COVID Infection Before Vaccination May Weaken Some T Cells: Study

Marcia Frellick

March 23, 2023

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

A key player in the body's ability to attack COVID-19 is weakened among people who were infected before getting their first two shots of mRNA vaccine, new research suggests.

But even though the key cells (CD8+ T cells) were found to have also been weakened in people who were not vaccinated and contracted COVID-19, the researchers stress that vaccination still boosts defense, the authors say in a press release.

Those who got their shots after infection were still better protected than unvaccinated people who had contracted COVID-19, they write.

Chuck Hackett, PhD, deputy director of the Division of Allergy, Immunology and Transplantation at the National Institutes of Health in Bethesda, Maryland, told Medscape Medical News it's important to note in this research that the CD8+ cells are only one part of the body's immune response, even though they are important to killing cells infected with SARS-CoV-2.,

CD4+ T cells help produce the antibodies to fight off SARS-CoV-2 infection and are thought to be more important in protection, he said, and they were increased in people who were infected before vaccination.

"The CD4s are there, and they've been boosted by the vaccine even if you've been infected first," said Hackett, who was not on the research team.

This study shouldn't scare people who were infected before they had the vaccine into thinking they are not protected from future infection, he said, emphasizing that "you will definitely have protection."

Findings of the study, led by Mark M. Davis, PhD, director of the Stanford Institute for Immunity, Transplantation and Infection, were published online March 15 in the journal Immunity. Davis is a professor of microbiology and immunology at Stanford University School of Medicine in Palo Alto, California.


    New Tool Opens a Window

    Davis and colleagues designed a highly sensitive tool – using what's known as spheromer technology — to study how CD4 and CD8 T cells respond to SARS-CoV-2 infection and vaccination.

    "The beauty of the study, from my perspective, is that until they developed these particular reagents, the spheromers, which can detect individual, antigen-specific CD8 cells, we didn't know [how the cells responded differently]. It gives us a way, now, of tracking responses," Hackett said,

    He said the ability to track these immune responses may become important in developing future vaccines.

    So, the real breakthough in this study, Hackett said, is the way the researchers were able to focus in on some of the specifics of how the immune system attacked the virus.

    Davis' team studied blood samples of 351 people in three groups:

    • Never infected and received two doses of the Pfizer-BioNTech vaccine

    • Had been infected with SARS-CoV-2 and were vaccinated

    • Had COVID-19 and were unvaccinated

    What We Knew Before

    The results of this study come after two major studies that compared the immunity from getting infected and immunity from vaccination.

    Medscape reported in February on a study in The Lancet that said the natural immunity provided by a COVID infection protects a person against severe illness similar to two doses of mRNA vaccine.

    However, that article points out that gaining immunity through infection is far riskier than vaccination.

    Medscape reported in January on another study, also in The Lancet, involving the combination of both having the vaccination and being infected — those with "hybrid immunity" — are better protected than those who were infected but not vaccinated.

    Many Unanswered Questions

    Gregory Poland, MD, founder of the Vaccine Research Group at Mayo Clinic in Rochester, Minnesota, told Medscape Medical News that even though this new study raises concern, it's important to remember the study was done in a relatively small number of people, with one kind of mRNA vaccine, and with data gathered in the early wave of COVID. Thus, it's unclear whether the hypothesis would be generalizable to larger populations now.

    "Everybody rushes to overinterpret the meaning of this," he said.

    It brings to light new information about COVID and deserves to be repeated to determine whether there is clinical significance of the findings, Poland added.

    "We need to understand whether this isolated laboratory finding has any clinical consequence," he said. "You can't tell that by this study."

    Hackett adds that another limitation of this study is that this research studied only blood samples — and T cells are also found in tissues, such as in the nose and lungs.

    "Usually what's in the blood is representative of what's in the tissues. But it is possible that in the tissues there are good CD8 cells that haven't been affected this way," Hackett said.

    The study was co-funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the Howard Hughes Medical Institute. Additional support was provided by the Bill and Melinda Gates Foundation, the Sean N. Parker Center, and the Sunshine Foundation.

    Co-author Vamsee Mallajoysula and senior author Mark Davis are inventors on a patent application on the spheromer technology described in this work. The other authors report no relevant financial relationships.

    Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, and, and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick


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