A Blog by Jonathan Low

 

Dec 18, 2021

Why We May Never Really Be Fully Vaccinated From Here On

The early hope for one vaccine to rule them all appears increasingly and frustratingly out of reach. 

But just as for many other diseases with which mankind has learned how to coexist  it may be that there is no such thing as 'fully vaccinated.' Adequately vaccinated based on what we know now may be as good as it gets. JL 

Katherine Wu reports in The Atlantic:

For nearly a year now, being fully vaccinated against COVID-19 is a ticket for a slate of liberties—a pass to travel without testing and skip post-exposure quarantine and in parts of the country, a license to enter restaurants, gyms, and bars. For many employees, full vaccination is now a requirement. (But) what counts as fully vaccinated during a lull in a Delta wave might be insufficient to fend off an Omicron surge. In this long fight against a fast-moving, fast-morphing virus, we may never actually, truly be fully vaccinated

For nearly a year now, the phrase fully vaccinated has carried a cachet that it never did before. Being fully vaccinated against COVID-19 is a ticket for a slate of liberties—a pass to travel without testing and skip post-exposure quarantine, per the CDC, and in many parts of the country, a license to enter restaurants, gyms, and bars. For many employees, full vaccination is now a requirement to work; for many individuals, it’s a must for any socialization at all.

Sometime in the very, very near future, that status—and the perks that come with it—could evaporate in an instant for millions of Americans. Medical experts and public-health officials have for weeks been calling for the CDC to alter the definition of fully vaccinated to include another dose. Countries such as Israel have already done it; Anthony Fauci has been gunning for the switch. As he told me this summer, “I bet you any amount of whatever” that three shots, spread out over several months, will ultimately be the “standard regimen for an mRNA vaccine.” Even the CDC told me this week that it “may change [the] definition in the future”—a line it’s never used with me before. For a cautious government agency, that’s kind of a gargantuan leap. A new floor for full vaccination, one that firmly requires what we’re now calling booster shots, is starting to look like a matter of when, not if.

The CDC has already ballooned its pool of booster-eligible people to include nearly every American who was fully vaccinated by the end of spring (or later, if they got Johnson & Johnson)—an urgent push to seriously, get boosted n-o-w, but short of an order that says “Actually, you must, or suffer the consequences.” Now might be the time to turn stern urging into a legitimate stick, as the United States collides with Omicron amid an ongoing Delta surge. (To be fair, the CDC offers no carrots to the boosted, either.) Nearly 150 million fully vaccinated Americans, 20 million of them over the age of 65, have yet to nab a booster—and they are heading into the winter with far fewer infection-fighting antibodies than they had in the spring.

A change in definition would almost certainly spur some individual action in the short term; it’s maybe the closest the CDC can get to mandating boosters without, you know, mandating boosters. But it would also invite a whole lot of mess. Millions of people would be bumped back into “partially vaccinated” purgatory. Unvaccinated people would have one more hurdle to clear to achieve CDC-sanctioned status; some could be further disincentivized from getting the necessary shots. If Fauci is correct, the amendment is inevitable, and the risks of a logistics and communications tangle are worth taking now. But some other experts aren’t so sure. “We still don’t know what the optimal vaccination schedule is,” Boghuma Kabisen Titanji, an infectious-disease physician at Emory University, told me.

And there’s still no consensus on what our COVID-19 vaccines are supposed to accomplish in the short or long term. Stamp out severe disease? Aggressively tamp down all infections, so that we can squelch viral spread? In deciding what fully vaccinated means, it would help to know “what outcomes we’re trying to prevent, and why,” Céline Gounder, an infectious-disease physician at Bellevue Hospital Center, in New York, told me. That would dictate our dosing strategies—the what, the when, the how many.

Already, in the year since our shots first rolled out and full vaccination against COVID-19 was first defined, the pandemic landscape has shifted. And in this long fight against a fast-moving, fast-morphing virus, we may never actually, truly be fully vaccinated at all. Updating the definition of fully vaccinated is a strong move—hence the push for it at all. But it’s also a reminder of the power of waiting until we’re more sure of what we want our shots to do.


None of this waffling is, to be clear, an indictment of boosters. By this point in the pandemic, it’s quite clear that adding on more shots can come with big benefits, especially now. Months have passed since many people got their shots, leaving antibody levels relatively low. And the heavily mutated Omicron can hopscotch over several of the antibodies that are left, taking hold more easily in vaccinated bodies compared with its predecessors, and perhaps transmitting more rapidly out of them. But a booster’s bump can skyrocket both the quantity and quality of frontline immune defenses, and restore much of the body’s ability to pin the coronavirus in place. Early data suggest that while two doses of an mRNA vaccine deliver kind of meh protection against Omicron infection, tacking on another dose brings the body back to a Delta-like benchmark. Omicron will still spread within vaccinated bodies, and among them. But it will do so less often with a booster. At this point, “I don’t think we can meaningfully interrupt transmission without three doses,” Saad Omer, a Yale epidemiologist, told me. Our viral opponent has clearly upped its offense, and boosters—a bolstering of defense—have never made more sense.

Looping boosters into “full vaccination,” then, could clinch the importance of these shots. “We’ve hit a tipping point,” Jason Schwartz, a vaccine-policy expert at Yale, told me. It’s become essential to “encourage and promote boosters,” and sticking stubbornly to a now-obsolete definition of fully vaccinated could undermine that effort.

A modification wouldn’t be without precedent. The measles/mumps/rubella vaccine first debuted as a single shot, but it became a double-doser in 1989 to better contain outbreaks; the chicken-pox vaccine underwent a similar tweak in 2006. But those decisions were made with years of data to back them up. With the COVID-19 vaccines, we are still figuring out how long we can expect the benefits of additional shots to last—whether they offer only a temporary return to the early defenses that the first doses conferred, or launch people to a higher, more durable level of protection. Vaccinologists typically draw a distinction between these two outcomes: Crudely, the doses in a primary series generate new immune protection, while boosters restore those defenses once they’ve started to fade. It’s not totally clear what purpose a third mRNA dose, for instance, might serve.

This is a sticking point for Paul Offit, a pediatrician and vaccine expert at the Children’s Hospital of Philadelphia, who’s long said that the main goal of COVID vaccines should be to stave off serious illness, protection he is “certain” manifests durably after two doses. (J&J, he and others told me, should also be considered a two-dose vaccine, because the second injection adds on protection that wasn’t there before.) Offit could be swayed toward updating the definition of full vaccination, he said, if clear, consistent data show that a two-dose regimen isn’t holding its ground on the severe-disease front.

Not everyone agrees. Non-severe disease can still be very debilitating, especially for those with long COVID. We’d make massive, pandemic-ending inroads if we were able to sustainably ratchet down milder infections and transmission. More doses do seem to curb those outcomes, largely by lifting antibody levels back up. If those safeguards persist at a protective level, a third vaccine dose for the mRNAs, for instance, could be the last one we get for years. In that case, making fully vaccinated synonymous with three shots makes sense.

If defenses drop quickly again, though, the United States could be saddled with a fresh slate of post-vaccination infections in a few months’ time, spurring people to line up for another round of shots. While durable protection’s possible, if the point is to keep all infections at a minimum, we almost certainly will need to dose more often than if we’re drawing the line at severe disease. Eventually the new fully vaccinated would become obsolete too. “What’s to say that in three months we won’t be in a situation where we think about changing it again?” Titanji said. Yet another round of revisions would further erode public trust.

A definitional conversion for fully vaccinated would also create logistical nightmares for freshly instated mandates that rely on the current definition—one dose of J&J, two of mRNA. In practice, an update to fully vaccinated could completely rejigger who is and isn’t compliant; workers who only just met a two-dose mandate would have to await a third shot at the six-month mark. “You already have a lot of resistance,” Gounder said. Faced with new requirements, some employers might try to do away with mandates entirely; employees might choose to call it quits.

The prospect of three required doses could also raise a barrier for people still trying to decide whether they want to get any COVID-19 shots at all. Right now, a one- or two-dose shot means waiting two to six weeks to hit full vaccination. A three-doser could balloon that to eight months, with potentially three rounds of side effects. One of the best ways to protect the world is for unvaccinated people to get vaccinated; we could quickly find ourselves in trouble if third doses get pushed at the cost of firsts. Ideally, we’d bring the entire world to three injections—perhaps more if needed. But partial vaccination is still better than none. And the more doses we buy up and urge onto the residents of wealthier countries, the harder it becomes for people around the world to get their initial series, giving the virus more places and chances to transform itself into something even more troublesome.

With all of these factors at play, experts like Grace Lee, a Stanford pediatrician and the chair of the CDC’s Advisory Committee on Immunization Practices, thinks we might be better off shifting the conversation entirely—asking whether people are “up-to-date” on their shots, rather than whether they’re fully vaccinated. Whereas fully vaccinated implies a sort of finality, and has, to some, even become shorthand for fully protected, up-to-date is more flexible and forgiving. The phrase, which is already used among health professionals when discussing vaccines, might leave more room for individual tailoring, and it accommodates the unpredictability of our circumstances. Up-to-date is also a little more agnostic on the primary-versus-booster distinction. And asking “Did you get your shot this year?” rather than “Are you fully vaccinated?” could be an especially useful framework, Lee told me, if we end up having to retool and readminister our vaccines somewhat regularly, much like we do with vaccines for the seasonal flu.

Titanji is also in favor of focusing on increments rather than end points. She gave the example of polio-eradication campaigns in sub-Saharan Africa that billed vaccines as “additional doses” in order to help people keep pace with what was happening in their communities and the environment. Relying too heavily on who’s fully vaccinated, she said, could inadvertently imply that people’s initial doses “just didn’t count,” when it’s more that “the situation has changed.”

Millions of us have been lumped into a single “fully vaccinated” category for months, based only on the number of doses we’ve received. But the fully vaccinated are not a monolith. Some are weeks out from their shots; others, many months. Some are triply dosed, others singly. Some are older, and their immune system sleepier. And to label someone “fully vaccinated” at all invites questions about what, exactly, we are fully vaccinating them against. What counts as fully vaccinated during a lull in a Delta wave might be insufficient to fend off an Omicron surge.

Jettisoning the singular “fully vaccinated” category, then, could open up room for dosing recommendations pegged to age or immune-system status, which is already done with other vaccines. People over 65 get a higher dose of the annual flu shot; the age at which someone starts their HPV vaccination series dictates whether they get two primary doses or three. With COVID-19, older individuals might need more vaccines, while younger men might need fewer, to balance the risks of a very rare heart-inflammation side effect that’s been linked to the mRNA vaccines. And some immunocompromised people need to repeat vaccines that don’t take the first time, something physicians, including Titanji, are already asking certain patients to do by getting third and fourth COVID shots. Guidelines could still shift over time too, as both host immunity and pathogen genetics continue to evolve.

In this period where the long-term outlook for our shots is fuzzy, organizations and communities can still push strongly for boosters without “making this a three-dose vaccine,” Gounder pointed out. Several sports leagues and universities, as well as New Mexico’s Department of Health, which runs the state’s vaccine-mandate program, have already started requiring additional vaccine doses—and they’re still calling them boosters. And while a change in definition might invite behavior to follow, there’s an argument for reminding ourselves of the original goals we laid out. First doses remain essential; the unvaccinated are still the ones who are most at risk. There will be nothing to boost at all if no protective foundation has yet been laid.



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