How good is natural immunity?

As provincial governments across Canada intensify efforts to increase vaccinations, mandating the shots for some professionals and requiring the public to be vaccinated to enter certain establishments, many people who have recovered from COVID-19 say they have been overlooked.

“Why are we not being recognized as people who have adequate immunity?” Albertan country star Paul Brandt asked on Facebook on Sept. 17. A similar question prompted Alberta Premier Jason Kenney to say that his government was looking into exempting people who had COVID-19 from requiring proof of vaccination under the province’s vaccine passport system, though such an exemption would not be coming anytime soon, if at all.

This raises an important question: is the immunity that comes from having caught COVID-19, known as “natural immunity,” as good as the immunity from vaccination?

The short answer is that it may well be, at least for some, but there are caveats. “The trouble is that there’s so much that we don’t know about the immune response to COVID-19,” says Ameeta Singh, an infectious diseases specialist at the University of Alberta. For this reason, immunologists and other medical professionals generally still recommend that those who have had COVID-19 get vaccinated.

To better understand how these two kinds of immunity stack up, we first need to grasp the basics of the immune system.

How do you develop immunity to the coronavirus?                                     

When SARS-CoV-2, the virus that causes COVID-19, enters your body, it uses its infamous spike proteins to bind to certain receptors on your cells and, as if picking a lock, it hijacks the cells so that they start producing more viruses. Your immune system quickly counterattacks in part with an onslaught of imprecise anti-viral cells and molecules while, within seven to ten days, your adaptive immune system starts building more targeted, lethal armaments: B cells start manufacturing antibodies, Y-shaped proteins that latch onto the SARS-CoV-2 virus, both flagging it for destruction and preventing it from infecting your cells; killer T cells destroy infected cells pumping out more of the virus.

After the infection has been routed, your immune system winds down. The antibodies in your blood gradually decrease before leveling off. Many B cells and T cells die. But your immune system is still prepared for future battle with SARS-CoV-2: certain cells, known as memory B cells and memory T cells, remember the virus they vanquished. If it reappears, not only will your lingering antibodies swarm it, but within days your memory B cells and T cells will once again start churning out more antibodies and destroying infected cells.

SARS-CoV-2 infection exposes your immune system to the entire virus, while the current COVID-19 vaccines work by tricking your cells into manufacturing just the virus’s spike protein. Your immune system then reacts to these spike proteins and any cells displaying them similarly to how it would respond to an infection. This way, if the virus does infect you, it will come up against the antibodies, memory B cells and memory T cells made when you were vaccinated. They will recognize the virus’s spike protein and attack.

Now let’s compare natural immunity and vaccine-induced immunity in three critical areas: their strength; how long they last; and how well they fend off variants.

How strong is each type of immunity?

Both vaccine-induced and natural immunity usually confer strong protection, especially against severe sickness and death.

In clinical trials, Pfizer and Moderna were around 95 per cent effective at preventing SARS-CoV-2 infection, while AstraZeneca was about 60 per cent effective. Data on the vaccines’ post-rollout performance, which can differ from their performance in clinical trials, shows them holding strong, at least at the time the data were collected. One study, not yet peer-reviewed, found mRNA vaccines to be around 90 per cent effective at preventing symptomatic illness caused by Alpha, the variant first identified in the U.K., while Pfizer was 88 per cent effective against Delta, first detected in India. AstraZeneca, on the other hand, was more than 70 per cent effective against Alpha and 67 per cent effective against Delta. The vaccines do even better at preventing serious illness: mRNA vaccines were 98 per cent effective, while a recent Phase 3 clinical trial found AstraZeneca to be 94.2 per cent effective against hospitalization.

Natural immunity, it turns out, “may provide similar protection against symptomatic disease as vaccination,” states a WHO report from this May, with “current evidence point(ing) to most individuals developing strong protective immune responses following natural infection.” One study found that prior infection with SARS-CoV-2 “induces effective immunity to future infections in most individuals.”

There are some caveats, though. For one, the strength of natural immunity seems more variable. Scientists are still trying to identify a “correlate of protection,” a metric of how strong someone’s immunity is, but evidence is mounting that such a correlate might lie in the amount of antibodies in a person’s blood. If a certain level of antibodies proves to be a reliable correlate of protection, people who have natural immunity should take heed: “Vaccinated people will keep an average higher level than the average of naturally infected people,” explains Theodora Hatziioannou, a virologist at Rockefeller University who has been studying immunity to COVID-19. “The vaccinated always stay, as an average, consistently higher than the naturally infected.”

“Vaccination is more standardized,” says Fabienne Brilot-Turville, an immunologist at the University of Sydney who has also studied natural immunity to COVID-19. “Everyone receives a similar dose; therefore, responses would be expected to be more similar.”

People who were previously infected should therefore get vaccinated, she says. “The patch-work quilt of immunity following infection can be addressed through vaccination.”

What’s more, you might not have much immunity to COVID-19 if you were infected by the virus but did not develop any symptoms, or only mild ones. “Individuals with mild or asymptomatic infection tend to have lower antibody levels than those with severe disease,” states the WHO report. While this correlation is enigmatic, with a recent study finding that even asymptomatic and mild cases of COVID-19 appeared to generate significant antibody levels, “There’s a fair bit of evidence that people who had asymptomatic infection versus severe COVID have very different neutralizing antibody responses,” says Andrew McGuire, a scientist at the Fred Hutchinson Research Center who has studied COVID-19 immunity.

“Our data and data from many other labs show that a good number of people with very mild symptoms have close to undetectable levels of neutralizing antibodies,” Hatziioannou says. “A few do not even seroconvert,” meaning they don’t develop detectable antibodies.

So, if you once had COVID-19, it might not be safe to assume you’re adequately protected from it, especially if your previous brush with the virus was mild.

How long-lasting is each type of immunity?

Fortunately, both kinds of immunity offer protection for at least six months, and potentially much longer. It’s still unclear just how long it will ultimately last, however: as with other human coronaviruses, some scientists suspect this protection won’t be lifelong, putting anyone who has been previously infected or vaccinated at risk for re-infection or breakthrough infection.

What we do know so far is promising, though. Natural immunity seems to “remain robust and protective against reinfection for at least 6-8 months after infection,” the WHO report stated. Moreover, a study in Nature has picked up on antibodies in the blood of people 11 months after they were infected, even though their infections were only mild; a recent study detected neutralizing antibodies in one group of people 13 months after they were diagnosed with COVID-19. Another study, detecting the stable presence of memory B cells up to 12 months post-infection, concluded that natural immunity appeared “very long lasting.”

Vaccines seem to be holding strong too: researchers have found high antibody levels six months after vaccination with Moderna, and another study found that both mRNA vaccines produce immune responses that could last years, the New York Times reported. As for AstraZeneca, a pre-print report from Public Health England indicates that the protection it provides against hospitalization due to Delta generally remains good – just under 80 per cent – after 20 weeks.

You may be wondering how this is compatible with recent concern over so-called “waning immunity,” which, as The Atlantic’s Katherine Wu writes, has “made it seem as though we’re doomed to chase SARS-CoV-2 with shot after shot after shot, as if vaccine protections were slipping through our fingers like so much sand.” While it’s true that the vaccines’ protection against infection and even mild symptomatic COVID-19 appears to decline over time, this is not necessarily cause for alarm.

Recall that it’s normal for your antibodies to dwindle over time. This effectively means that there are fewer guards on patrol. So, if SARS-CoV-2 enters your body, it’s easier for it to start infecting cells, even to the point of causing minor symptoms. But you’ve already built solid immunological fortifications, the memory B cells and T cells. Protection against severe illness and death consequently remains high: an August CDC study found that for mRNA vaccines, protection against hospitalization had barely decreased after six months. While some preliminary research, not yet peer-reviewed, suggests a small dip in protection against hospitalization and death may be occurring, as Nature reports, “globally, there is as yet no indication that the rates of severe illness among the vaccinated are spiking in any appreciable way.”

How does each type of immunity fare against variants?

The science is not yet clear when it comes to which immune response is better against variants. “The story is messy,” says Katelyn Jetelina, an epidemiologist at the University of Texas Health Science Center at Houston who has written about natural immunity and variants.

The vaccines were designed to induce immunity against the original strain of SARS-CoV-2 that arose in late 2019 in Wuhan, China, but they seem to be holding up, albeit less effectively, against the variants that have prevailed in Canada: Alpha and, more recently, Delta.

Against Alpha, AstraZeneca was more than 70 per cent effective at preventing symptomatic illness, as noted above, while the mRNA vaccines were around 90 per cent effective.

Against Delta, though, natural immunity might have an edge, at least compared to Pfizer. That is the preliminary finding of one study, not yet peer-reviewed, that has garnered lots of attention—including from Anthony Fauci, chief medical advisor to President Joe Biden, who said that it prompted him and his colleagues to begin discussing whether prior infection should exempt someone from vaccination requirements.

Now, the study’s findings might be modified during peer review. Healthy Debate’s own deputy editor, epidemiologist Catharine Chambers, doesn’t think the study authors “adequately accounted for time from vaccination or infection or controlled for potential confounders in their analysis.”

Moreover, “These findings should not be taken as an endorsement that getting infected is a better overall option for protection than the highly effective vaccines,” the John Hopkins Bloomberg School of Public Health noted, “as only those who survived initial infection were eligible for analysis.”

That said, the findings appear consistent with recent research suggesting that antibodies produced by infection might respond better to viral mutations than antibodies produced by vaccination, says Paul Bieniasz, a virologist at Rockefeller University. This is because infection might expose the immune system to the virus longer, prompting its B cells to mature to produce antibodies that better recognize and bind to the virus, Bieniasz suspects.

During a SARS-CoV-2 infection, your immune system also studies the entire virus, not just the simulated spike protein of the vaccines, which probably gives your T cells greater breadth, says McGuire. “That probably plays a pretty important role.”

Other research, however, has found that antibodies produced by the Moderna vaccine might actually adapt better to mutations in the part of the spike protein that binds to human cells than those induced by infection. Another study also found that people vaccinated with Moderna had higher levels of antibodies capable of neutralizing the Alpha variant and a viral mutation known as N501Y, which makes that variant more transmissible. This mutation is also found in Beta and Gamma, the variants first detected in South Africa and Brazil. (Complicating this picture further, though, is a recent study, not yet peer-reviewed, that found that a significant portion of a group of people vaccinated with Pfizer had undetectable levels of neutralizing antibodies that could fight off Delta, Beta, and Mu – first identified in Colombia – six months after their second dose).

“Science takes time to figure this out,” says Jetelina. “That’s what’s happening here.”

Getting vaccinated after being infected may give you the best immunity of all

Your immune system appears to become exceptionally powerful if you get at least one dose of an mRNA vaccine after being infected, a notion supported by a recent CDC study that found that, among previously infected Kentuckians, those who did not subsequently get vaccinated were 2.34 times more likely to get re-infected than those who did.

Other recent research attests to just how impressive this kind of immunity can be: in one recent study in Science, researchers observed that antibodies from previously infected people neutralized the original SARS-CoV-2 virus and sporadically neutralized Beta. But the antibodies of those who had been infected and then received one mRNA vaccine dose exploded in number and not only neutralized other variants, but also SARS-CoV-1, the virus that caused the SARS outbreak in 2003, which is markedly distinct from SARS-CoV-2. “Our study highlights the importance of vaccinating both uninfected and previously infected persons,” the researchers concluded.

It’s not yet clear whether a similar effect would occur among those who got vaccinated and were then infected, or who were vaccinated with AstraZeneca, say Bieniasz and Hatziioannou, who co-authored a recent study that came to similar conclusions.

“There’s so much unknown right now,” says McGuire, who worked on the Science study. “It’s still the early days.”

Paul Brandt, the country star, and his wife had a long conversation that touched on some of these unknowns with Saskatchewan-based virologist Angela Rasmussen after his Facebook post. Rasmussen convinced them of “the need for COVID-recovered people to vaccinate,” Brandt later tweeted. “This is a conversation that needs to be happening now.”

This article has been updated to include new information.