Scientists at the National Institutes of Health who studied blood samples from across the United States have discovered that for every coronavirus infection recorded during the spring and summer of 2020, nearly five more went undetected — amounting to nearly 17 million additional cases by July 2020.
The discovery, published this week in the journal Science Translational Medicine, reveals that the coronavirus was far more widespread in the early months of the COVID-19 pandemic than previously thought, and could help scientists and health officials better respond to future outbreaks.
At the beginning of the pandemic, experts realized many infections were slipping under the radar. But without the means to implement a comprehensive testing program, the extent of the undercount was unknown, said Dr. Ellen Foxman, an immunologist at Yale University.
“That was the big question: For each infection that we actually do diagnose, how many are we not diagnosing?” said Foxman, who was not involved in the new research.
Many studies attempted to tackle this question in various ways. “But the problem is a lot of them had a very specific, small population that was being looked at,” she said — a cruise ship, say, or a shelter.
A team of immunologists, engineers, clinicians and statisticians across the NIH worked together to try and get a better handle on the number of undiagnosed coronavirus infections by looking for antibodies in blood samples. If antibodies to SARS-CoV-2 were present, it would be an irrefutable sign that the person’s immune system had encountered the virus.
Some of the researchers fine-tuned a mail-in test kit system that allowed participants to collect their own blood at home instead of having to visit a clinic for a blood draw. Volunteers used a lancet to prick their fingertip and squeeze out droplets of blood that they deposited into sampling devices. The dried blood spots could then be mailed to the NIH, where the samples were screened for antibodies.
This user-friendly mail-in format meant the scientists could gather samples from far and wide, said Kaitlyn Sadtler, an immunologist and bioengineer at the NIH’s National Institute of Biomedical Imaging and Bioengineering and one of the paper’s senior authors.
“We had samples from Alaska, we had samples from Hawaii,” Sadtler said. Basically, “if a delivery truck can make it to your house, we could get a sample from you.”
The scientists had planned to recruit about 10,000 participants. Thanks to publicity about the work, they ended up with more than 240,000 volunteers — far more than they could feasibly study. So they used the demographic and geographic information the volunteers provided to select a group that was representative of the county’s population based on the U.S. census.
The scientists sent out about 11,000 kits over late spring and summer and received just over 9,000 back, most of them between May 10 and July 31. About 1,000 had incomplete information, but the rest could be analyzed.
The results: By last summer, after the first wave of the pandemic, there were roughly 16.8 million undiagnosed coronavirus infections in addition to the roughly 3 million that were confirmed. The researchers calculated that for every infection that had been officially tallied, about 4.8 others were uncounted.