COVID-19 natural immunity vs. vaccine immunity: What the latest science says

Both have lower risk of reinfection, but response depends, doctors say

FILE - This undated electron microscope image made available by the U.S. National Institutes of Health in February 2020 shows the Novel Coronavirus SARS-CoV-2, yellow, emerging from the surface of cells, blue/pink, cultured in the lab. The sample was isolated from a patient in the U.S. (NIAID-RML via AP, File) (Uncredited)

ORLANDO, Fla. – With the United States coming up on the one-year anniversary of the first publicly available COVID-19 vaccinations, much of the eligible population has received at least one shot, and most children can now get the inoculation as well.

The latest numbers from the Centers for Disease Control and Prevention show 79.7% of people over the age of 12 in the U.S. have had at least one shot as of Nov. 17.

However, vaccine hesitancy and outright refusal of the shots persist in the U.S., in some cases from people who have already had COVID-19 and believe that their natural immunity will protect them.

A growing body of research shows that natural immunity from COVID-19 may not be enough, and if anything, getting vaccinated after recovering from the virus may offer even greater protection against future infection.

The benefit of a robust response

A CDC report released Oct. 29 analyzed several studies and found that both people who are fully vaccinated and unvaccinated people who had COVID-19 generally have a low risk of being infected again for at least six months.

The issue, however, is how robust that immune response is, and how well it keeps a person out of the hospital.

“Most people don’t get a bad case of COVID (when they get infected),” said Chad Neilsen, director of infection prevention at University of Florida Health in Jacksonville. “They get flu-like symptoms, which means you won’t have a robust response.”

People with more severe cases of COVID-19, including hospitalization, have higher antibody levels and therefore more immunity, according to the CDC.

Other factors, such as underlying health conditions or age, appear to weigh on the effectiveness of immune response. If you got an earlier variant of COVID-19, such as the original strain or the alpha variant, your immune response may be less effective against later strains of the virus, such as the delta variant.

A multistate study of COVID-19 hospitalizations at 187 hospitals in the U.S. found that the odds of getting COVID-19 again were 5.5 times higher among unvaccinated people (if infected 90 to 179 days before) than among people who were fully vaccinated, according to a CDC Morbidity and Mortality Weekly Report released in October.

Dr. Bruce Rankin, the medical director for Accel Clinical Research in DeLand, said there are studies that show unvaccinated people are 11 times more likely to have a severe infection with COVID-19 or die from it than the vaccinated.

“The vaccine has been showing some breakthrough with (the delta variant six months after vaccination), but even studies show chances of severe illness or dying is less than 3 percent,” Rankin said, referencing his own clinical trials for Pfizer, Moderna, Johnson & Johnson and Novavax vaccines.

Rankin says no one has 100% immunity from catching COVID-19, and the real effort with the vaccines right now is to prevent severe illness or death.

“They may get COVID infection, but it won’t be as bad,” Rankin said.

Neilsen said the vaccines are designed to maintain an immune response against a broad range of people, ages, and co-morbidities, particularly if those issues can leave a person with a weakened immune system.

“Those who are immunosuppressed have different immunity response right off the get-go, which is why it’s really important to get them a vaccine,” Neilsen said. “They are going to get a worse-off case than someone who is not immunocompromised.”

Rankin said the clinical vaccine trials he conducted accounted for those factors.

“When people came into our trials, initially it was the high-risk group: over 65, people with co-morbidities, people who are high-risk workers, from theme park workers to working in hospitals,” Rankin said. “We took in all their health information, we monitor them every week, we monitor them for any changes with regards to the vaccine or not, so any trends can be monitored much more efficiently.”

The CDC also said there is growing evidence that getting vaccinated after COVID-19 infection greatly enhances protection, which is why the CDC recommends people who have recovered from having the virus should get vaccinated anyway.

“The more times you stimulate your immune system, the better the immune protection,” Rankin said. “So the people with the best protection are those who had COVID and then got vaccinated.”

Rankin says the increased in protection is four to five times greater than those who were infected by never got vaccinated.

“If you’ve had COVID more than six months ago, and you haven’t been vaccinated, vaccination is the most obvious course right now to re-boost your immune system,” Rankin said.

What about studies that disagree on ‘natural immunity’?

Not all studies agree that vaccine immunity is better. A recent observational study in Israel found that prior infection among patients provided greater protection from reinfection than vaccination did.

However, that study also found that risk was lowest among people who were vaccinated after being infected, even with just a single dose of the two-shot Pfizer vaccine.

The CDC identified several factors that could skew the results in favor of infection-induced immunity in the Israel study, including restrictions on the timing of vaccination.

“The Israeli cohort study assessed any positive (COVID-19) test result,” CDC researchers said, comparing the study to the multistate hospitalization review mentioned in the Morbidity and Mortality Weekly Report. “The Israeli cohort study also only examined vaccinations that had occurred 6 months earlier, so the benefit of more recent vaccination was not examined.”

The Israel study also said it only examined the vaccine effectiveness based on the Pfizer option alone, ignoring the effectiveness of other vaccines. The study also did not consider health behavior that could affect the results, such as mask wearing, social distancing and chronic illness.

Both Neilsen and Rankin agree that the type of study used in the Israeli example — an observational study that was not peer reviewed — is also an issue due to the potential for bias and other confounding variables that are built into observational studies.

“Medical science follows peer-reviewed, published articles, stuff that’s reproducible too,” Rankin said. “Observational trials, you’re not able to do that. You try to take out all the variables and reduce influence bias. With observational trials, it’s already built in.”

Neilsen said that peer-reviewed studies are the backbone of scientific and medical research.

“When an article like this Israel study is preprint, when other scientists have yet to review it, it means the study doesn’t have the gold stamp,” Neilsen said. “The especially newsworthy ones have to have that gold stamp, because they have to have that rigor.”

Neilsen also says one should never look to one study alone to understand something in the science community, especially an evolving situation like COVID-19.

“Meta-analyses are extremely useful, and the CDC does a lot of them, because it puts all the studies in a pot and tries to make sense of what the research says altogether, good and bad,” Neilsen said.

It should be noted that the report mentioned at the beginning of this story is not a meta-analysis according to the CDC, even though it looks at several studies, including the Israeli example.

Why do vaccinated people need boosters?

The CDC is recommending booster shots for some Pfizer or Moderna vaccine recipients six months after being fully vaccinated:

  • People 65 years or older
  • Adults with underlying medical conditions
  • Adults who live in long-term care settings
  • Adults who work or live in high-risk settings

Recipients of the Johnson & Johnson vaccine are eligible for a booster shot at least 2 months after the first dose.

Neilsen says that vaccine-induced immunity will wane over time, so booster shots are there to reactivate the immune response.

“Most research is pointing to six to eight months of robust immunity, so when you get the booster shot it reactivates your immunity against whatever variant may be coming,” Neilsen said.

At Accel Clinical Research, vaccine trial patients are still being checked and are now getting boosters. Rankin said that, after boosting, many studies show that antibody counts can be four to five-fold higher.

“All these trials were geared for 24 months, because we have to gauge safety and effectiveness, and also how long they last,” Rankin said. “We had data at six months, and now we’re bringing them back in for a year (update) to look at antibodies and provide boosters. So now we’ll be monitoring them at least another year from their boosters.”

When it comes to the next round of boosters, Neilsen said that’s still being figured out.

“It really depends on whether COVID is going to stick around,” Neilsen said. “We give you a flu booster every year, I don’t think people think of it that way. But we do because the flu changes every year.”

Neilsen said that respiratory viruses come and go, but he doesn’t know if COVID-19 is going to do the same.

Rankin, on the other hand, believes that COVID-19 is here to stay, and that it must be planned around.

“I would say that the coronavirus is not going to go away,” Rankin said. “There are going to be groups of people, those over 65 or immunocompromised, who are going to need to be re-boosted just because of a lacking immune system.”

Rankin also predicted that a COVID-19 booster could be paired or even combined with annual flu shots in the future.

“The FDA would require all-new testing in order to do that. So, they would have to go through new trials,” Rankin said.

About the Author:

Christie joined the ClickOrlando team in November 2021.