences in seroprevalence between pediatric age groups to estimate an infection-to-case ratio. This could allow for further exploration of trends in the transmission of COVID-19 in children.

A preprinted version of the study is available on the medRxiv* server while the article is undergoing peer review.

The study

The researchers collaborated with three labs to test random samples of sera submitted for routine clinical testing using commercially available assays – three assays were used, two targeting the N protein and one targeting the S protein. These were used between August 2020 and January 2021. Between February and May 2021, the samples were tested for Ig or IgG anti-N antibodies. Weighted estimates of seropositivity were calculated for each state and month, taking into account differences in age, gender and urban/rural residence.

Using a post-stratification process known as raking and layered bootstrapping, the scientists were able to explain the differences between the tests used. The mean monthly seroprevalence estimates were multiplied by population by age in each state and each month to calculate the cumulative infections for each age group. The date of illness was determined by the first onset of symptoms, the earliest recorded date, or the date reported to the CDC. Data from 14 states, as included in the analysis, from various geographic locations within the US

More than 67,000 serum specimens from children were tested between August 2020 and May 2021. After January 2021, serum specimens from eight states were tested for anti-N antibodies using pan-Ig assays, and another six states were tested for IgG-specific antibodies. in the researchers’ analysis.

The results showed that the number of SARS-CoV-2 infections was slightly higher in estimates across the board, with a wide range of ratios for different states; New Jersey showed 58.2, Connecticut showed 0.8. The infection:case ratio was highest from August to October 2020 and remained stable until May 2021. Overall, the pan-Ig-anti-N assays showed higher spreads of infection:case ratios than the IgG-specific immunoassays .

The authors conclude that although the seroprevalence of anti-SARS-CoV-2 antibodies is higher than expected in children, the vast majority of children as of May 2021 show no evidence of previous infection by the disease. While this may come as a relief to parents, these results may not last long.

For the vast majority of this time, many states imposed restrictions on movement, contacts, and social distancing to curb the spread of the disease, and attempted to curb class size or close schools altogether. With many of these restrictions lifted and schools reopening, the disease could be growing faster than before.

*Important announcement

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, should guide clinical practice/health-related behavior or be treated as established information.

Reference magazine:

Couture, A. et al. (2021) “Methods for the estimation of SARS-CoV-2 seroprevalence and reported COVID-19 cases in US children, August 2020 – May 2021”. medRxiv. doi: 10.1101/2021.09.26.21263756.

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