What we know so far about Covid-19 immunity — and what it means for vaccine boosters

Since the start of the pandemic, scientists have been seeking to better understand immunity to the novel coronavirus. How long is a person immune after having Covid-19, after getting vaccinated, or both? And what could long-lasting immunity mean for booster shots?

It’s still too early to tell — but experts are getting closer to cracking the code.

The current wisdom around potential coronavirus vaccine boosters suggests they may be needed at some point — but exactly when is unclear, Dr. Peter Marks, director of the US Food and Drug Administration’s Center for Biologics Evaluation and Research, said on Thursday during a Covid-19 Vaccine Education and Equity Project webinar.

“We’ll have to see where this all interacts. Is it possible we’re going to need a booster at some point? Yes. Is it probable? Yes. Do we know exactly when? No,” Marks said. “But if I had to look at my crystal ball, it’s probably not sooner, hopefully, than a year after being vaccinated, for the average adult.”

And, experts emphasize, anyone who is fully vaccinated currently should still be protected. But the reason why the timeline for potential boosters remains unclear is because scientists still need time to collect the data on how long immunity against Covid-19 may last in the future — and how to factor in future variants.

When a person has “immunity,” in general, that means they have protection against a disease. Active immunity can be acquired either through vaccination or infection. Your immune system develops antibodies either induced by the vaccination or in response to the infection — and either immune response can maintain a “memory.”

Immunity is often measured by the presence of antibodies — proteins made by the immune system to help fight infections, in the blood. They can usually be determined with a laboratory test. But immune systems are much more than just antibodies; they involve a host of players including B cells, which produce antibodies, and T cells, which target infected cells.

Research has shown that both antibodies and T cells might even recognize infections from variants of a pathogen — such as the emerging coronavirus variants circulating in the world today, which, despite key differences that may make them spread more easily, have enough similarities to be recognized by the immune system’s memory.

And even if someone recovered from a previous infection and has a natural immunity, vaccinations can help give their immune memory a boost.

Vaccine makers monitoring immunity

Currently, three coronavirus vaccines are authorized for emergency use in the United States: the two-dose Pfizer/BioNTech vaccine for ages 12 and older; the two-dose Moderna vaccine for ages 18 and older; and the single-dose Johnson & Johnson vaccine for ages 18 and older.

All three companies are investigating the potential use of boosters.

Vaccine makers have been studying whether the immunity these vaccines elicit may wane over long periods of time — say, possibly, after a year or more — and whether they protect as well against coronavirus variants that could emerge and evolve.

If so, a vaccinated person might need a booster dose of vaccine to stay protected against the original coronavirus strain and newly emerging variants — somewhat similar to how a tetanus booster is recommended every 10 years, or different flu vaccines are recommended each year.

When it comes to other viruses, one bout of measles usually leaves someone immune for life. The same was true for smallpox, before that virus was eradicated in the 1970s by a global vaccination campaign. Proper vaccination against measles and smallpox completely protects against infection.

But respiratory viruses such as influenza and coronavirus are trickier. People can catch flu over and over again, and flu vaccines generally provide only partial protection against infection and severe illness, since there are typically multiple influenza viruses circulating due to mutation. Though, the coronavirus has a slower mutation rate than influenza.

Still, doctors are worried that coronavirus may end up being like influenza, which requires a new vaccine every year both because the circulating strains mutate fast, and because immunity from the vaccine wears off quickly.

In the case of coronavirus vaccines, several studies have assessed immune responses elicited by the Moderna and Pfizer vaccines to the original strain of the virus, compared with variants. And “these studies observed modest or no defects in cellular immune recognition of the variants,” according to a webpage on the US Centers for Disease Control and Prevention’s website, updated Thursday.

“Thus, cellular immunity may help limit disease severity in infections caused by variants that partially escape neutralizing antibodies,” according to the CDC.

It is difficult to predict how reduced neutralizing activity may affect Covid-19 vaccine effectiveness — but across studies, antibody neutralizing activity seen among fully vaccinated people has been generally higher than that observed among people who have recovered from Covid-19.

Data from clinical trials suggest that the protection offered by the Pfizer and Moderna coronavirus vaccines likely lasts at least nine months, Marks of the FDA said in April. But experts have been at pains to point out that doesn’t mean immunity stops at nine months. It means that’s the longest volunteers in the trials have been followed to see what their immunity is, and collect data.

Immunity could last much longer; researchers just need the time to evaluate.

The medical community still needs data to determine to what degree immunity may wane over time, Dr. Amesh Adalja, senior scholar at the Johns Hopkins Center for Health Security who was not involved in the studies, told CNN in an email on Thursday.

That degree could be measured as whether people who are fully vaccinated eventually have breakthrough infections at a higher rate, or have infections that are severe enough to require hospitalization.

“To me, that is the threshold,” Adalja said.

Meanwhile, studies into natural immunity from being previously infected with the coronavirus have been ongoing for somewhat longer than vaccine trials.

The latest findings on a long-lasting immunity

Two new studies this week add to the growing body of evidence that suggests natural immunity to the coronavirus after someone recovers from Covid-19 can be long lasting — possibly at least a year. But that doesn’t mean they shouldn’t get vaccinated. It also doesn’t mean immunity will last forever.

One study, published in the journal Nature on Monday, found that immune cells in the bone marrow of people who were infected with coronavirus have a “memory” of the infection that can be long-lived.

The other research, published in the journal EClinicalMedicine on Monday, found that Covid-19 antibodies remained detectable some 10 months after infection among people who had recovered.

Bone marrow cells may maintain a memory of Covid-19 for at least 11 months after someone is infected. These cells are an “essential” source of protective antibodies, according to the new study published in Nature.

Researchers from Washington University in St. Louis examined blood samples from 77 people previously infected with SARS-CoV-2, the virus that causes Covid-19. The researchers found an initial decrease in the presence of Covid-19 antibodies after infection, but between four and 11 months the decline slowed.

The researchers also examined bone marrow samples taken from 19 previously infected patients, about seven and 11 months after infection. The researchers found Covid-19 antibodies in 15 of the 19 patients — and unlike the decline in other antibodies observed, those produced by cells in the bone marrows appeared to remain stable.

“That’s good news that these antibodies are being generated and being maintained,” Ali Ellebedy, an author of the study and associate professor at the Washington University in St. Louis, told CNN’s John Berman on Thursday.

But he added that the findings do not suggest that people who have had Covid-19 no longer need to get vaccinated. Rather, vaccination could enhance the natural immune response even more.

“I think people who had been infected and produce this beautiful memory over time, it would be a great incentive to get the vaccine because now you can put these memory cells into action,” Ellebedy said, adding that having antibodies does not mean a person is completely protected.

“Our data explains why those who experienced mild SARS-CoV-2 infection in the last year are generating such awesome responses to vaccination. It is because of the robust immune memory that they developed after infection,” Ellebedy told CNN in an email on Thursday.

“However, not all previously infected people are the same,” he added. “For many different reasons, some individuals do not generate a robust immune response to infection even after surviving infection. So it is best that they get both vaccinations,” for those receiving a two-dose vaccine.

For those same reasons — whether it be due to age or being immunocompromised — some people might be recommended to follow a different booster schedule than others in the future, if booster shots are eventually needed.

As many as 9 in 10 people infected with the coronavirus develop natural immunity against the virus that is “sustained with little decay” up to 10 months after their initial infection, suggests the EClinicalMedicine study, conducted by researchers at the national clinical laboratory Labcorp.

The researchers found that about 90% recovered Covid-19 patients tested in the study had detectable antibodies by 21 days following infection — and antibody rates remained around 90%, given some variability, up to 300 days.

The researchers analyzed data on 39,086 people who were confirmed to have Covid-19 between March 2020 and January 2021, and had at least one antibody test performed with Labcorp after testing positive for the coronavirus infection.

The data did not include patients’ demographic information or information about how severe a particular Covid-19 case was.

“More research must be done to understand what type and level of antibodies suggest protection from reinfection,” Dr. Brian Caveney, chief medical officer and president of Labcorp Diagnostics, said in a news release on Monday. “But the prolonged presence of certain antibodies is a promising sign as we continue thinking about safely emerging from the pandemic, as well as future vaccinations and the timing of booster shots.”