How many people out there have been exposed to SARS-CoV-2? It’s a tricky question, once you think about all the people who have experienced COVID-19 symptoms over the last several months, but didn’t go to the hospital. And there’s a murkier penumbra of people who may have fended off the virus with a minor immune skirmish.

A recent Emerging Infectious Diseases paper from Emory investigators includes antibody tests on a group of more than 100 adults in the Atlanta area who experienced mild flu-like symptoms this spring, but couldn’t get tested for SARS-CoV-2 itself.

A sizable fraction (22 to 48 percent, depending on when they provided blood samples) had elevated levels of IgM against the coronavirus. IgM is the “rookie” antibody produced when the immune system is first encountering something, as opposed to the more seasoned IgG, which appears later in an immune response and tended to rise only in people who were hospitalized. The Emory authors came to a conclusion that others are also reaching:

“Examining IgM and IgG against multiple SARS-CoV-2–related antigens may thus better inform natural history and vaccine studies than any one antibody.”

To answer these kinds of questions more comprehensively, investigators will need to go broader. For example, this week the American Red Cross published data on what proportion of its blood donors have antibodies against SARS-CoV-2. About 3 percent of first-time donors did, using their criteria.

For big answers, we can look to studies such as Emory’s COVID-Vu, a nationwide population-based study using antibody and virus tests taken at home. Rollins School of Public Health researchers received a $6.6 million grant to launch the study this summer. This type of study is designed to cover everyone, whether they were sick or not.

One of the lead investigators, Aaron Siegler, told Lab Land his team has mailed out about 15,000 test kits and is beginning to get responses back (recipients sometimes call their local TV stations too). Once they’ve gauged how response rates vary geographically and among different demographic groups, they can adjust so that the study looks at the population proportionally.

“We’ll be able to analyze the test findings by critical variables such as people’s symptoms, where they live, sociodemographic factors including race/ethnicity, and underlying conditions – among many key factors,” Siegler said.

COVID-Vu will be able to return research test results to individual study participants. While the COVID-Vu team also plans to post interim aggregate results as they are analyzed, no individual’s test results will be disclosed publicly. The protocol combines measurements in a two-step procedure to reduce false positives, Siegler said.