Two NIH-supported studies have found evidence of millions of undiagnosed cases of COVID-19 — some cases dating as far back as December 2019 — indicating that the SARS-CoV-2 virus was more widespread at an earlier date than previously thought.

Two NIH-supported studies have found evidence of millions of undiagnosed cases of COVID-19 — some cases dating as far back as December 2019 — indicating that the SARS-CoV-2 virus was more widespread at an earlier date than previously thought.

What you need to know

Two studies supported by NIH looked at the early spread of COVID-19 in the United States. One study found cases dating back to as early as December 2019. The other concluded that asymptomatic cases of COVID-19 are far more common than previously reported, which suggests that the SARS-CoV-2 virus — which causes COVID-19 — has greater reach and infectious potential than originally thought.

What did the researchers do?

In one study, researchers collected blood samples from 8,058 people across the United States in the spring and summer of 2020. Participants also answered questions about where they live, their age and other demographic information, their lifestyle, and their health. None of the participants had been diagnosed with COVID-19.

The researchers tested the blood samples and found that 304 (4.6%) of the blood samples were seropositive, meaning they contained antibodies against the SARS-CoV-2 virus. These antibodies can be created only after COVID-19 infection or vaccination. Using this data, researchers estimated that for every COVID-19 diagnosis during the spring and summer of 2020, 4.8 other active COVID-19 cases went undiagnosed. By July of 2020, nearly 17 million people may have had COVID-19 and not known it.

The study was a collaboration between researchers at the National Cancer Institute’s Frederick National Laboratory for Cancer Research, the National Institute of Biomedical Imaging and Bioengineering, the National Institute of Allergy and Infectious Diseases, and the National Center for Advancing Translational Sciences.

In a separate study, scientists with NIH’s All of Us Research Program tested 24,079 blood samples that program participants had contributed between January and March 2020. Of these participants, nine people in five U.S. states had antibodies against SARS-CoV-2. Most of the positive samples were collected before the first cases of COVID-19 had been reported in those states. Because antibodies do not develop for at least two weeks after SARS-CoV-2 exposure, the participants must have come into contact with the virus several weeks before they gave their samples. This suggests that SARS-CoV-2 was spreading through the United States earlier than previously realized. Additional research from the American Red Cross and the Centers for Disease Control and Prevention came to similar conclusions.

Why is this research important?

These studies suggest that SARS-CoV-2 arrived in the United States earlier than previously thought and that the virus spread even faster and more thoroughly than we realized. The implementation of public health measures such as increased testing and vaccine and mask mandates helped to slow that spread, and these findings underline the importance of such measures in future battles against SARS-CoV-2 variants and other diseases.

Where can I go to learn more?

NIH study offers new evidence of early SARS-CoV-2 infections in U.S.

  • NIH summarizes the findings of the antibody study from the All of Us Research Program.

NIH study suggests COVID-19 prevalence far exceeded early pandemic cases

  • NIH outlines its findings on the early prevalence of COVID-19 in the United States.

Antibody Testing for COVID-19 Research

  • The All of Us Research program explains its COVID-19 antibody study and the results.

Study Suggests Possible New COVID-19 Timeline in the U.S.

  • The American Red Cross reports on its findings of early COVID-19 cases in the United States.

Sources

Althoff, K. N., Schlueter, D. J., Anton-Culver, H., Cherry, J., Denny, J. C., Thomsen, I., Karlson, E. W., Havers, F. P., Cicek, M. S., Thibodeau, S. N., Pinto, L. A., Lowy, D., Malin, B. A., Ohno-Machado, L., Williams, C., Goldstein, D., Kouame, A., Ramirez, A., Roman, A., ... Schully, S. D., on behalf of the All of Us Research Program. (2021). Antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in All of Us Research Program participants. Clinical Infectious Diseases, ciab519. https://doi.org/10.1093/cid/ciab519

Basavaraju, S. V., Patton, M. E., Grimm, K., Rasheed, M. A. U., Lester, S., Mills, L., Stumpf, M., Freeman, B., Tamin, A., Harcourt, J., Schiffer, J., Semenova, V., Li, H., Alston, B., Ategbole, M., Bolcen, S., Boulay, D., Browning, P., Cronin, L., David, E., … Stramer, S. L. (2021). Serologic testing of US blood donations to identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–reactive antibodies: December 2019–January 2020. Clinical Infectious Diseases, 72(12), e1004–e1009. https://doi.org/10.1093/cid/ciaa1785

Kalish, H., Klumpp-Thomas, C., Hunsberger, S., Baus, H. A., Fay, M. P., Siripong, N., Wang, J., Hicks, J., Mehalko, J., Travers, J., Drew, M., Pauly, K., Spathies, J., Ngo, T., Adusei, K. M., Karkanitsa, M., Croker, J. A., Li, Y., Graubard, B. I., ... Sadtler, K. (2021). Undiagnosed SARS-CoV-2 seropositivity during the first 6 months of the COVID-19 pandemic in the United States. Science Translational Medicine, 13(601), eabh3826. https://doi.org/10.1126/scitranslmed.abh3826

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Page last updated: January 5, 2022