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America’s first-ever reformulated COVID-19 vaccines are coming, very ahead of schedule, and in some ways, the timing couldn’t be better. Pfizer’s version of the shot, which combines the original recipe with ingredients targeting the Omicron subvariants BA.4 and BA.5, may be available to people 12 and older as early as the week after Labor Day; Moderna’s adult-only brew seems to be on a similar track. The schedule slates the shots to debut at a time when BA.5 is still the country’s dominant coronavirus morph—and it means that, after more than a year of scrambling to catch up to SARS-CoV-2’s evolutionary capers, we might finally be getting inoculations that are well matched to the season’s circulating strains. Which is “absolutely great,” says Deepta Bhattacharya, an immunologist at the University of Arizona.

In other ways, the timing couldn’t be worse. Emergency pandemic funds have been drying up, imperiling already dwindling supplies of vaccines; with each passing week, more Americans are greeting the coronavirus with little more than a shrug. The most recent revamp of the country’s pandemic playbook has softened or stripped away the greater part of the remaining mitigation measures that stood between SARS-CoV-2 and us. Calls for staying up-to-date on COVID vaccines are one of the last nationwide measures left—which puts a lot of pressure on shot-induced immunity to combat the virus, all on its own.

Read: The pandemic’s soft closing

The nation has latched on before to the idea that shots alone can see us through. When vaccines first rolled out, Americans were assured that they’d essentially stamp out transmission, and that the immunized could take off their masks. “I thought we learned our lesson,” says Saskia Popescu, an infectious-disease epidemiologist at George Mason University. Apparently we did not. America is still stuck on the notion of what Popescu calls “vaccine absolutism.” And it rests on two very shaky assumptions, perhaps both doomed to fail: that the shots can and should sustainably block infection, and that “people will actually go and get the vaccine,” says Deshira Wallace, a public-health researcher at the University of North Carolina at Chapel Hill. As fall looms, the U.S. is now poised to expose the fatal paradox in its vaccine-only plan. At a time when the country is more reliant than ever on the power of inoculation, we’re also doing less than ever to set the shots up for success.

In terms of both content and timing, the fall shot will be one of the most important COVID vaccines offered to Americans since the initial doses. Since SARS-CoV-2 first collided with the human population nearly three years ago, it’s shape-shifted. The coronavirus is now better at infecting us and is a pretty meh match for the original shots that Pfizer, Moderna, and Johnson & Johnson produced. An updated vaccine should rejuvenate our defenses, prodding our antibody levels to soar and our B cells and T cells to relearn the virus’s visage.

That doesn’t mean the shots will offer a protective panacea. COVID vaccines, like most others, are best at staving off severe disease and death; against BA.5 and its kin, especially, that protection is likely to be durable and strong. But those same shields will be far more flimsy and ephemeral against milder cases or transmission, and can only modestly cut down the risk of long COVID. And when partnered with a compromised or elderly immune system, the shots have that much less immunological oomph. Then say a new immunity-dodging variant appears: The shots could lose even more of their strength.

Vaccine performance also depends on how and how often the shots are used. The more people take the doses, the better they will work. But no matter how hard we try, this reformulated shot “is not going to cover everyone, either because they choose not to get it or won’t be able to access it,” says Katia Bruxvoort, an epidemiologist at the University of Alabama at Birmingham. People who haven’t yet finished their primary series of COVID shots aren’t expected to be able to sign up for the BA.5 boosts—a policy that Bhattacharya thinks is a big mistake, not least because it will disadvantage anyone who seeks a first brush with vaccine protection this fall. “The better the degree of breadth right at the beginning,” he told me, the better future encounters with the virus should go. Most kids under 12 remain in that totally unvaccinated category; even those who have completed their initial round of shots won’t be eligible for the revamped recipe, at least not in this first autumn push. Among people who can immediately get the new booster, uptake will probably be meager and unbalanced. “Realistically, the boosters are going to be concentrated in the places that have been the least impacted by the pandemic” and in people who have already had at least one boost, says Anne Sosin, a public-health researcher at Dartmouth. Such widening gaps in protection will continue to offer the virus vulnerable pockets to invade.

Crummy uptake isn’t a new issue, and some of the same deterrents that have plagued rollouts from the start haven’t gone away. Vaccines are a hassle and can come with annoying side effects. And in recent months, even more obstacles have been raised. The wind-down of COVID funding is making it much harder for people without insurance or other reliable health-care access to get boosted. And after nearly three years of constant crisis slog, far fewer people fear the virus, especially now that so many Americans have caught it and survived. A year into the Biden administration’s concerted push for boosters, fewer than a third of U.S. residents have nabbed even their first additional shot. With each additional injection Americans are asked to get, participation drops off—a trend experts anticipate will continue into the fall. “There’s a psychological hurdle,” says Gregory Poland, a vaccinologist at the Mayo Clinic, “that this is over and done.”

Read: New COVID vaccines will be ready this fall. America won’t be.

The reality that most Americans are living in simply doesn’t square with an urgent call for boosts—which speaks to the “increasing incoherence in our response,” Sosin told me. The nation’s leaders have vanished mask mandates and quarantine recommendations, and shortened isolation stints; they’ve given up on telling schools, universities, and offices to test regularly. People have been repeatedly told not to fear the virus or its potentially lethal threat. And yet the biggest sell for vaccines has somehow become an individualistic, hyper-medicalized call to action—another opportunity to slash one’s chances at severe disease and death. The U.S. needs people to take this vaccine because it has nothing else. But its residents are unlikely to take it, because they’re not doing anything else.

If all goes as planned, COVID tests, treatments, and vaccines will be commercialized by 2023—making these fall shots perhaps the last free boosters we’ll get. And yet, officials have neither a new strategy for buoying vaccine uptake nor the ammunition for clear messaging on how well the shots will work. In service of speeding up the availability of the BA.5-focused shots, federal regulators are planning to green-light the new formulation based on antibody data from mice. (Both Pfizer and Moderna have human studies planned or under way, but results aren’t expected to be ready until after the rollout begins.) The reliance on animal experiments isn’t necessarily concerning, Bhattacharya told me; the approval protocol for annual flu shots doesn’t require massive human clinical trials either. But the shortcut does introduce a snag: “We know nothing yet about the efficacy or effectiveness of these Omicron-focused vaccines,” Poland said. Researchers can’t be sure of the degree to which the shots will improve upon the original recipe. And public-health officials won’t be able to leverage the concrete, comforting numbers that have been attached to nearly every other shot that’s been doled out. Instead, communications will hinge on “how much trust you have in the information you’re getting from the government,” UNC’s Wallace told me. “And that is very tricky right now.”

Shots, to be abundantly clear, are essential to building up a properly defensive anti-COVID wall. But they are not by themselves sufficient to keep invaders out. Like bricks stacked without a foundation or mortar, they will slip and slide and crumble. Nor is a wall with too few bricks likely to succeed: If the goal is to preemptively quell a winter case surge, “a booster that will have maybe 30 to 40 percent uptake is not something we can expect to have a huge population-level impact,” Bhattacharya told me.

Read: Vaccines are still mostly blocking severe disease

All of that bodes poorly for the coming fall and winter, a time when respiratory viruses thrive and people throng indoors. The nation could see yet another round of “incredibly high surges,” says Jessica Malaty Rivera, a senior adviser at the Pandemic Prevention Institute, further sapping supplies of underutilized or tough-to-access tools such as tests and treatments, and straining a health-care system that’s already on the brink. Cases of long COVID will continue to appear; sick people will continue to miss work and school. And “God forbid we get another variant” that’s even more severe, George Mason’s Popescu told me, further overwhelming the few defenses we have.

Pinning all of America’s hopes on vaccines this fall, experts told me, may have ripple effects on our future COVID autumns too. Asked to counter the virus alone, the injections will falter; they will look less appealing, driving uptake further down. If this fall is meant to set a precedent for subsequent vaccination campaigns, it may unspool one of the worst scenarios of all: asking shots to do so much for us that they hardly accomplish anything at all.

In less than two weeks, you could walk out of a pharmacy with a next-generation COVID booster in your arm. Just a few days ago, the Biden administration indicated that the first updated COVID-19 vaccines would be available shortly after Labor Day to Americans 12 and older who have already had their primary series. Unlike the shots the U.S. has now, the new doses from Pfizer and Moderna will be bivalent, which means they’ll contain genetic material based both on the ancestral strain of the coronavirus and on two newer Omicron subvariants that are circulating in the U.S.

These shots’ new formulation promises some level of protection that simply hasn’t been possible with the original vaccines. “A bivalent vaccine will have some benefit for almost everybody who gets it,” Rishi Goel, an immunologist at the University of Pennsylvania, told me. “How much benefit that is, we’re still not exactly sure.” People who aren’t at high risk could end up only marginally more protected against severe outcomes, and no one thinks the shots will banish COVID infections for good. There is, however, a simple rule of thumb that nearly everyone can follow to maximize the uncertain gains from a shot: Wait three to six months from your last COVID infection or vaccination.

Put that rule into action, and it plays out a little differently, depending on your circumstances.

If you haven’t had an Omicron infection:

If you haven’t had COVID since about November 2021, the advantage of a bivalent booster over the original formula is obvious, and as long as you haven’t gotten boosted recently, there’s every reason to get the new one right away. (If you have been boosted in the past few months, your antibody levels are probably still too high for a new shot to do much for you.) Marion Pepper, an immunologist at the University of Washington, told me that Americans who have already gotten three or more doses “have probably maxed out the protective capacity” of the original shots. By contrast, the bivalent vaccines offer something new to those who have so far escaped Omicron: a lesson on the spike proteins of the BA.4 and BA.5 subvariants, which will help the immune system fight the real thing should it get into your body. “I’m just super excited to get the bivalent vaccine,” says Jenna Guthmiller, an immunologist at the University of Colorado who has not yet had COVID. “I think it’ll be really nice and ease my mind a little bit.”

Read: The pandemic’s soft closing

If you have had an Omicron infection:

Veterans of Omicron infections might still have something to gain from seeing the BA.4 and BA.5 spike proteins—especially if your goal is to avoid getting sick with COVID at all. Past a certain number of shots, boosters’ impact on your long-term protection against severe disease is unclear, Goel told me. Paul Offit, the director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told me he doesn’t plan on getting a booster at all this fall because, after three vaccine doses and an infection, “I think I’m protected against serious illness.” But if you want to stave off infection, Goel said, “the bivalent vaccines, or really any variant-containing vaccines, have real value.” That’s because formulas based on a given variant have been shown to temporarily increase your stock of antibodies that target that variant.

How long that extra-protective state lasts, or whether it’s sufficient to prevent any infection whatsoever, is still a scientific puzzle. The original boosters were shown to increase antibody levels to a peak about two weeks after the shot, then decay steadily over the following three months. We don’t know yet whether a bivalent formula will change that timeline, Goel said.

But you can still use it to estimate approximately when your protection will be at its highest. You might, for example, choose to err on the early side of that three-to-six-month timeline if you have a particularly high-risk event coming up in the next few weeks. “If all we had was the original booster and I was going to an indoor wedding or something, I think it would be reasonable to get that booster,” Pepper said.

Read: The BA.5 wave is what COVID normal looks like

If you had an Omicron infection this summer:

“You’re still riding the wave of antibodies that you generated as a result of that infection,” Guthmiller told me, so a shot won’t do much for you yet. That’s true regardless of which Omicron subvariant you might have been infected with, she said, because BA.2 infections have been shown to protect fairly well against today’s dominant strains, BA.4 and BA.5. (BA.2 became dominant in the United States back in March.) The severity of your illness doesn’t really matter either, Goel said. A higher fever and more intense cough might indicate that your immune system got extra revved up, he said, but they could just as easily mean that your body needs more help responding to the coronavirus. In either case, once a little more time has passed, getting the bivalent vaccine could help extend your body’s memory of its last COVID encounter, and keep infection at bay.

If you’re at high risk:

Certain groups of people should get any booster as soon as it’s available to them, the experts I spoke with emphasized to me: immunocompromised people, people over the age of 50 or so, and people with medical conditions that put them at high risk of severe disease. If you fall in one of these categories and haven’t received all the boosters you’re eligible for, “I wouldn’t wait for the bivalent,” Offit said. For people in these high-risk categories who have already gotten the recommended number of boosters, you should get the new one as soon as it’s available to you. (The FDA and CDC have not yet indicated whether they will recommend a waiting period between your most recent shot and the bivalent booster.) Goel recommended waiting at least a month after your most recent infection or shot, but if you’re very worried about your risk, you don’t need to stretch the delay to three months. Your body might still have extra antibodies floating around, but with no practical way to check at scale, “I’m honestly in favor of recommending boosting as a way to maximize individual benefit,” he said.

Read: America’s fall booster plan has a fatal paradox

If you want to wait and see:

Waiting is always an option if you want to know more about how the bivalent vaccines perform. The FDA and CDC are set to green-light the shots based on human data from the existing boosters and other experimental bivalent boosters that didn’t make it to market in the U.S.—plus trials on the new formula in mice. Pfizer and Moderna simply haven’t progressed very far in their human trials. While there’s no reason to suspect that the new shots won’t be safe, Offit recommended opting for the original boosters until more safety and efficacy data are available, which could be as soon as a couple of months after the rollout—as long as the vaccine makers or the government collects that information and makes it public. But Guthmiller and Goel said they weren’t concerned about the lack of human data, and the bivalent shot is almost certainly the better bet.

There is one significant reason to avoid waiting too long for the bivalent shot: It offers the greatest protection against infection from the subvariants it’s actually designed around. BA.4 and BA.5 might be with us through the fall and winter—or they might give way to a different branch of Omicron, or even a variant that’s entirely unlike Omicron. You’d certainly be better off against this new variant with a bivalent booster than no booster at all. But if you want to maximize your anti-infection shield while you have it, consider putting it up against the enemy you know.

By the time Jon Kostas was 25, he was desperate to beat his alcohol addiction. He had started drinking at age 13 and had cycled through different treatments—going to Alcoholics Anonymous meetings, taking pharmaceutical medications, and trying in-patient rehab—but nothing worked. Ever since 2015, however, when he took part in a clinical trial that combined talk therapy and psilocybin—the psychedelic active ingredient in magic mushrooms—Kostas has quit drinking. “I’m forever grateful and indebted,” he says. “This saved my life.”

A randomized clinical trial, published Aug. 24 in the journal JAMA Psychiatry, found that in combination with psychotherapy, psilocybin helped treat people’s alcohol use disorder. Analyzing a group of 93 patients with the condition—Kostas among them— for 32 weeks, researchers found that patients who had received psilocybin plus psychotherapy (48 in total) reduced their drinking by 83% within eight months of their first dose, compared to 51% among those who had received a placebo. Nearly half of people treated with psilocybin stopped drinking completely, compared to less than a quarter of those who’d only received the placebo.

“If these effects are replicated, I think this really would represent a breakthrough,” says Dr. Michael Bogenschutz, director of the New York University Langone Center for Psychedelic Medicine and the senior author of the study. “The effects seem to persist. And the effects are larger than those of any of the treatments that are currently available,” which includes methods like in-patient rehab, talk therapy, and medications.

Read More: Inside Ibogaine, One of the Most Promising and Perilous Psychedelics for Addiction

A more effective treatment for alcohol addiction could have profound, society-wide effects. About 95,000 Americans die from alcohol-related causes each year, including alcoholic liver disease and car accidents, according to the U.S. Centers for Disease Control and Prevention. A 2021 federal analysis of Americans pre-pandemic found that while about 5% of U.S. adults—about 14.1 million people—had alcohol use disorder in the last year, only 7% of them received any treatment, and just under 3% were treated with medication. Even when people receive treatment, however, approved medications such as naltrexone have been shown to only have limited effectiveness.

The new research adds the strongest evidence yet that psilocybin may be a promising treatment for substance use disorders. Another preliminary study by Bogenschutz and other researchers in 2015 found that psilocybin-assisted therapy seemed to treat alcohol addiction in a small test group of patients. And a small study published in 2014 by Bogenschutz and some of the same researchers found that psilocybin combined with talk therapy can help people stop smoking. Last year, the team received the first federal grant for a psychedelic treatment in over 50 years to expand that research with a three-year, multisite study.

Psilocybin’s effectiveness may have to do with how it affects the brain, says Bogenschutz. Research suggests that psilocybin promotes neuroplasticity, which allows people to change the way they think and behave. Researchers have also found that psilocybin helps treat depression—which often occurs alongside substance use disorder. One of the things that makes psilocybin such a promising treatment, says Bogenschutz, is that unlike medications that must be taken over and over again, psilocybin has a long-lasting, powerful effect after just a few doses. “It really suggests that we’re treating the underlying disorder, rather than simply treating the symptoms,” says Bogenschutz.

Read More: How COVID-19 Opened the Door to a New Era in Psychedelic Medicine

While the results of this study are encouraging, there’s still a long way to go before psilocybin can be used to treat a wider population. Fewer than 50 patients received psilocybin during the clinical trial, which means more research must be conducted on a larger, diverse population. Plus, the placebo used in the trial, diphenhydramine—an antihistamine—isn’t a perfect substitute for psilocybin, as psychedelic drugs produce unique hallucinogenic effects. Bogenschutz adds that people shouldn’t experiment with psilocybin outside of clinical settings, because it may be more risky in an uncontrolled environment, in part because patients’ experiences can feel extreme. For instance, some patients feel severe anxiety while under the drug’s influence.

The study also didn’t include the full range of people who could benefit from psilocybin-assisted treatment. Bogenschutz noted that on average, participants tended to have less severe drinking intensity than people who typically join clinical trials for the condition. (According to Bogenschutz, that’s likely because the trial may have appealed to people who were already coping with their disorder.) The researchers also intentionally excluded patients with other mental health disorders, such as depression, to ensure they could determine whether psilocybin-assisted therapy treats alcohol addiction, and not some other underlying condition.

However, Bogenschutz says it’s possible that patients with more severe disease might benefit even more from the treatment, especially if psilocybin can address the problems that underlie not only alcohol use disorder, but also mental-health issues like depression and anxiety, and even other kinds of substance use disorders. “People with co-occurring disorders and addictions might be an ideal population for this kind of treatment, because they might be able to benefit simultaneously for both disorders,” he says. Their hope is that “this more flexible pattern of brain function allows people to change their thoughts and behaviors in ways that allow them to be happier, healthier, people.”

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