Medical Health Cluster

18 julio, 2022

Is BA.5 the ‘Reinfection Wave’?

Well, here we go again. Once more, the ever-changing coronavirus behind COVID-19 is assaulting the United States in a new guise—BA.5, an offshoot of the Omicron variant that devastated the most recent winter. The new variant is spreading quickly, likely because it snakes past some of the immune defenses acquired by vaccinated people, or those infected by earlier variants. Those who have managed to avoid the virus for close to three years will find it a little harder to continue that streak, and some who recently caught COVID are getting it again. “People shouldn’t be surprised if they get infected, and they shouldn’t be surprised if it’s pretty unpleasant,” Stephen Goldstein, a virologist at the University of Utah, told me.

That doesn’t mean we’re about to have a surge on the scale of what we saw last winter, or that BA.5 (and its close cousin BA.4) will set us back to immunological square one. Goldstein told me that he takes “some level of comfort” in the knowledge that, based on how other countries have fared against BA.5, vaccines are still keeping a lot of people out of hospitals, intensive-care units, and morgues. The new variant is not an apocalyptic menace.

But it can’t be ignored, either. Infections (and reinfections) still matter, and by increasing both, BA.5 is extending and deepening the pandemic’s ongoing burden. “We will not prevent all transmission—that is not the goal—but we have to reduce the spread,” Maria Van Kerkhove, an infectious-disease epidemiologist at the World Health Organization, told me. “It’s not over, and we are playing with fire by letting this virus circulate at such intense levels.”

The age of Omicron began shortly after Thanksgiving, as the new variant swept through the U.S., ousting its predecessor, Delta. That initial version of Omicron, now known as BA.1, was just the first of a mini-dynasty of related variants that have since competed against one another in a grim game of succession. BA.2 took over from BA.1, and caused a surge in the spring. BA.4 and BA.5 are spreading even more quickly: First detected in South Africa in January and February, they have since displaced BA.2 all over the world, leading to surges in both cases and hospitalizations. In the U.S., BA.5 now accounts for about 54 percent of all COVID infections, and BA.4, about another 17 percent. (Most of this article will deal with BA.5 alone because it already seems to be outcompeting its cousin.) Hospitalizations have risen to their highest level since March.

You might assume that a new variant gains dominance by being inherently more transmissible than its forerunners. Using that logic, buttressed by some back-of-the-envelope calculations, some commentators have claimed that BA.5 is as transmissible as measles, making it among the most contagious viral diseases in history. But those calculations are “fully wrong,” Trevor Bedford, a virologist at the Fred Hutchinson Cancer Research Center, told me. Variants can spread rapidly without being any better at finding new hosts, as long as they’re better at slipping past those hosts’ immune defenses. That property—immune evasion—likely enabled BA.1 to oust Delta last winter. It might also explain why BA.5 is rising now.

When people are vaccinated or infected, they develop antibodies that can neutralize the coronavirus by sticking to its spike proteins—the studs on its surface that the pathogen uses to recognize and infect our cells. But BA.4 and BA.5 have several mutations that change the shape of their spikes, which, like swords that no longer fit their sheaths, are now unrecognizable to many antibodies that would have disarmed older variants. That’s why, as many studies have now consistently shown, antibodies from triple-vaccinated people, or people who had breakthrough infections with earlier variants, are three to four times less potent at neutralizing BA.4 or BA.5 than BA.1 or BA.2. This means that most people are now less protected against infection than they were two months ago—and that some people who got COVID very recently are getting reinfected now. “I hear from a lot of people who just had COVID in February, March, or April and now have it again,” Anne Hahn, a virologist and immunologist at Yale, told me.

As my colleague Katherine J. Wu has reported, the consequences of reinfections are still unclear. It’s unlikely that each subsequent bout of COVID is worse for an individual than the previous one; this idea has proliferated because of a recent preprint, which really only showed that getting reinfected is worse than not being reinfected. Nor should people worry that, as one viral news article recently suggested, “it is now possible to be reinfected with one of Omicron’s variants every two to three weeks.” BA.5 is different from its forebears but not from itself; although someone could catch the new variant despite having recently had COVID, they’d be very unlikely to get infected again in the near future.

Though previous immunity has been dialed down a few notches, since BA.5 showed up, it hasn’t disappeared entirely. “We’re seeing that new infections are disproportionately people who haven’t been infected before,” Meaghan Kall, an epidemiologist at the U.K. Health Security Agency, told me. About half of those in England who have been infected in the current wave are first-timers, even though they account for just 15 percent of the country’s population. This clearly shows that although reinfections are a serious problem, the population still has some protection against catching even BA.5.

The degree to which the new variant escapes immunity is also a shadow of what we saw last winter, when Omicron first arrived. For comparison, antibodies in vaccinated people were 20 to 40 times worse at neutralizing BA.1 than the original coronavirus. BA.5 reduces their efficiency threefold again—a small gain of sneakiness on top of its predecessor’s dramatic flair for infiltration. “BA.5 is doing what Omicron does but with a marginally more effective immune evasion,” Kall told me. “I don’t believe that it represents a massive paradigm shift.”

Why, then, does it feel like we’re in a reinfection wave right now, with anecdotal reports being prominent in a way they weren’t seven months ago? It’s because Omicron completely changed our baseline. Before its arrival, only a third of Americans had ever experienced COVID. By the end of February, almost 60 percent had. We’re hearing more about reinfections now in part because the number of people who could possibly be reinfected has doubled.

BA.5’s impact on society will differ greatly around the world. Both South Africa and the U.K. have experienced only small rises in hospitalizations and deaths despite surging BA.5 cases, showing that “protection from vaccines against severe disease and death is still really strong,” Kall said. Portugal hasn’t been so lucky, with deaths climbing to levels that approach those of the first Omicron surge. These differences should be expected. On top of their demographic differences, countries are now complicated patchworks of immunity; citizens vary in how many times they’ve been infected or vaccinated, which vaccines they’ve gotten, and which variants they’ve encountered.

Still, it’s possible to predict what might happen as BA.5 ascends in the U.S. by looking at its effective reproduction number, or Rt—the average number of people whom each infected person then infects. The original version of Omicron, BA.1, “came in really hot,” Trevor Bedford told me. With an initial Rt of between 3 and 3.5, he estimates that it infected almost half the country in a few months, including 3 million to 4 million people a day at its peak. (These numbers are higher than the official counts, which have always been underestimates.) BA.2 was less ferocious: With an initial Rt of 1.6, it infected about one in 10 Americans in the spring, and peaked at roughly 500,000 daily infections. BA.4 and BA.5 have a slightly higher Rt but should “mostly mirror the BA.2 epidemic,” Bedford told me. It might not look that way on recent charts of new cases, where the close overlap between BA.4/BA.5’s rise and BA.2’s decline creates “the illusion of a plateau,” Bedford said, but the U.S. is nonetheless experiencing its third Omicron surge. He expects BA.5 to infect 10 to 15 percent of Americans over the next few months.

Of course, it doesn’t have to. The Biden administration, other political leaders, and many media figures have promoted laxer COVID policies, on the grounds that vaccines are still reducing the risk of death and hospitalization. But this stance is foolish for several reasons.

Even if the infection-fatality ratio for COVID—the risk that an infected person will die—falls to the level of seasonal flu, rare events stack up when the virus is allowed to spread unchecked. Bedford estimates that in such a scenario, COVID could still plausibly kill 100,000 Americans every year, “which is a lot!” he said. “It’s not like in the peak of the pandemic, but it’s a major health burden.” That burden is still mainly borne by the elderly; low-income workers; Black, Latino, and Indigenous Americans; and immunocompromised people. The entire Omicron dynasty may well have arisen from chronic infections in immunocompromised patients, in whose bodies the virus can evolve more rapidly, which suggests a self-interested case for preventing infections in this group, along with the more obvious moral rationale.

Death isn’t the only outcome that matters, either. Even without sending people to the hospital, infections can lead to the persistent and in many cases disabling symptoms of long COVID—a risk that vaccines seem to lower but not fully avert. “I’m not worried about dying from COVID, but I’m personally cautious because of worries about long COVID,” Bedford told me. “I’m not a hermit, but I’m taking mitigation measures to try not to get sick.” And even “mild” infections can still be awful. Dan Barouch, an infectious-disease specialist at Harvard Medical School, told me that friends and colleagues have “felt pretty terrible at home, sometimes for weeks, but weren’t sick enough to go to the ICU and get intubated. There’s a lot of time missed from school and work.” Waves of sick employees are still disrupting sectors that were already reeling from the Great Resignation—including the health-care system. An exodus of experienced colleagues and untenable levels of burnout have trapped health-care workers in a chronic state of crisis, which persists even when hospitalization numbers are low, and deepens whenever the numbers climb.

Preventing infections still matters, and vaccines are still a crucial means of doing so. After a frustrating delay, Omicron-specific boosters are on the way, and the FDA has recommended that these include components of BA.4 and BA.5. The updated shots won’t be ready until October at the earliest, by which time new variants could have arisen. But “even if we don’t nail the match exactly,” Goldstein said, these boosters should expand people’s antibody repertoire, leaving them better defended against not just the Omicron dynasty but also other variants that could follow. Still, “it’s important not to overpromise the efficacy of Omicron-specific boosters,” Barouch said. In terms of preventing infections, clinical data suggest that they’ll be modestly better than current vaccines, but not substantially so. And even if we get the long-desired shots that protect against all coronaviruses, it may be difficult to persuade Americans to get them.

Vaccines were never going to end the pandemic on their own. They needed to be complemented by other protective measures such as masks, better ventilation, rapid tests, and social support like paid sick leave, which were either insufficiently deployed or rolled back. And with stalled COVID funding jeopardizing supplies of tests, treatments, and vaccines, the U.S. will continue its long streak of being underprepared for new variants.

Consider BA.2.75, another member of the Omicron family, which has many spike mutations not seen in its cousins. In India, where that subvariant was first identified, it seems to be spreading at a rate double that of BA.5 and comparable to that of BA.1, Bedford told me. This worrying picture is based on a small number of samples, and BA.2.75’s actual pace may be slower. It may also struggle to spread in places like the U.S., where BA.5 already rules. But no matter what happens, this round of variants won’t be the last we contend with.

The belief that viruses inevitably evolve into milder versions is a myth: Such futures are possible but in no way guaranteed. The coronavirus could yet evolve into more severe variants, although vaccines would still be expected to blunt their sting. It could become even more contagious, although the traits that would give it a speed boost, such as higher viral loads or tighter attachments to human cells, can’t ratchet up forever. “It’s already super-transmissible, and there’s not much to gain there,” Anne Hahn told me.

Immune evasion is another matter. The virus is likely now locked with the human immune system in a perpetual evolutionary arms race. A variant emerges to circumvent our existing immunity, then vaccines and infections gradually rebuild our defenses … until another variant emerges. This is exactly what happens with flu, but the coronavirus seems to be changing even more quickly. The big uncertainty is whether the next variants will erode immunity to the small degrees that scientists expect (as BA.5 is doing) or whether they’ll do something dramatic and unexpected (as BA.1 did). This is what “living with COVID” means—a continual cat-and-mouse game that we can choose to play seriously or repeatedly forfeit.

The stakes of that game depend on a very simple question: Should we still care about preventing infections? If the answer is “not so much,” which is the implicit and sometimes explicit posture that America’s leaders have adopted, then BA.5 changes little. But if the answer is “yes,” as I and most of the experts I talk to still believe, then BA.5 is a problem.

Créditos: Comité científico Covid

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