Antibodies to SARS-CoV-2, the virus that causes COVID-19, were present in the blood of 96.4% of Americans over the age of 16 by September 2022. This is according to a serological survey – an analysis testing the presence of these immune defense molecules – carried out on samples from blood donors.
A serological survey like this helps researchers estimate how many people have been exposed to any part of the coronavirus, whether through vaccination or infection. Both can trigger the generation of antibodies against SARS-CoV-2. And by identifying the type of antibody someone has in their blood, researchers can break down the 96.4% into different types of immunity: infection-derived, vaccine-derived, and hybrid.
The COVID-19 vaccines used in the United States are based on a single part of the virus – the spike protein, or S. Researchers can tell that a person has been vaccinated and not infected if their blood only contains anti-S antibodies that target this spike protein. If someone has anti-N antibodies, which target the virus’s nucleocapsid protein, that’s a sign they’ve been infected with SARS-CoV-2. To reliably identify someone with hybrid immunity, a researcher would need to match someone who has anti-N antibodies to an official vaccination database.
What about the 3.6% without antibodies?
Immunologists know that antibody levels decline in the following months a COVID-19 infection or vaccination, and this is true for many pathogens. Some people may have had antibodies at some point, but they are no longer detectable. And not all infections lead to a detectable antibody response, particularly if the case was mild or asymptomatic.
Another factor is antibody test accuracy. No test is perfect, so a small percentage of people who do have antibodies may test negative.
Together, these considerations mean that the 96.4% number is likely an underestimate. It seems reasonable to conclude that almost no one in this population was infected with SARS-CoV-2 or received a COVID-19 vaccine.
A clearer picture of the spread of a virus
Serological surveys are useful for understanding the likelihood that different types of people – of different ages or races, for example – have been infected. For this purpose, a serological survey can be much more reliable than using data on people who have had a positive PCR test, or who report having had a positive rapid antigen test, because obtaining a positive test is strongly influenced by access to care, health care behavior and the severity of your illness. These are sources of so-called biases.
This bias has two effects: it leads to a strong underestimation of the proportion of the total population infected and it can lead to false differences between groups. For example, people with mild symptoms are less likely to get tested and are also likely to be younger. Researchers could draw the erroneous conclusion that because they don’t get tested, these people don’t actually catch the virus.
Considering antibodies as a marker of infection is not biased by such behavioral factors. Many serological surveys, including those that we worked in Chennai, IndiaAnd Salvador, Brazil, found similar or even higher seroprevalence in children compared to young adults, contradicting an old narrative that children were less susceptible to the virus. Instead, our results suggest that infections in children were less likely to be detected.
What does this stat mean for future waves?
Antibodies are not only a marker of previous infection; part of their job is to help prevent future infection with the same pathogen. Thus, serological surveys can be used to understand immunity levels in the population.
For some diseases, like measles, immunity is essentially lifelong and having antibodies means you are protected. However, for SARS-CoV-2, this is not the case, as the virus has continually evolved new variants capable of re-infecting people despite their antibodies.
Nevertheless, many studies have shown than individuals with hybrid immunity will be more protected against future infection and its variants than those who only have immunity derived from vaccine or infection. It may be useful to know the proportion of the population with single-source immunity in order to target certain groups with vaccination campaigns.
Matt Hitches is assistant professor of biostatistics, University of Florida And Derek Cummings is Professor of Biology, Emerging Pathogens Institute, University of Florida.
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