People infected with the coronavirus before getting their first two COVID-19 shots may still be at risk of potentially getting reinfected — and there’s a reason why, according to a new study. Prior research suggested that hybrid immunity, meaning COVID-19 vaccination and infection, may provide the best protection against reinfection regardless of the order, according to a review of the study published in January involving researchers from Canada. The current study published in the peer-reviewed medical journal Immunity on March 15, however, suggests the order possibly does matter.
In studying blood samples of people who received two doses of Pfizer’s COVID-19 vaccine and unvaccinated individuals who caught the virus, researchers discovered those vaccinated without having been infected with the virus were the most protected against COVID-19, according to a National Institutes of Health March 20 news release on the findings.
Ultimately, those who were vaccinated following infection were still better protected than unvaccinated people who had COVID-19 previously, according to the study. The work received funding from the Howard Hughes Medical Institute, the National Institute of Allergy and Infectious Diseases, the Bill and Melinda Gates Foundation, the Center for Human Systems Immunology, the Sean N Parker Center, and the Sunshine Foundation.
The reason why vaccinated individuals without a prior COVID-19 infection were the most protected is that prior infection damages a “key” cell’s immune response to the vaccine, the study suggests. Specifically, the study found COVID-19 infection weakens the response of the CD8+ T cell, which can help kill cells infected with a virus.
“The apparent damage of the CD8+ T cell response by viral infection is cause for concern, and may leave even vaccinated individuals with a prior infection at risk for subsequent infections or other health issues,” study authors wrote.
The authors also wrote it’s “important to note” their findings are contrary to research published in the New England Journal of Medicine in July 2022. This study found that vaccination “enhanced protection” against symptomatic omicron BA.2 infections in people who previously had COVID-19.
MORE ON THE CURRENT COVID-19 STUDY
The study led by Dr. Mark M. Davis, the director of the Stanford Institute for Immunity, Transplantation, and Infection, assessed how immune cells, specifically CD4+ T cells, and CD8+ T cells, reacted to both COVID-19 infection and vaccination, the release said. Both of these cells work together and respond to COVID-19 by destroying infected cells to help stop a person from becoming infected with the virus, according to the NIH.
Among the group of people who received two doses of the Pfizer vaccine without a prior COVID-19 infection, vaccination triggered strong responses of CD4+ T cells and CD8+ T cells to the SARS-CoV-2 spike protein, the study found.
The Pfizer vaccine, which is an mRNA vaccine, includes pieces of the SARS-CoV-2 spike protein to trigger an immune response without causing a person to get sick with COVID-19. Meanwhile, people infected before getting two Pfizer shots produced fewer CD8+ T cells targeting the virus’ spike protein, according to the research. The cells also had “less functionality,” the release said.
Overall, unvaccinated people who caught COVID-19 had even lower levels of these CD8+ T cells, according to the study. “The new findings highlight the need to develop vaccination strategies to specifically boost antiviral CD8+ T cell responses in people previously infected with SARS-CoV-2,” the release said. The study has a few limitations, including how it’s possible that a similar analysis could lead to different results, the researchers wrote. They said that “future studies are warranted.”