An NIEHS-led study suggests that the majority of North Carolinians have some level of immunity against SARS-CoV-2, which is the virus that causes COVID-19. The study, which was conducted in a subset of the population, also found that vaccination was superior to natural infection in terms of generating antibodies that protect against the disease.

Garantziotis said another finding of the study was that people who were not vaccinated were also less likely to follow social distancing or other mitigation strategies. (Photo courtesy of Steve McCaw)

Stavros Garantziotis, M.D., medical director of the NIEHS Clinical Research Unit, presented the new research in an online seminar Aug. 30. He noted that even though the virus and the public health response to it continue to evolve, current signs indicate that the pandemic has entered a more manageable phase.

“We are in a better spot today compared to two years ago or even one year ago,” said Garantziotis. On the human side of the equation, he noted, there is more immunity, more medications, and more experience to combat COVID-19. On the virus side, Garantziotis said, SARS-CoV-2 is evolving to behave more like other human coronaviruses, which typically cause only minor illness.

The new findings, which will be published in an upcoming issue of the journal Microbiology Spectrum, are consistent with evidence from other studies showing the widespread prevalence of antibodies against SARS-CoV-2.

Rapid response

NIEHS launched the COVID-19 Serological Surveillance Study in January 2020 to gain a rapid understanding of exposures and immunity to SARS-CoV-2 as it moved throughout the population.  According to Garantziotis, gathering this knowledge could greatly impact the response to current and future pandemics.

The team collected blood samples from more than 629 study volunteers and tested their serum using two different types of antibody tests. One test detects antibodies against a viral protein called nucleocapsid, which is hidden within the coronavirus and only becomes visible to the body after the virus has infected cells. If a person produces anti-nucleocapsid antibodies, that means they have experienced a prior SARS-CoV-2 infection.

The other test detects antibodies against the coronavirus spike protein, which is present on the surface of the virus and in vaccine formulations. Those antibodies indicate a person has been vaccinated or has experienced a prior infection. By using both tests, the researchers could differentiate between whether a person developed immunity because of infection or vaccination.

Vaccination is best

The study found that vaccination led to robust antibody responses, even higher than those generated by infection.

“This was a discussion that was raging a year ago,” said Garantziotis. “At least with this study, it shows that if you’re vaccinated but not infected, your antibody response starts stronger and lasts longer compared to somebody who was infected but not vaccinated.”

The antibody responses from vaccination were further increased by subsequent encounters with viral material, either through a booster or an infection.

“Boosters boost: they do what they are supposed to do,” said Garantziotis. “The body now pays more attention. The decline in antibody levels is less visible or not as pronounced as with the original vaccine.”

However, not all booster responses are created equal. The findings showed that men had a substantially lower response to boosters than women.

“It is a fact of life that women have a higher immune response than men,” Garantziotis said. “It is also well known that men die from COVID-19 more often than women.”

Omicron changed everything

With the emergence of the Omicron variant of SARS-CoV-2, the researchers noticed a dramatic change in the antibody profiles captured in their study. Garantziotis presented data that has not yet been submitted for publication suggesting that it is no longer possible to predict whether a person will become infected based on their antibody levels.

“The antibodies have lost some of their ability to protect against infection,” said Garantziotis. “But let me be absolutely clear: there is still protection against severe disease.”

(Marla Broadfoot, Ph.D., is a contract writer for the NIEHS Office of Communications and Public Liaison.)