COVID-19 is 6-Fold More Prevalent than Reported Incidents, German Study Says

Family in Pandemic_Compressed

A seroprevalance study of 15,591 children in Bavaria, published October 28th in Med, revealed a six-fold greater prevalence of the SARS-CoV-2 virus than reported cases. More than half of those children (aged 1 to 18 years) were asymptomatic, underscoring the value of wide-spread population screenings for pandemic monitoring.

In reaching these conclusions, researchers at Germany’s Helmholtz Zentrum München research institute, led by Prof. Anette-G. Ziegler, developed a novel approach to measuring antibodies against SARS-CoV-2.

Specifically, the team defined antibody positivity as a dual-positive response against both the receptor binding domain and nucleocapsid proteins of the virus. This two-step approach produced test results with 100% specificity and greater than 95% sensitivity and overcomes the challenge of false positives that plagues many current antibody screening methods.

When the pandemic struck, the Ziegler team already was investigating the prevalence of Type 1 diabetes autoantibodies, an early marker for pre-symptomatic type 1 diabetes, among children in Bavaria. The study assayed capillary blood from 11,884 children and dried blood spots from 1,916 neonates. Adding a SARS-CoV-2 assay to the Fr1da clinical trial was quick and easy.

Because the Fr1da study was underway in 2019, the researchers were able to compare pre- and post-COVID-19 assays. None of clinical samples taken from children in 2019 were positive for SARS-CoV-2. Sensitivity was confirmed by assaying 75 individuals confirmed to have COVID-19. Of those, 73 tested positive (97.3% sensitivity). The researchers found no association between SARS-CoV-2 antibodies and Type I diabetes autoimmunity.

Between January and March 2020, as the pandemic was beginning, “antibody surveillance…resulted in frequencies of 0.08%,” the study reported. As the pandemic progressed, positive antibody tests increased. Antibody prevalence from April (0.61%) was six-fold higher than the incidence of authority-reported cases.”

Positive SARS-CoV-2 antibody tests climbed to 0.74% in May, 1.13% in June and dipped to 0.91% in July. Results for subsequent months were not included in the study.

Zielger and colleagues found notable variations in positivity among the seven regions of Bavaria, but no variations by age or gender. However, “Transmission in children with virus-positive family members was 35%,” the paper reported. Therefore, family members who had COVID-19 appear to have transferred the virus to children at a much higher rate than researchers expected.

In the U.S., the Centers for Disease Control and Prevention (CDC) began tracking seroprevalance last summer. The most current data (for the first two weeks of August) ranges from a low of 0.4% in Alaska to a high of 22.5% in New York. Most states were around or below 5%, based on tests from blood samples provided by commercial labs. In New York, 26% of the population under age 18 had SARS-CoV-2 antibodies in their bloodstreams.

Population seroprevalance surveys have significant implications on public policy and health.

“Our study… revealed the discrepancy between reported virus positive cases and antibody prevalence,” Markus Hippich, who conducted the study as first-author and postdoc at Helmholtz Zentrum München, said in a statement.

Because many individuals, and nearly half of children, exhibit no symptoms of COVID-19, they never are tested. Therefore, viral testing alone is not a reliable indication of a population’s actual virus exposure.

Ziegler advocated for national screening programs to furnish that information. As she said in a statement, “National antibody screening programs with high specificity and sensitivity could provide countries reliable data to prepare for the future, help them contain the virus spread and monitor the impact of their regional and national containment policies.”

The government of Canada agrees. It recently announced it is providing $1.9 million to assess SARS-Cov-2 seroprevalence nationwide. The Canadian Partnership for Tomorrow’s Health (CanPath) will focus on high-risk populations and will follow 20,000 participants who may have been exposed to the virus and who are unlikely to be involved in other research. This means residents of long-term care homes and those in rural or underserved urban communities with high incidence rates of COVID-19.  

Combining viral testing with antibody-screening approaches delivers a more accurate picture of a population’s rate of exposure to SARS-CoV-2 (or any other virus). However, with antibody screening results can only provide a snapshot of the infection rate as it was two to four weeks ago. That’s because antibodies take between two and four weeks to appear after viral infections, Ziegler noted.

The presence of SARS-CoV-2 antibodies in the bloodstream may or may not confer immunity. Recent evidence suggests any immunity that exists may not be durable. But, if antibodies to SARS-CoV-2 do confer immunity, understanding the extent of a population’s immunity could have significant public policy and health consequences.

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