Vaccine questions on booster shots, kids, mandates, and efficacy, answered.

Vaccines—they were supposed to be the sword that slayed the pandemic. But the excitement of this past spring has given way to a fair amount of disappointment, and we’re now confronted with new, unsettling questions: Are the vaccines still effective against Delta? Will we need boosters forever? Will kids ever get their shots? The core question at the heart of these remains the one we’ve had all pandemic: When will this all be over? Over the months that question has slowly morphed into a more cautious will this ever be over? But the situation is actually—finally—changing slightly as things like Biden’s vaccine mandate for employees takes effect, and kids get closer and closer to being able to be vaccinated. In this strange moment where it feels like the hope of vaccines is evaporating, it’s important not to lose sight of the long game. There will be setbacks, and we’ll never return to 2019, but with vaccines we’re soon going to be living in a much safer, much less disruptive world.

I’m reading all this stuff about the vaccines losing effectiveness. What’s really going on?

A lot less has changed than you might think. It’s true that breakthrough cases are more common than had been hoped for based on Pfizer-BioNTech’s and Moderna’s original clinical studies—where the vaccines prevented roughly an astonishing 95 percent of symptomatic infections. Now, it’s clear that the vaccine’s power to prevent symptomatic infections isn’t quite that strong. In the messy real world, it’s surprisingly hard to pin down the exact percentage due to a complex mix of factors involving waning immunity, increased socialization, and new strains such as Delta. So we don’t really know how effective the vaccines are at preventing symptomatic infection, and estimates vary over a maddeningly wide range, from 41 percent to 88 percent.

But even with this news, it’s important to remember that it was never likely that COVID vaccines would grant god-like immunity in which viruses perish upon contact with the glowing skin of the vaccinated. Rather, a vaccine is deemed suitable for us mortals if it prevents severe disease and death. And the data here is much more certain. Data published by the CDC last week found vaccines reduce the risk of hospitalizations by around 85 percent. Additional data from Germany last week showed a reduced risk of hospitalization by 94 percent and death by 91 percent in people over 60, according to the Wall Street Journal. A recent study from the UK found that a vaccinated person has a 1 in 500,000 chance of dying from COVID, and 77 percent of breakthrough deaths were in people categorized as “clinically extremely vulnerable.” As for long COVID, the data here is sparse, but an encouraging study published a few weeks ago suggested that vaccines might halve the risk of developing the condition. So even though minor breakthrough cases can be miserable, and severe breakthrough cases can happen, the important takeaway is still basically the same: If you’re vaccinated, you’re much less likely to end up in the hospital or die. In a pandemic, that qualifies as great news.

OK, wait, but didn’t Delta change things?

Yes and no. The good news is many recently released studies were conducted while Delta was the dominant strain, so the statistics probably hold for now. The bad news is because Delta is more transmissible, there are more cases overall, and each case may be more contagious, so you are more likely to be exposed to an infectious amount of virus. In other words, more sick people means more chances of crossing paths with a sick person. So Delta does change the overall risk to a vaccinated person—not so much because Delta defangs the vaccines, but because its circulation raises a vaccinated person’s risk of infection.

That’s good to know. I heard Delta is petering out anyway.

In India and the UK, Delta’s surge had a surprisingly abrupt end. The reasons for the precipitous decline in cases aren’t fully understood. In the U.S., Delta infections already seem to be peaking in some places. However, a few factors could reverse the decline. Specifically, we’re heading into a school year, we’re heading into the season where people spend more time indoors, many places have lifted mask mandates, and many places continue to have low vaccination rates. So it’s possible we’re through the worse of Delta. Or not! We’ll have to give an optimistic shrug to this one.

But what about the next variant? I don’t have the energy to make it all the way through the Greek alphabet.

The more SARS-CoV-2 circulates, the more it will mutate. Most mutations don’t change anything, and some are even harmful to the virus itself. But on rare occasions, mutations deal the virus a winning hand. Vaccines work by teaching the body to amplify antibodies that neutralize the coronavirus’s threat. Because antibodies only work when they can physically glom on to the virus, a mutation that changes the part of the virus where antibodies attach could, in principle, decrease the effectiveness of a vaccine. But the immune system has a few tricks up its sleeve: it doesn’t just generate one kind of antibody to fight off the virus. Several different antibodies might each be tailored for different parts of the virus. So even if the viral mutation lets the pathogen dodge one type of antibody, there are many others to slow it down. And apart from antibodies, other immune cells such as T cells—which dispatch of any of our own cells that become infected—can act as a backstop to prevent the virus from wreaking serious havoc. So it’s unlikely that a virus will evolve to evade every immunological defense the vaccine creates. In fact, the Alpha variant circulating in the U.S. this spring carried worrisome antibody-evading mutations, yet did not seem to have an appreciable effect on vaccine evasion.

Yeah, but I heard some pretty important people say vaccine evasion is likely…

Fair enough. The CDC director Rochelle Walensky said we’re “just a few mutations” away from a vaccine-evading virus. And the Pfizer CEO Albert Bourla says vaccine evasion is “likely.” But these comments need a little context. Right now, there are enough uninfected and unvaccinated people in the world that the current situation favors more transmissible variants over vaccine-evading variants—hence Delta’s devastating sweep. At some point, however, as enough people gain immunity—either naturally, via vaccines, or both—contagiousness alone won’t be enough to drive viral spread, and the virus will evolve better mechanisms to evade immunity. However, some speculate the virus may also have its molecular hands tied. This is a little technical, but let me try to explain why: The protein the virus uses to infiltrate cells—the spike protein—is the same one targeted by the vaccine-induced immunity. So any changes the virus makes to the spike protein that help the pathogen evade detection may also disarm the pathogen itself, by hobbling its ability to infiltrate cells.

The shorter, less technical answer? A variant that significantly evades vaccines may be on the horizon, but it’s probably not imminent. And if one is detected, the good news is that an updated vaccine could be ready in about 3 months.

OK, well surely the booster shots will help subdue the virus, right? Even if they’re not recommended for healthy people under 65?

There’s surprisingly little solid evidence that they’ll help curb the pandemic, which is part of why the FDA panel limited its recommendation in this way. The boosters will probably reduce breakthrough infections by temporarily upping antibody levels. These higher levels could help prevent more severe infections simply because fewer people will get infected overall. And in turn, fewer infections could mean less community spread. As logical as this sounds, however, some are skeptical that an antibody top-off in young, healthy immune systems would have a durable effect on community transmission. The evidence is also inconclusive as to whether, for most vaccinated people, boosters meaningfully decrease the chances of severe disease and death—which were pretty low to begin with. And boosters could also increase the chance of rare but troublesome vaccine side effects, but this too, isn’t known. So although the boosters may temporarily provide, well, a boost, it’s not a slam dunk that they’re going to fundamentally change the situation.

It doesn’t sound to me like boosters have much of a downside. Why are experts arguing against them?

Many scientists are upset with what they view to be a data-light decision motivated more by politics. By announcing boosters would become widely available soon, the Biden administration subverted the usual process of letting agencies such as the Food and Drug Administration weigh in—causing two top FDA officials to resign over what they saw as the administration’s strong-arm tactic. But setting these scientific and political questions aside, there’s also an important moral dimension. With only 2 percent of people in low-income countries vaccinated, many, including the World Health Organization, are urging wealthier countries to forgo widespread booster shots—which may help prevent breakthrough infections but only offer marginal benefit for severe disease—and instead route those crucial doses to less vaccinated countries where they will save more lives. There’s also a selfish benefit to the wealthier countries: As fewer people get infected globally, the virus will have fewer chances to mutate into something more evasive or infectious or deadly. In theory, it shouldn’t have to be an either/or, but we live in reality. There’s concern that rather than spend time and energy hammering out the complex logistics of globally distributing vaccines, wealthier countries will instead focus on the logistics of booster programs within their borders. So, paradoxically, booster programs for wealthy countries aren’t only morally problematic, but as a practical matter could actually make things worse as the virus keeps circulating and mutating around the globe (Exhibit A: Delta).

OK, but aside from boosters, Biden just announced some new vaccine mandates. How much could that help?

Most of us who have jobs need to keep them, which means the recent spate of vaccine mandates will likely increase vaccination rates more than any public health messaging campaign. Biden has required vaccination for all federal workers, and required that employers with more than 100 employees vaccinate their workforce. Many universities are requiring students to show proof of vaccination before enrolling in fall classes, and the Los Angeles school district was the first to require that staff and students over age 12 be vaccinated. America’s patchwork of mandates easily apply to more than 100 million adults (though it’s not clear how many of those adults have already been vaccinated). Add to that the authorization of the vaccine for the 48 million kids under 12 and the upcoming months could see a lot of newly immunized Americans—which almost certainly slow down the pandemic here.

What exactly is that timeline for the children’s vaccine?

Dr. Anthony Fauci recently told the New York Times the Pfizer’s data on kids would be released by early October at the latest. If the FDA greenlights the authorization, he said, then the Pfizer vaccine could be ready towards the end of fall or beginning of winter—although Reuters reports the agency could authorize the vaccine for kids age 5-11 as early as mid- to late-October. At an industry conference, according to The Hill, Pfizer CFO Frank D’Amelio said the company plans to apply for authorization in kids under 5 about a month later, in early November, meaning FDA authorization could come 3-6 weeks later, in time for the holidays.

Ugh, just tell me when this is going to end.

I wish I knew! The trauma of the past year and a half has been profound, and for much of the world, the worst has yet to come. But it’s worth revisiting what “end” means. Even if the mandates and the pediatric authorizations push America past the threshold to attain herd immunity—that moment when enough people are immune that new outbreaks fizzle rather than sweep the nation—herd immunity may not quite be the Shangri-La people imagine it to be. Herd immunity doesn’t mean SARS-CoV-2 vanishes from the face of the earth. It doesn’t mean new outbreaks won’t occur. It doesn’t mean you won’t be exposed to the virus—in fact, you almost certainly will no matter what. As deflating as it might seem, the reality is that you can’t just wait this one out—and that realization could also be liberating.

For those who have the luxury of considering such things, the question isn’t “How do I avoid the virus completely?” but “When is it less risky to get exposed?” The answer to that still depends on whether you’re vaccinated yet, whether the case rates are low in your area, and whether your local healthcare system isn’t overwhelmed. But as these things continue to trend favorably—thanks in large part to vaccination—it’s going to get less and less risky out there for everyone.



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