If I’ve Had COVID-19, Do I Still Need Two Doses of Vaccine?

While there are three safe and effective vaccines authorized in the U.S. to protect against COVID-19, there’s still a lot about vaccine immunity that researchers are still trying to figure out. One question has to do with the millions in the U.S. who have been infected with SARS-CoV-2 and recovered. Do they have natural immunity because of their infection, and if so, do they still need to get vaccinated? How much additional protection do the vaccines give them?

In a study published April 1 in Nature Medicine, researchers led by a team at Cedars-Sinai Medical Center report that people who recovered from COVID-19 generated the same level of antibodies against SARS-CoV-2 after one dose of the Pfizer-BioNTech vaccine as people who have never been infected and receive the recommended two doses of the shot.

The data will raise questions about why people who have recovered from COVID-19 need two doses, but the U.S. Centers for Disease Control continues to recommend that people receive two doses of shots from Pfizer-BioNTech and Moderna, which were designed and tested as doube-dose regimens. Getting both doses provides the optimum protection against disease, they say.

In some ways, the results aren’t surprising, since immunity generally works on a what scientists in the field call a “prime-boost model”: immune cells need to be primed, or exposed to a virus—in this case with a first dose of a vaccine—in order to later on recognize it as foreign and design the right antibodies and other defenses dedicated to blocking or destroying it. Once these forces are marshaled, a boost—a second dose—activates the system and puts the immune response into motion. Natural infection, some experts thought, might serve as an effective prime, and a dose of vaccine as a boost for adequate protection from COVID-19. And the latest data seem to support that theory.

The study included nearly 1,000 health care workers who were vaccinated at Cedars-Sinai; about half provided blood samples before they were vaccinated, and some continued to provide blood samples after their first and second doses of vaccine. Dr. Susan Cheng, director of the Institute for Research on Healthy Aging at Cedars-Sinai and a co-author of the study, says the team did not set out with any preconceived ideas about what they would find in this vaccinated group. “We knew there was going to be variation in responses to the vaccines, and we wanted to understand that heterogeneity,” she says. “We were ready for anything; we were going to take all the data and look to see if there were differences between younger versus older people, male versus female, or combinations of pre-existing conditions.”

Their study group included 78 people who had recovered from COVID-19, and it turned out they provided the most interesting data signal. “It popped out like a smoking gun that we couldn’t ignore,” says Cheng. Among this group, 35 provided blood samples after receiving their first dose of the Pfizer-BioNTech vaccine. When Cheng’s team tested them for antibodies to SARS-CoV-2 they found that the levels were similar to those among people who had never been infected but received two doses of the vaccine.

“If I were an otherwise younger, healthy person who recovered successfully from COVID-19, then I would feel fairly confident that one dose [of vaccine] is probably sufficient,” says Cheng.

That doesn’t necessarily mean that anyone who has had COVID-19 should skip the second dose of their vaccine if it’s recommended. “It’s about timing,” says Cheng. “If this pandemic lasts two years, and somebody had an infection two years ago, based on our data we can’t say whether they would be okay with one dose or two.” And for older people who might have been hospitalized for COVID-19 and recovered, their immune responses might not be as robust so they may need the second dose to bolster their protection.

The data also do not address the new variants of SARS-CoV-2 that have emerged since the beginning of the year. Cheng says it’s not clear when most of the people in the study were infected, but it’s likely that they recovered from infection with the non-mutant variants, so there’s no way to tell if natural immunity protects against the variants.

She plans to follow up the study to better understand what immunity to SARS-CoV-2 looks like, whether from vaccines or natural infection. One area she hopes to understand better is which parts of the immune system are stimulated by the vaccines. Early data suggest that antibodies are only part of the overall immune response, and that longer-lasting protection is provided by immune players known as T-cells. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, is one of a number of public health experts who have said that the recommended second dose of vaccines made by Pfizer-BioNTech, Moderna and others may be critical for awakening and building this T-cell response.

There are other questions still unanswered as well: “How long can you go without vaccine boosters and not get infected? We know people are getting infected even after getting vaccinated,” says Cheng. “Who are those people and why is it happening? These are big, big questions that only time will tell.”

For now, U.S. health officials continue to recommend two doses of the vaccines from Pfizer-BioNtech and Moderna, as the best way to protect against COVID-19 disease, regardless of whether you’ve been infected or not.