Who Has Had COVID-19: An Immunologic Survey

How many of us have had COVID-19 or received vaccinations? The numbers of those inoculated are a bit easier to come by, but to count all those infected we’d have to test everybody. (That hasn’t happened – and won’t be happening.) Knowing the number of asymptomatic transmitters is helpful in both understanding who’s most impacted by COVID-19 and achieving the nirvana of herd immunity. A new study looks at a different population among us: blood donors.

Why blood donors?

Two reasons immediately come to mind; they are generally healthy so that we may get a better idea of the asymptomatic. They donate blood that can be tested for antibodies without all the rigmarole of consent and time involved in coming in getting stuck. The study involved blood donors, age 16 or greater, and specimens collected between July 2020 and May 2021. Samples were collected nationally, adjusting for our varying demographies, each region contributing 500 to 4,000 samples monthly. Those individuals known to have had COVID-19 were excluded to remove the effect of convalescent plasma. 

Specimens were tested for COVID-19 antibodies; the two mRNA vaccines produce a response against the S1 portion of the spike, infection-acquired immunity produces antibodies against both the S1 and N terminal portion of the spike—this helps us identify those who have experienced COVID asymptomatically. 

The findings are based upon 1,443,519 samples from blood donors who were 

  • Primarily non-Hispanic white, 85%
  • Age 50 to 64, 36.5%
  • Donors below the age of 29 and Hispanics, non-Hispanic Asians, and non-Hispanic Blacks were under-represented. 

You can see from this graphic the regional spread of COVID seropositivity over time. 

While the Northeast garnered all the headlines early in the pandemic, it quickly spread. Despite the current headlines, seroprevalence was low in the South in May of this year. More instructive is the seroprevalence nationally.

Seropositivity from infections remains relatively constant, but vaccination acquired seropositivity increases dramatically – suppressing the parallel rise we might have expected in infection-induced seropositivity. The researchers estimate that nearly half of the US population in May had COVID-19-directed antibodies. 

More telling are these series of graphs, all with the basic shape seen to the left but broken down by region, ethnicity, gender, and age. 


  • Men and women had essentially the same infection-acquired immunity, but women edged men out when getting vaccinated. 
  • It is no surprise that the oldsters, over 65, had the least infection-acquired immunity, most likely due to the high mortality and weakened immune response that makes them vulnerable. They also had the wisdom to get vaccinated. Not feeling the call of their mortality, the younger amongst us had fewer vaccinations and more asymptomatic infections. Perhaps the Delta variant is changing their perspective.
  • The ethnic and regional differences are consistent with reporting, more asymptomatic among Hispanics, Asians, and Black, with fewer vaccinations. And very similar regional responses, although the leaders change over time. The asymptomatic infections in the Midwest and South are consistent with the current headlines of overcrowding. Remember, the asymptomatic share the virus with others, who may not be as asymptomatic. They also seem a bit slower to recognize the value of vaccination. 

There are a lot of asymptomatic individuals resulting in an underreporting of the true incidence of COVID-19. From a public health perspective, the asymptomatic transmission of COVID-19 drives the mandates for masks and social distancing in the absence of vaccination. You can disagree about the “need” for these measures, but can we at least agree on the data?

9/11 is fast approaching, and it has me thinking, as I am sure it does for all of us who were old enough to experience that national moment. I was profoundly affected by the deaths of nearly 3,000 of my fellow citizens. I am sure you were too. Why has the death of almost 648,000 from COVID-19 not galvanized our national spirit in the same way and proven so divisive?


Source: Estimated US Infection- and Vaccine-Induced SARS-CoV-2 Seroprevalence Based on Blood Donations, July 2020-May 2021 JAMA DOI: 10.1001/jama.2021.15161