A Blog by Jonathan Low

 

Feb 27, 2021

Does Anyone Know How Great Post-Vaccination Infection Risk May Be?

No, no one is sure yet. But optimism appears to be more warranted than pessimism. JL

James Hamblin reports in The Atlantic:

The current batch of COVID-19 vaccines won’t stop viral transmission outright. But it’s also safe to assume that they will reduce that transmission to some extent, because they impede viral replication. “We will absolutely get to a point when we can say that vaccinated people don’t need to wear masks." But that will be driven largely by changes in the number of cases, and in the vaccination rate. The sooner we can drive the former down and the latter up, the sooner normalcy returns. 

Every day, more than 1 million American deltoids are being loaded with a vaccine. The ensuing immune response has proved to be extremely effective—essentially perfect—at preventing severe cases of COVID-19. And now, with yet another highly effective vaccine on the verge of approval, that pace should further accelerate in the weeks to come.

This is creating a legion of people who no longer need to fear getting sick, and are desperate to return to “normal” life. Yet the messaging on whether they might still carry and spread the disease—and thus whether it’s really safe for them to resume their unmasked, un-distanced lives—has been oblique. Anthony Fauci said last week on CNN that “it is conceivable, maybe likely,” that vaccinated people can get infected with the coronavirus and then spread it to someone else, and that more will be known about this likelihood “in some time, as we do some follow-up studies.” CDC Director Rochelle Walensky had been no more definitive on Meet the Press a few days before, where she told the host, “We don’t have a lot of data yet to inform exactly the question that you’re asking.”

At this point in the pandemic, with deliverance in sight for so many people, the vagueness can justifiably be maddening. For a year now, the public-health message has been to wait. First we waited until it was safe to go outside. Then we waited  for vaccines to be developed, tested, and approved. Now people are being asked to wait their turn to get vaccinated; then to wait a few more weeks until they’ve received their second dose; and then two weeks more to make sure that their immune responses have fully kicked in. And finally, when all that waiting is done, we’re supposed to wait for “some time” more?

The experts urging patience are, of course, correct. There are myriad details of physiology and molecular immunology that remain to be understood, and we do not know how quickly transmission rates will drop as large numbers of people get vaccinated. At an individual level, though, the proper advice on what constitutes safe behavior does not depend on any scientific study whose results are pending. It depends on what’s happening in the world around us.


As you’ve heard ad nauseam by now, the SARS-CoV-2 vaccines were developed at record speed. They were created in the heat of an emergency, while thousands of people were dying every day, as a way to stop the carnage. They are proving remarkably effective at this.

The vaccines were never expected to block infection by the virus altogether, explains Stephen Thomas, the chief of the infectious-disease division at SUNY Upstate and the coordinating principal investigator for the Phase 3 Pfizer-BioNTech vaccine clinical trial. “I don’t really think that’s feasible or plausible,” he told me. Most vaccines work by training the body to prevent a virus from replicating to such a degree that a person gets sick. They don’t typically prevent a person from getting infected; they simply make that infection less consequential, and enable the body to clear it more quickly.

If a vaccine could reliably prevent future infections from ever taking hold, it would provide what’s known as “sterilizing immunity,” Syra Madad, an epidemiologist at NYC Health + Hospitals, told me. This is an uncommon occurrence. The measles vaccine is often cited as an exception, but she says that there is no reason to expect the COVID-19 vaccines to fall into this rare category.

Indeed, there is no obvious mechanism by which they could. “To generate sterilizing immunity in a mucosal space using a vaccine that’s injected into your muscle is extremely difficult,” Angela Rasmussen, a virologist at Georgetown University, told me. She said that early evidence in rhesus macaques has suggested that the AstraZeneca vaccine could provide sterilizing protection, but only when administered as a nasal spray. Other researchers have begun to work on nasally delivered vaccines that could theoretically serve to coat our mucous membranes with antiviral armor, though there is no certainty that this approach would be effective at preventing severe disease.

So it’s safe to assume that the current batch of COVID-19 vaccines won’t stop viral transmission outright. But it’s also safe to assume that they will reduce that transmission to some extent, because they impede viral replication. “It is highly plausible that a vaccine that prevents disease by lowering the amount of virus in a person could also lower that person’s ability to infect others through the same mechanism,” Thomas said. The tricky part is determining the degree to which this happens.

“No definitive clinical trial can give you this evidence,” Rasmussen said. The trials were really designed for speed and safety, so the researchers were most concerned with looking for symptomatic COVID-19 or adverse reactions, not asymptomatic infections. To know how often vaccinated people were asymptomatically carrying the virus, researchers would have had to test each of the tens of thousands of people in their clinical trials as frequently as possible.

Some ongoing trials have taken to swabbing the noses of vaccinated people occasionally, and this could add insight into how common it is for people to carry the virus after vaccination. Early evidence from Johnson & Johnson’s clinical trial, for example, suggests a significant reduction in transmission after vaccination, though this remains to be verified. Still, occasional testing is bound to miss cases of infection, and finding some virus in some noses doesn’t tell us how infectious the owners of those noses might be—or whether they’re infectious at all.

The only way to answer this question for certain would be to run a “challenge” trial in which vaccinated and unvaccinated people were deliberately exposed to the virus under similar conditions, and then tested to see what percentage of them got infected. That’s just step one. Then the vaccinated-but-infected people would need to hang out with a bunch of unvaccinated people to see if they got infected, and at what rate. This is not going to happen. Challenge trials are ethical minefields in normal times; at this point, any study that involves withholding a vaccine from a control group would be difficult to justify.

More trial data are expected over the next few months, and these may help narrow our uncertainty. It would certainly be useful to get a better sense of whether the risk of catching COVID-19 from your grandmother, for example, drops by something like 90 percent once she’s vaccinated, or whether it’s closer to 10 percent—but that number isn’t going to be exact, and it won’t be static, either. Even if we could somehow run the sort of challenge trial described above, whatever value it produced could change as new variants of the virus take hold, and it might well vary across regions with different patterns of prior infection, behavioral norms, local weather, and other variables we don’t even know to look for.


All of this is academic. Whatever trial data might arrive in the coming months won’t change the practical advice: As long as a lot of virus is still circulating in a community and many people remain unvaccinated, the mere fact that some have protection will not mean that it’s  responsible for them to forgo precautions and do whatever they like.

A different kind of data, though, will offer that reassurance and certainty. This is what we’re really waiting on. “We will absolutely get to a point when we can say that vaccinated people don’t need to wear masks,” Madad said, but that will be driven largely by changes in the number of cases, and in the vaccination rate. The sooner we can drive the former down and the latter up, the sooner normalcy returns. As populations draw closer to herd immunity, the chance of a vaccinated person both carrying the virus and coming into close contact with a nonimmune person will become so low that the guidelines will change.

But as long as the virus remains omnipresent, the risk of getting infected (and transmitting) the virus after being vaccinated remains too high to countenance. This message need not be seen as pessimistic or ambiguous. It tells us very clearly that our social lives can resume, but only when the whole community is ready. The turning point does not arrive for individuals, one by one, as soon as they’ve been vaccinated; it comes for all of us at once, when a population becomes immune. How quickly this occurs depends on how reliably those vaccines reduce transmission. But it will primarily be a function of how quickly people get access to vaccines, how much immunity already exists in a population, and how much attention is given to basic preventive measures that should never go away, such as well-ventilated workspaces and responsible sick-leave policies. Much of this is in our hands now. We are not waiting on a clinical study; we are waiting on one another.

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