One Dose for the Previously Infected? | MedPage Today - MedPage Today

Facing down the more transmissible Delta variant, it seems wise to equip oneself with as much protection against COVID-19 as possible -- especially in a nation with robust vaccine supply.

But legitimate scientific questions have been raised as to whether people who've been previously infected with SARS-CoV-2 need just one dose of an mRNA vaccine, and some supply-constrained countries -- including Germany, Italy, and France -- have made it official policy that this group needs just one dose.

So what does the science say about the protection conferred by just one dose in this population?

Early work does seem to suggest that one shot in a previously infected person provides immunity that's comparable to two doses in an infection-naive patient.

But it's indeed early work. Does that protection last as long as that from a two-dose series? Is it enough to stand up to Delta? Those are just some of the questions that remain, but more researchers are becoming convinced by the evidence that's available.

Interpreting the Evidence

Paul Offit, MD, of Children's Hospital Philadelphia, is one of the world's top experts on vaccines, having developed one himself. You won't find a more "pro-vaccine" source. Yet last week, Offit said on the ZDoggMD show that those with prior infection probably would be sufficiently protected with just one dose.

"If you've been naturally infected and you get a dose of an mRNA vaccine -- and there are now a few studies that have shown this -- you act as if you got your second dose," Offit said. "You get a clear booster response. So you probably only need one dose of an mRNA vaccine."

Indeed, there are several studies, most often single-center experiences with mRNA vaccines, that show one dose in this population confers protection similar to that of two doses among the infection-naive.

That was the case for a University of Pennsylvania study of 44 people published in Science Immunology that found strong antibody and memory B cell responses after just one dose, and a Cedars-Sinai study of about 260 healthcare workers published in Nature Medicine that showed a good antibody response in recovered patients after one dose.

A Mount Sinai study of 110 participants published as a letter in the New England Journal of Medicine also showed robust immune response in previously infected individuals after one dose.

In all of these studies, all of which were published in April, the second shot didn't confer additional advantage in terms of immunogenicity for the previously infected.

There's also evidence that the immunity conferred by natural infection is strong on its own. Offit cited a Nature study published in May that found bone marrow plasma cells -- which make antibodies -- directed against the virus remain robust up to 8 months after infection. A paper in Science also showed sufficient levels of B cells and T cells against SARS-CoV-2 up to 8 months after infection.

Monica Gandhi, MD, MPH, an infectious disease expert at the University of California San Francisco, said studies looking at reinfection also appear to suggest long-term protection. She cited the U.K.'s SIREN study, published in The Lancet, which found very low rates of reinfection, along with studies from the U.S. (published in Clinical Infectious Diseases) and Qatar (published as a research letter in JAMA).

She also cited a Cleveland Clinic study published as a preprint on medRxiv that found low reinfection rates among previously infected employees who remained unvaccinated (though the Clinic issued a statement about the preliminary nature of the results), and an Israeli study also published in medRxiv that also found high levels of protection against new infection for those previously infected.

"The data are very suggestive that you are really protected against reinfection with natural infection," Gandhi told MedPage Today.

Offit agreed: "I think one could reasonably make the argument that if you've been naturally infected, I think you are very likely protected against severe critical disease, meaning the kind of disease that will cause you to be hospitalized," he said on ZDoggMD. (Offit confirmed his comments to MedPage Today.)

But Gandhi noted that if she were advising a family member with prior infection, she might note evidence of improved T cell differentiation in the nasopharynx, for instance, if they get at least one dose of the vaccine.

"If it's still circulating at such high levels, why not do everything to increase immunity?" Gandhi said.

'We Need a Lot of Humility'

If the evidence is there for strong protection from natural immunity and for one dose in the previously infected, why isn't that strategy being deployed more widely in the U.S.?

Offit's take was that it was likely "more for bureaucratic reasons than anything else."

"Because now you have to test everybody to see if they've been previously infected," he said on ZDoggMD. "It added another layer to an already complicated program, so that wasn't done."

Eleanor Riley, PhD, an immunologist at the University of Edinburgh in Scotland, told The BMJ that "incorporating this into a mass vaccination program may be logistically complex and it may be safer, overall, to ensure that everyone gets two doses."

There are also the challenges of antibody testing itself. Questions about the accuracy of these tests have been raised, and the level of antibody required for definitive protection isn't yet established. Going a step further, testing for B cell or T cell response in the absence of antibodies wouldn't be feasible at a population level.

What about a previous positive PCR test? Could that serve as proof of prior infection? What if that infection was only mild? Would the patient have mounted a sufficient immune response?

Also, with both antibody and PCR testing, a wider program of dosing based on prior infection status could easily turn into an honor system, and given the U.S. track record on masking policy, that strategy is questionable, some experts said.

The Delta variant looms over all of these questions. Much of the research on one dose in the previously infected was done before Delta was the dominant strain. With evidence mounting that Delta is twice as transmissible as the original strain of the virus, and has a viral load that's 1,000 times higher, would one dose in this population still provide sufficient immunogenicity to stand up to Delta?

While vaccine immunity still appears to be standing up well so far, there's no guarantee a future variant won't escape immunity.

"There are a lot of unknowns," Gandhi said. "We need a lot of humility."

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  Kristina Fiore leads MedPage's enterprise & investigative reporting team. She's been a medical journalist for more than a decade and her work has been recognized by Barlett & Steele, AHCJ, SABEW, and others. Send story tips to k.fiore@medpagetoday.com. Follow

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