Almost 17 Million Undiagnosed Cases Added to Early COVID-19 Tally

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Multiply by five the number of reported cases of SARS-CoV-2 infections early in the pandemic, National Institutes of Health (NIH) researchers suggest, if you want to get closer to the true number of Americans who were infected.

For each infected person reported up until mid-July 2020, another 4.8 Americans went undiagnosed, many with either mild or no symptoms, the study shows. This translates to an additional 16.8 million infections on top of the official 4.8 million reported cases.

"During respiratory viral outbreaks and pandemics, the identified cases often represent only a small subset of what is really happening in a community," lead author Matthew J. Memoli, MD, told Medscape Medical News.

Memoli and colleagues looked at antibodies to SARS-CoV-2 using dried blood samples from 8058 people. Participants had not been diagnosed with COVID-19. Each person completed the Behavioral Risk Factor Surveillance System survey to help researchers study a nationally representative sample.

Studying seropositivity "allows us to gain a better understanding of how quickly the virus was able to spread and better estimate how long it was likely in the US before fully recognized," added Memoli, director of the Clinical Studies Unit, Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases at the NIH.

The study was published online June 22 in Science Translational Medicine.

"It is useful to understand how much circulating virus there was early on," George Rutherford, III, MD, professor of epidemiology & biostatistics
director, Prevention and Public Health Group at the University of California San Francisco, told Medscape Medical News.

"This kind of sleuthing to try to understand how the virus got into the United States...could help for next time," added Rutherford, who was not affiliated with the study.

Rates Higher in Women, African Americans

Memoli and colleagues were able to estimate differences by geography, age, sex, and race. For example, the Northeast and mid-Atlantic US had the highest seropositivity rates versus the Midwest, where rates were lowest. At the time blood samples were collected, urban area seropositivity rates were 5.3% versus 1.1% for rural areas.

Furthermore, women had a higher seropositive estimate rate, at 5.5%, versus 3.5% for men. Also, African Americans had the highest seroprevalence estimate at 14.2%, followed by 11.1% for other/unlisted race participants, 6.8% for American Indian/Alaska Native, and 2.5% for White/Caucasian individuals. Asians had the lowest seroprevalence estimate in the study, at 2.0%.

Lessons Learned

Rutherford said it would be useful to continuously monitor blood donors around the United States to gain earlier insight for any future pandemic.

In addition to being better prepared next time, Memoli said their findings can foster more accurate COVID-19 infection and mortality rates. This kind of information "can help us to evaluate the various measures taken to reduce the impact of the pandemic."

The under-reporting of cases early in a pandemic can be partly explained by a lack of initial high-quality testing, clear case definitions, and high clinical suspicion, Memoli said.

The current report is part of a full year effort by the NIH to monitor the evolution of SARS-CoV-2 immunity in the United States. Together, the two parts of the study "will allow us to further understand this pandemic and how immunity developed in our country both before and after vaccine was available," Memoli said.

Sci Transl Med. Published online June 22, 2021. Full text

Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology, and critical care. Follow Damian on Twitter: @MedReporter.

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