As the U.S. grapples with its troubled vaccine rollout, an alarming increase in coronavirus cases across the nation has resurfaced a long-simmering question: Do people who’ve already had COVID-19 need to be vaccinated?
Natural immunity is a powerful force against certain diseases, such as chickenpox and measles. Surviving a natural measles infection can yield immunity that is comparable—or in some cases, superior—to vaccination, says Ruth Karron, a pediatrician and professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore.
But first, of course, the patient has to survive.
It’s also not yet crystal clear whether immunity from contracting COVID-19 is as powerful as the protection of a vaccine. What is evident is that the available vaccines mount crucial defenses against severe disease and death—even against more contagious variants such as Delta. And research shows that even a single dose of an mRNA vaccine from Moderna or Pfizer-BioNTech boosts immunity for people who’ve had the disease.
“I would recommend to anyone who hasn’t been vaccinated to go ahead and get vaccinated as soon as they can,” says Allison Greaney, a researcher at Fred Hutchinson Cancer Research Center in Seattle, adding that the vaccines “protect us so well against a very dangerous virus.”
More robust antibodies
At Fred Hutchinson, graduate student Greaney led a research team that published a recent study suggesting vaccines give people an important edge over natural immunity. The team looked at the antibodies of people who had recovered from COVID-19, as well as people who’d received two doses of the Moderna mRNA vaccine as part of the company’s phase one trial.
The researchers found that both groups generated antibodies that targeted the receptor binding domain, or RBD. As its name suggests, this part of the SARS-COV-2 virus helps it stick to and ultimately gain entry to human cells, causing an infection. If antibodies attach to the RBD instead, they can neutralize the virus.
The research revealed that the antibodies of recovered COVID-19 patients stuck mostly to an area of the RBD that includes the site E484—a portion of the virus that has mutated in some variants. By contrast, the antibodies in vaccinated people bound more broadly across the domain, allowing them to target areas that are still present in some variants, including Beta, Gamma, and Delta.
SARS-COV-2 takes “great pains” to mask its RBD, using molecular trickery to make the region hard for antibodies to find, because it’s the most vulnerable part of the virus, says Amy Hartman, an associate professor of infectious disease and microbiology at the University of Pittsburgh. But mRNA vaccines are built to target the RBD and send potent antibodies to it. And the new findings suggest that immunity from mRNA vaccines “seems to be more robust than natural immunity in many cases,” Greaney says.
Researchers already knew that COVID-19 vaccines “reliably induce antibody levels” that are as high or even higher than those of people who have recovered from severe cases of coronavirus, says Karron, who was not part of the new study. This Fred Hutchinson team’s work shows that vaccination “gives us both more antibodies and better antibodies,” she adds. “It’s a quantity and quality issue.”
So, why the debate?
Other research, however, makes the case that natural immunity to COVID-19 might be robust. A team of researchers evaluated 254 people up to eight months after they had recovered from COVID-19 and found they had “durable, broad-based immune responses.” That was true even for those who had suffered only mild disease, according to their study, which was published last month.
Scientists know that other diseases can confer lasting natural immunity. After a single chickenpox infection, a person will likely have life-long immunity against the itchy and sometimes-deadly disease. To get the same long-lasting immunity from a vaccine, that person would need two shots, given years apart.
But before chickenpox vaccines were developed, about 10,000 U.S. children and adults were hospitalized each year with the disease, with symptoms including lung and blood infections.
For SARS-CoV-2, “I can’t make the case that [vaccination or natural immunity] is necessarily better than the other based on any knowledge that I actually possess about this particular virus,” says Charlotte Cunningham-Rundles, the David S. Gottesman Professor of Immunology at the Mount Sinai School of Medicine.
But she hastens to add: “I don't think anyone’s collected enough data to say that somebody who’s had this virus on their own does not need to get vaccinated.”
Karron also notes that one of the “great unsolved mysteries” of SARS-CoV-2 is why some people have asymptomatic or mild disease, while others are afflicted with severe infections. In the same vein, scientists are still struggling to understand when and why certain people will develop stronger immune responses than others.
For instance, says Hartman, studies have shown that some recovered patients can mount effective defenses against COVID-19, but antibody levels dropped rapidly in others who were infected. Scientists are still gathering data and racing to answer this key question and others, such as how long immunity lasts from vaccines or from natural infection.
With vaccination, most people are all but guaranteed to have a strong immune response—and that includes people who’ve already contracted COVID-19. Multiple studies have shown that even a single dose of an mRNA vaccine boosts antibody levels in recovered patients, giving them the same peak response that two shots afford people who haven’t had the disease.
Today, more than 97 percent of people hospitalized for COVID-19 in the U.S. are unvaccinated. And while a small percentage of vaccinated people have been infected with the virus, their cases are overwhelmingly mild. On Monday, U.S. Senator Lindsey Graham, who was vaccinated in December, announced that he had tested positive for COVID-19 after experiencing only mild symptoms. “I am very glad I was vaccinated,” the South Carolina Republican said in a statement, “because without vaccination, I am certain I would not feel as well as I do now. My symptoms would be far worse.”
The CDC reports 0.0018 percent of COVID-19 deaths from December 14, 2020, to July 19 were among the vaccinated. And that, experts say, is proof the vaccines work.
“For many pathogens, we’re a bit humble,” Karron says. For some diseases, such as HIV or malaria, “you don’t want to get infected at all,” she says. “But for a lot of pathogens—and especially for things like respiratory pathogens, like COVID-19—our goals are a little more modest. Our goal is really to prevent severe disease and death.”