MILWAUKEE — Tens of millions of Americans have survived a COVID-19 infection. 

Some of those survivors are relying on their natural immunity to ward off catching the virus again: In a recent Gallup survey, having a previous COVID-19 infection was one of the main reasons Americans said they didn’t plan to get the shots. 

But health experts emphasize that everyone who’s eligible for a COVID-19 vaccine should get one — even if they’ve recovered from an infection in the past. Studies suggest that vaccines can offer stronger protection than natural immunity alone, especially against the viral variants that are driving surges right now.

“If you have had COVID-19 before, please still get vaccinated,” CDC Director Dr. Rochelle Walensky said in a statement. “Getting the vaccine is the best way to protect yourself and others around you, especially as the more contagious delta variant spreads around the country.”

Here, we break down the science behind that guidance.

Understanding the immune response

When a new virus comes along that your body hasn’t encountered before, the immune system has a hard time fighting off the invader, said Dr. Mary Beth Graham, an infectious disease specialist at Froedtert & the Medical College of Wisconsin.

Either a natural infection, or a vaccine can help the immune system get familiar with a new threat — though a vaccine does so with a copied piece of the virus that can’t actually infect you. That way, if you bump into the virus again, your body will be more ready to defend itself.

And that immune response, whether from an infection or a vaccine, has different layers, Graham said.

“When we’re exposed to a viral pathogen,” she said, “there are multiple parts of the immune system that are stimulated.”

The antibodies, which we’ve heard a lot about when it comes to COVID-19, are “the immediate guys who are there” — the fighters that show up to neutralize the virus right away, Graham said. These antibodies can keep circulating for a while after an initial infection, but they’re expected to wane over time.

The immune system also stores long-term backups in the form of memory T and B cells, Graham explained. These cells are able to hang out in the body and be called back into action if you encounter the same virus in the future. 

Studies suggest an immune boost

So how does this immune response compare between natural and vaccinated people?

In either case, the body will react with this multi-layered approach, Graham said, pumping out antibodies as well as T and B cells.

Some studies have found that the vaccine may lead to higher antibody levels than a natural COVID-19 infection — although Graham stressed that it’s hard to make apples-to-apples comparisons with antibody levels, since the immune response is so complex.

There is some evidence that the immune response after the vaccine is better equipped to deal with different variants of the coronavirus, Graham said.

An NIH-supported study this summer found that post-vaccine antibodies could target a wider range of mutations on the virus’s spike compared to post-infection antibodies. 

That adaptability is important for lasting protection, especially now that we are seeing the delta variant drive new cases in the U.S., Graham said. An immune response to an earlier form of the virus might not protect as well against a delta reinfection.

“Back at the beginning of the pandemic, if somebody had the original SARS-CoV-2 that was circulating, that immune response to that is unlikely to provide much protection against delta,” Graham said. “Whereas with vaccine, the stimulation of the immune system is such that the antibodies that are made are more broad.”

The CDC study from earlier this month added more direct evidence that vaccines make a difference, even for recovered COVID-19 patients.

Researchers looked at hundreds of Kentucky residents who had tested positive for the virus at some point in 2020 and then were reinfected in 2021. Some of those recovered patients had gotten vaccinated after their first bout with the virus, while others opted out.

Out of these groups, the researchers found that unvaccinated COVID-19 survivors were 2.34 times more likely to get reinfected, compared to those who doubled up with a vaccine on top of their natural immunity.

“These findings suggest that among persons with previous SARS-CoV-2 infection, full vaccination provides additional protection against reinfection,” the authors concluded.

Those who have had a COVID-19 infection may get even better-than-average protection from the vaccines: A recent study found that, after getting their shots, COVID-19 survivors had a higher level of antibodies than those who hadn’t been infected.

Risks and rewards

People who have had COVID-19 may be more likely to experience some of the flu-like effects from a vaccine, like fever, headache and chills. 

Still, the response varies from person to person, Graham said, and some side effects are a normal part of the post-vaccine experience.

A lot of online reports focus on “the extremes of awfulness,” she said — “which then leads to more misinformation, which leads to more distrust, which leads to more fear.” 

But the vaccines are safe and recommended for those who have had COVID-19 in the past. Graham said many of her patients didn’t feel any significant side effects after shots, even if they had a prior infection.

The FDA this week even underscored its confidence in the Pfizer vaccine, offering full approval to the shots after looking at extended safety and efficacy data.

All in all, research so far suggests that a COVID-19 vaccine boosts the protection you’d have after a natural infection and keeps you safer from reinfection — especially amid the surge of variant cases. And it does so in a way that’s safe, Graham emphasized.

"Vaccines are highly efficacious," infectious disease expert Dr. Anthony Fauci said earlier this year. "They are better than the traditional response you get from natural infection."