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How Omicron Upended What We Thought We Knew About Natural Immunity

After dizzily swelling for weeks, COVID-19 cases seem to be leveling off in New York and Chicago. In the greater Boston area, the amount of SARS-CoV-2 found in wastewater is going down as quickly as it had gone up. The hard part isn’t over yet, but the omicron wave is starting to break and roll back out to sea. Soon we’ll see if any treasures are left behind in the tide pool.

Between Dec. 1 and Jan. 17, at least 18 million Americans contracted COVID. Data suggests that the vast majority of those cases were in unvaccinated people, but plenty of people who got their primary series of the vaccine also caught the immunity-evading omicron variant. By the time this wave is over, American bodies will know this virus like never before. But will the survivors gain anything from having had the disease? After all, there will be more variants in the future. Could the hard-earned immunity we’ve gained from omicron help fight them off? Could this wave be the last? 

On Monday, White House chief medical adviser Anthony Fauci said it’s too soon to answer these questions. Scientists we spoke to agreed. But they also said the reason these questions were so difficult to answer was because of an issue that hasn’t always gotten much attention in the public sphere: the immunity provided by a COVID infection itself. Scientists have learned a lot about this “natural immunity” since the pandemic began. But omicron has upended many of those expectations, and the more we learn about this variant, the less clear it is what we should expect for the future of the virus and our immunity to it. 

Scientists have been studying infection-induced immunity since COVID first emerged. In fact, it was the only kind of immunity anyone could really study at that point, said John Moore, a professor of microbiology and immunology at Cornell University’s Weill Cornell Medical College. And while there are now many more studies on vaccine-induced immunity thanks to clinical trials and easily trackable vaccinated populations like medical staff, there’s a lot that can be said about natural immunity, pre-omicron, with a reasonable amount of certainty. 

One important takeaway from all that pre-omicron research: Infection-induced immunity and vaccine-induced immunity are pretty similar. On the whole, studies found that the efficacy of infection-induced immunity was about the same as what you’d get from a two-dose mRNA vaccine, and sometimes higher. For example, research from the U.K., in which a few hundred thousand participants were followed in a large-scale longitudinal survey, found that prior to May 16, having had two doses of the vaccine (regardless of the type) reduced the risk of testing positive by 79 percent, while being unvaccinated and having had a previous infection reduced the risk by 65 percent. After the delta variant became dominant,1 vaccination became less effective, reducing the risk by 67 percent, while a previous infection reduced the risk by 71 percent. 

Likewise, both kinds of immunity seemed to wane over time — though Moore said infection-induced immunity might take longer to decline because a vaccination happens nearly all at once, while an infection takes longer to go through a process of growing, declining and finally being cleared from the body. “But it’s also not radically different [from antibody titers to vaccination]. It’s not measured in years, but months,” he said. 

This is why some countries, including the member states of the European Union, treat documented recovery from COVID-19 as functionally the same as vaccination in their “vaccine passport” systems. 

Still, vaccine-induced immunity is a better choice, not because it produces a stronger immunity, but because it enables you to get the immunity without the side effects and risks that come along with illness — like a greater risk of stillbirth if you’re pregnant, or long COVID, hospitalization and death in general. 

The pre-omicron research also indicated another downside to natural immunity: namely, that it can be more variable. All immunity differs from person to person and holds up better against some variants than others. But infection-induced immunity can also be more or less effective depending on how severe your case of COVID was, explained John Dennehy, a professor of biology at the City University of New York’s Graduate Center. Since the earliest studies, scientists have found evidence that more severe illnesses produce a higher antibody response, while mild cases end up producing much less.

Then came omicron. The public desire for information on omicron is moving faster than science can produce, but we do know that this variant escapes natural immunity as easily as it does vaccine immunity. Omicron carries a lot of mutations that make it able to evade antibodies — and it doesn’t really matter how you got those antibodies in the first place, said Jeffrey Klausner, a professor of medicine in the Division of Infectious Diseases at UCLA’s David Geffen School of Medicine. 

Beyond that, the picture is murky. For example, we know milder infections have, with past strains, produced less effective immunity. If a hallmark of omicron is milder infections — and that’s the main reason why there’s so much chatter that it might just be better to get this variant and get some natural immunity — how much immunity can anyone really expect to come out of those mild infections with? “We’re going to know for sure in a few weeks because a ton of preprint is coming out about it, but I don’t know the answer today,” Moore said. It’s information journalists can come back and update you on later, but it makes informed speculation hard now. (Meanwhile, keep an eye on our COVID-19 research tracker.)

The same holds true when you start trying to parse out what vaccinated people can expect from a breakthrough case of omicron. The combination of vaccine and infection-induced immunity has been shown to produce a hybrid that is probably more effective than either type alone — but, again, that research came from pre-omicron studies. Is a breakthrough case as good as a booster? If you’re going to get a booster after you’ve had a breakthrough case, how long should you wait? Those are questions scientists don’t have the answers to yet, partly because there’s no clear through line of what to expect once you’re dealing with omicron.

“Maybe your readers are right in being confused, because we don’t really know how long-lasting the immunity you get from omicron will be,” said David Thomas, the director of the Division of Infectious Diseases at Johns Hopkins Medicine. 

Which brings us to the biggest question of all: Will the many infections, reinfections and breakthrough infections associated with omicron maybe — finally — put us in a better position for a well-protected, safer society? Maybe even a society that doesn’t have any more big waves crashing on its head? Theoretically, yes, Klausner told me. And he’s optimistic that it will. Thomas and Dennehy, on the other hand, were more cautious. After all, Dennehy pointed out, there’s no guarantee that future strains will be related to omicron. If omicron is different enough from delta that it evades immunity from that previous variant, what happens if a future variant comes along that’s evolved from delta and not omicron? It’s not unreasonable to expect a whole new wave.

And what does Moore think? He was just ready to take a pause from speculation and get some data before anyone starts making decisions for themselves or for society. “I’m fed up with winging answers to reporters like yourself, because I don’t know the answer,” he said. “None of us know for sure.”

Footnotes

  1. May 17 to Aug. 14 in this study.

Maggie Koerth is a senior science writer for FiveThirtyEight.

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