To understand how the coronavirus keeps evolving into surprising new variants with new mutations, it helps to have some context: The virus’s genome is 30,000 letters long, which means that the number of possible mutation combinations is mind-bogglingly huge. As Jesse Bloom, a virologist at the Fred Hutchinson Cancer Research Center, told me, that number far, far exceeds the number of atoms in the known universe. Scientists try to conceptualize these possibilities in a “fitness landscape”—a hyper-dimensional space of peaks and valleys. The higher peaks the coronavirus discovers, the “fitter,” or better at infecting people, it becomes. The more the virus replicates, the more mutations it tries out, the more ground it explores, and the more peaks it may find. To predict what the coronavirus could do next, we would simply need to know the topography of the entire fitness landscape—which, maybe you’ve guessed, we do not. Not at all. Not even close. “We don’t actually know what peaks are out there. We didn’t know the Omicron peak was out there,” says Sarah Otto, an evolutionary biologist at the University of British Columbia. “We can’t really guess what more is possible.” What we can say is that the overwhelming majority of mutations will make a virus less fit (valleys) or have no effect at all (ridges), but a very small proportion will be peaks. We don’t know how high those peaks are or exactly how frequently they appear. When Delta took over the world, it seemed like it would sweep all other lineages away. “I would have for sure thought the next variant was going to come from Delta,” says Katia Koelle, a biologist at Emory University. Then Omicron popped up on a distant peak, in a direction no one had thought to look. The next variant may surprise us again. It could, by chance, become more virulent. It could become more transmissible. It will definitely alight upon new ways to escape the antibodies we’ve built up. The virus will keep finding those fitness peaks. To make predictions about viral evolution even harder, the fitness landscape is continuously being remodeled as our mix of immunity shifts through vaccination and infection by new variants. This in effect changes what it means for the virus to be fit. Some mountains will sink; some hills will uplift. Still, the virus is extremely unlikely to mutate so much that our immunity against severe infection is reset to zero. As more and more of the world gains initial immunity from vaccines or infection, that will dampen the most severe outcomes. Whether future variants will still cause huge numbers of infections will depend on how quickly the virus can keep evolving and how well our immunity holds up after repeated exposures. Unlike other pathogens that have been criss-crossing the fitness landscape in humans for a very long time, the coronavirus has only just gotten started. The coronavirus’s variants keep surprising us because its evolutionary leaps look like nothing else we’ve seen before. Omicron racked up more than 50 mutations, with more than 30 in its spike protein alone. Of the four seasonal coronaviruses that cause common colds, two accumulate only 0.3 or 0.5 adaptive mutations a year in their spike proteins. A third doesn’t seem to change much at all. The fourth is a mystery—we don’t have enough long-term data on it. Influenza is capable of big jumps through a process called reassortment, which can cause pandemics (as H1N1 did in 2009), but the seasonal flu averages just one or two changes a year in its key protein, Koelle told me. There are three possible explanations for why the evolution of SARS-CoV-2 looks so different from that of other viruses, and they are not mutually exclusive. First of all, we really haven’t looked that hard at other respiratory viruses. More than 7.5 million genomes of SARS-CoV-2 have been sequenced; just a few hundred or a few dozen for each of the four seasonal coronaviruses have been. When scientists try to reconstruct the relationship among these sequenced viruses in evolutionary trees, “the trees are so sparse,” says Sarah Cobey, a biologist at the University of Chicago. A whole suite of other viruses also cause common colds: rhinoviruses, adenoviruses, parainfluenza, respiratory syncytial virus, metapneumovirus, and so on. These, too, are poorly sampled. More than 100 types of rhinoviruses alone infect humans, but we don’t have a great understanding of how that diversity came to be or evolved over time. Second, the coronavirus could indeed be an outlier that is inherently better than other viruses at exploring its fitness landscape. “It helps to be an RNA virus”—which acquires mutations more quickly than a DNA virus—“and then it helps to be moving really fast,” Cobey told me. Measles takes, on average, 11 or 12 days between infecting one person and that person infecting another; the coronavirus takes only 1.5 to three. The more people it can infect, the more of the fitness landscape it can explore. Third, the coronavirus was a novel pathogen. Whatever intrinsic transmissibility it may have had, it was also unimpeded by immunity when it first arrived in the human population. That means SARS-CoV-2 has been able to infect a simply staggering proportion of the world in two years—far more people than older viruses are typically capable of infecting. And each time it infects someone, it copies itself billions of times. Some copies created in every infection will harbor random mutations; some mutations will even be beneficial to the virus. But these mutations can have a hard time becoming dominant in the short course of a typical COVID-19 infection. “It takes a while typically for a mutation to go from zero to even 5 to 10 percent” of viruses in an infected person, says Adam Lauring, a virologist at the University of Michigan. That person then transmits only a tiny number of virus particles to the next person, so most of that diversity gets lost. Across millions of infections, some of those mutations are passed on, and they gradually accumulate into one viral lineage. Delta seems to have evolved this way. The coronavirus’s ubiquity could have also seeded an unusual number of chronic infections all at once, which experts think are another big driver of viral evolution. In a chronic infection, over weeks and months, those beneficial viral mutations have time to become dominant and then transmit. This may be how Alpha originated. Omicron’s origins are still unknown. It may have evolved in a piecemeal fashion like Delta, but some experts think that its ancestors would have been found via sequencing if so. Two other possibilities exist: a chronic infection in someone immunocompromised or an animal reservoir that spilled back into humans. In both cases, the selection pressures within one immunocompromised patient or in an animal population are slightly different from those on a virus that is transmitting between humans. That may be what allowed the virus to cross a fitness chasm and discover a new peak in Omicron. Understanding the evolutionary forces that created Omicron can help us understand the realm of what is possible—even if it can’t tell us exactly what the next variant will look like. “With Omicron, I think we got lucky,” says Sergei Pond, an evolutionary biologist at Temple University. The set of mutations that makes the variant so good at infecting even vaccinated people just happens to also make it a little less inherently virulent. There’s no reason this will always be the case. The coronavirus’s virulence is a by-product of two other factors under more direct evolutionary pressure: how inherently transmissible it is and how good it is at evading previous immunity. How deadly it is doesn’t matter so much, because the coronavirus is usually transmitted early on in an infection, long before it ever kills its host. Across the immense fitness landscape, the coronavirus has many, many different paths to higher inherent transmissibility or immune escape. Take the example of transmissibility, Otto says. A virus could replicate very, very fast, so that patients shed high levels of it. Delta seems to do this, and it was more virulent. Or the virus could switch to replicating mostly in the nose and throat, where it might be easier to transmit, rather than deep in the lungs. Omicron seems to do this, and it is less virulent. The next variant could go either way—or it might chart an entirely new course. A version of Omicron called BA.2 is now outcompeting the classic Omicron variant in the United Kingdom and Denmark, though it’s still unclear what advantage it might have. Omicron doesn’t just have a lot of mutations; it has some really unusual ones. Thirteen of the mutations cluster in sites where scientists haven’t seen many changes before. That suggests mutations there normally make the virus less fit and get weeded out. But according to a preprint from Pond’s group, these 13 individually maladaptive changes might be adaptive when present all together. You can imagine, he told me, a virus under pressure to escape from existing antibodies. It acquires a series of mutations that make it less recognizable to antibodies but perhaps worse at entering cells. Under the slightly different selection environment inside an immunocompromised patient or an animal reservoir, the virus still might be able to linger—until it finds just the right combination of mutations to compensate for previous changes. In Omicron, this process remodeled key parts of the spike protein so that it both became less recognizable to existing antibodies and found a different strategy for entering cells. The coronavirus normally has two ways of infecting cells, either fusing directly with them or entering through a bubble. Omicron has become a specialist in the latter, which happens to work less well in lung cells than in nose and throat cells, and may explain the variant’s lower intrinsic severity. To get around the immune system, the virus ended up changing one of its most basic functions. Do other sets of mutations interact in unknown ways to change key viral functions? Almost certainly. We just don’t know what they are yet. We’ll have to wait and watch SARS-CoV-2in the years and decades to come. “If you look at human influenza or seasonal coronaviruses, they’ve been evolving in humans for a long time and they haven’t stopped evolving,” Bloom, the virologist, said. There are limits to how inherently transmissible the virus can get. Measles, the most transmissible known virus, has an R0 of 12 to 18, compared with Delta’s R0 of 5. Omicron’s R0 is still unclear, because a lot of its advantage over Delta seems to come from evading existing antibodies rather than inherent transmissibility. As the coronavirus has fewer and fewer nonimmune people to infect, though, immune evasion will become a more and more important constraint on its evolution. And here, the virus will never run out of new strategies, because what is optimal is always shifting. This Omicron wave, for example, is generating a lot of Omicron immunity as it moves through the population, which has in effect made Omicron less fit than when it emerged. “The next variant is more likely to be not Omicron, or something as antigenically distinct from Omicron as possible,” says Aris Katzourakis, a virologist at the University of Oxford. But exactly what that looks like? Perhaps we know enough now to know we shouldn’t try to predict that. from https://bit.ly/3AJePxZ Check out http://natthash.tumblr.com
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Pour one out for Delta, the SARS-CoV-2 variant that Season 3 of the pandemic seems intent on killing off. After holding star billing through the summer and fall of 2021, Delta’s spent the past several weeks getting absolutely walloped by its feistier cousin Omicron—a virus that’s adept at both blitzing in and out of airways and dodging the antibodies that vaccines and other variants raise. In late November, Delta made up essentially all the SARS-CoV-2 infections that researchers were sequencing in the United States. Now it’s a measly 0.1 percent. As for the rest? It’s an Omicron show. The global portrait’s a bit patchier, but by and large, “Delta won’t be able to compete,” Karthik Gangavarapu, a computational biologist at UCLA, told me. “My suspicion is that Omicron will take over.” It’s a fair shift from the tune many experts were singing just weeks ago, when they wondered whether Delta and Omicron might co-circulate in a vicious variant one-two punch. Katia Koelle, an evolutionary virologist at Emory University, told me she used to worry about that possibility when the world knew little about Omicron’s competitive edge, but “less so now.” Katie Gostic, an infectious-disease modeler at the University of Chicago, agrees that Delta doom is probably nigh. And if so, “good riddance,” she told me. [Read: The worst of the Omicron wave could still be coming] But Gostic and other experts are not quite ready to officially sound Delta’s death knell. As unlikely as it’s looking, a persistent, low-level Delta simmer—perhaps even a resurgence—is not off the table yet. Delta is still Top Variant in some parts of the world. Should it hold its own at any level, it will continue to pose a threat to us. After Omicron caught the world so off guard, “I would certainly not bet on Delta disappearing,” Lisa Gralinski, a coronavirologist at the University of North Carolina at Chapel Hill, told me. To be clear, Delta is being dwarfed by Omicron right now, in the United States and in many places abroad. Although the older variant is clinging on for dear life in a few pockets, its grasp will likely continue to slacken and slip under the weight of its craftier cousin. The main difference, Gangavarapu said, seems to be about how well each variant skirts some of the immune defenses laid down by vaccines and prior encounters with the virus; on this count, Delta’s an amateur, and the highly mutated Omicron is an A-list pro. Our repertoire of shots is still staving off severe disease and death caused by any version of SARS-CoV-2. But the antibodies that reliably keep Delta from colonizing vaccinated hosts struggle to get a grip on Omicron, which means more people are vulnerable to infection with the newcomer. (The experts I spoke with were less certain that Omicron is, particle for particle, inherently more transmissible than Delta; those data are hard to come by when so many of us carry a degree of immunity.) Omicron may also be reinforcing its own success. Delta-induced immunity doesn’t do a great job of protecting people from Omicron. But when Omicron infects people who have been vaccinated, it seems to shore up anti-Delta defenses too. (This effect is weaker in unvaccinated people, though, and it’s unclear how long the effects of these juice-ups last). That might mean that the more immunized people Omicron infects, the fewer hospitable hosts Delta will have. The new variants we get from here on out could continue to follow this pattern, displacing the morphs that came before them year after year after year. [Read: Omicron is forcing us to rethink mild COVID] Then again, maybe not. That this competition is blatantly favoring Omicron so far does not necessarily tell us where Delta will end up. All infections are interactions between pathogen and host, which means Delta could hold its own, or make a comeback, for a bunch of reasons that aren’t just about the virus itself. Some people could, for instance, be more biologically primed to foster a Delta infection than an Omicron one. Or Delta could exploit the vagaries of geography, taking stubborn root in an isolated population without much immunity of any kind, in which case Omicron’s advantage may be moot. Or it could find shelter in a little community where few Omicron-infected people have yet to tread—or, perhaps more concerningly, in an immunocompromised person, infected months ago, who has so far struggled to purge the virus. Variants in this way are like pickles: They have a way of sticking around past their anticipated expiration date. Even Alpha (remember Alpha?) still occasionally blips back onto the map, though recorded instances remain quite rare. These cases can be hard to catch; researchers don’t have the capacity to detect, let alone sequence, every SARS-CoV-2 infection out there. That means the proportions of variants in the genomes researchers report aren’t necessarily representative of their proportions in the wild. “The world is a very big place, and it’s all a numbers game,” Benhur Lee, a virologist at Mount Sinai’s Icahn School of Medicine, told me. And the longer Delta is able to bide its time, the more easily it might be able to engineer its own revival. As the world builds immunity to Omicron, the variant will have a harder time infecting new hosts; at the same time, the protective effects of vaccination and past infection that might have blocked Delta will wear off in people whom Omicron has not touched. [Read: Will Omicron leave most of us immune?] Even now, Delta has more than its fair share of opportunities to infect new people, replicate, and rejigger its genome. That is very much not what we want: Delta is thought to be the deadliest SARS-CoV-2 variant identified to date, and its descendants could very well preserve or even build upon its very lethal bite while picking up new tricks that bamboozle our immune systems. Those modifications wouldn’t have to happen in humans, either. Delta could seek temporary asylum in another amenable animal species and tweak its appearance before jumping back into us. That’s actually one origin hypothesis for Omicron, which traces its roots back to a 2020 branch of the SARS-CoV-2 family tree. In a “worst-case scenario,” Gostic said, Delta could transform into something capable of catching up with Omicron, and the two would tag-team. Dual circulation doesn’t just double the number of variants we have to deal with; it “leaves open the possibility for recombination,” a phenomenon in which two coronavirus flavors can swap bits of their genomes to form a nasty hybrid offspring, Ajay Sethi, an epidemiologist at the University of Wisconsin at Madison, told me. (Delta’s brutality + Omicron’s stealth = bad-news bears.) Alternatively, a daughter of Delta may totally overtake Omicron, exacting its ancestor’s sweet, sweet revenge. Or maybe the next variant that usurps the global throne will be a bizarro spawn of Alpha ... or something else entirely. In the same way that Omicron was not a descendent of Delta, the next variant we tussle with won’t necessarily sprout from Omicron. [Read: Omicron is our past pandemic mistakes on fast-forward] The landscape for Delta is shifting by the day. Already, researchers are investigating an Omicron offshoot, BA.2, that’s surging in countries such as Denmark at surprising speed; too little is known to say anything for sure about how it changes Delta’s chances. That means none of the hypothetical paths to Delta re-domination necessarily represents the most likely future. But they all remain possible, especially with a large fraction of the world’s population still unvaccinated, which means it’s worth preparing for them. We can’t guarantee what hijinks the virus will pull next. Even if Delta does vanish in short order, its legacy won’t go poof quite as quickly. During its tenure, Delta has infected countless people around the world, leaving behind debilitating illness and death. It is still tripping coronavirus tests. It is still filling hospital beds. It is still straining society’s capacity to care for the sick. A declining threat is not a nonexistent one. And until Delta is gone, truly gone, we’d be premature to bid it a full-throated adieu. from https://ift.tt/3g9BYjr Check out http://natthash.tumblr.com America’s tidal wave of Omicron infections seems to have crested, but it’s still in a bad place. Even as coronavirus cases are beginning to tick down nationwide, so many Americans have tested positive for COVID since Christmas Day that they account for a quarter of all cases recorded in the United States. Thanks to the immunity America has—through shots and prior infections—most of these people came out of it largely unscathed. And they got an immunity bump too: We’ve long known that an infection with COVID spurs the body to churn out more antibodies. While public-health officials are still urging all Americans to be cautious with so much of the virus around, guidance for people who have already recovered from COVID this winter is sorely lacking. That has left Omicron survivors to deal with a confusing question: What now? I reached out to a handful of epidemiologists, and they all agreed that getting Omicron isn’t a golden ticket to normalcy. However, the immune boost from an Omicron infection can still be paired with other precautions to safely go about many activities. Keeping a few pandemic principles in mind can help make everyday decisions a little less fraught. In an ideal world, Omicron survivors wouldn’t have to worry about getting COVID ever again. But because Omicron is still so new, it’s too early to know how well, and how long, immunity from infection will hold up against another bout with the virus, or what scientists call “reinfection.” Prior to Omicron, research suggested that immunity could begin to wane just three months after infection, though it has varied tremendously from person to person. COVID reinfections do occur: People who came down with the virus months ago, before Omicron had even been identified, don’t seem to have strong protection against this variant. (Virtually no one knows which variant they had, but if you got COVID sometime in the past month, it was very likely Omicron.) [Read: Will Omicron leave most of us immune?] Before letting their guard down, Americans who have had Omicron but aren’t yet fully vaccinated should get their shots. This is important not only because it protects you, but also because it builds up our collective immunity, protecting others in the process. Opinions vary, however, on the best time to get vaccinated after infection. Wafaa El-Sadr, an epidemiologist at Columbia University, told me in an email that once a person is recovered from Omicron, they must “get vaccinated and [a] booster dose as soon as eligible.” Others suggest waiting to optimize the immune response. Sten Vermund, an infectious-disease epidemiologist at Yale, told me that getting vaccinated three to six months after infection “might be very reasonable because that may be the time that the immune system could use a boost.” Because people who were fully vaccinated before falling sick with Omicron already have a good level of protection against severe illness, they have more flexibility in what sorts of behaviors they can safely engage in. Though an Omicron infection does lead to an immunity boost, the additional layer of protection provided by an actual booster shot can only help. “The level of COVID that we have out in the community is a level we have not seen anything like in this entire pandemic, so your best level of protection is still to get a booster,” Jodie Guest, an epidemiologist at Emory University, told me. By this logic, people who had two doses of an mRNA vaccine and a booster before getting infected have the best protection of all. “You’ve presented the immune system [with] the spike protein on four different occasions, so that’s likely to generate a very substantial immune response,” Vermund said. [Read: Should I just get Omicron over with?] Even for those with this quadruple-forged shield, resuming pre-pandemic activities in a world where transmission is still rampant can seem like a bad idea. Roughly 700,000 Americans are testing positive for COVID every day, almost three times the rate during last winter’s peak. Many Americans are returning to their pre-pandemic lives. Even so, I’m the type of person who passes a crowded restaurant and can think only of the plumes of Omicron particles that might be spewed and swallowed by all those open mouths. I want to invite my vaccinated and boosted friends over, but it makes me nervous that many of them regularly go out unmasked. The epidemiologists I talked with agreed that some basic cautions are still in order. El-Sadr recommended that everyone wear a mask indoors in public settings “across the board, for now.” This is a necessary precaution because we “don’t know the level of reinfection that may occur, and with so much Omicron everywhere, it’s just the right thing,” Guest said. (And wearing a high-quality mask, such as an N95 or KN95, is important--cloth masks don’t cut it anymore.) But the epidemiologists largely shared more relaxed views than I had anticipated. “As a person who’s vaccinated and boosted, and does not buy into the idea that everyone has to get Omicron, I am comfortable having an indoor meal at my home with a few friends who I know are also vaccinated and boosted,” Guest said. Going out to restaurants and bars requires more forethought because there’s no guarantee that others there will be vaccinated and boosted. If you really must dine indoors, the best option is to pick a restaurant with separated seating, good ventilation, and servers who wear masks. And wear a mask when walking through the restaurant and when the server comes to see you, Guest said. Making it through an Omicron infection doesn’t change the simple calculus around what sort of activities are safer than others. Going to a movie where you’re sitting in silence is less of a risk than a crowded indoor concert with thousands of attendees. “We still have our same principles: Outdoors is safer than indoors; ventilation is better than a not-ventilated space,” Guest told me. And the same precautions apply too: If you’re planning on attending a gathering, it’s a good idea to rapid-test yourself right before going, she said, especially if you’ll be coming into contact with someone who is immunocompromised and is more likely to get seriously sick from a COVID infection. The bottom line is the same as it’s always been—vaccines are really good at doing what they were designed to do, which is prevent severe illness. If you’re vaccinated and boosted, and you’ve been infected on top of that, your chances of having a serious reinfection are not high. This group, Vermund said, “can live a life free of undue fear of Omicron.” [Read: The worst of the Omicron wave could still be coming] But there isn’t a one-size-fits-all approach to post-Omicron behaviors. People take different factors into account when calculating risk, and naturally some are more comfortable with risk than others. For example, a 65-year-old who cares for an elderly parent should be more cautious than a healthy 25-year-old who lives alone. For now, while cases are still so high, we have few direct instructions—only guiding principles. A good rule of thumb for survivors is to acknowledge that going out in public increases your risk of reinfection, and take steps to minimize it. We still don’t know how likely reinfection is after Omicron. Take extra care if you’ll come into contact with people who are more vulnerable to illness than you. Know that the risk of reinfection is lower in places that permit only vaccinated people. And remember: Masking is effective and really easy to do. Most of all, try to not be fatalistic about Omicron by assuming that it will infect everyone. Preventing infection—and reinfection—is possible and well worth the effort. A mild or asymptomatic infection could spread to a more vulnerable person who might have it much worse. And every person who gets infected, Guest said, “is a place the virus can mutate.” Again, if you haven’t knowingly gotten COVID during the Omicron wave, it’s a good idea to remain cautious until cases subside. If the Omicron numbers continue to trend in the right direction in the coming weeks, negotiating what’s safe to do will gradually become easier—not just for the tens of millions of survivors, but for everyone. Hopefully, this will be the last time we’ll have to make these types of tough decisions. Omicron infected such a huge swath of people—many without even knowing it—that it may have pushed us closer to the end of COVID’s crisis mode, Vermund told me. Next winter, we could “conceivably have coronavirus more at the endemic rates of other respiratory viruses,” he said, “and that is a hope that can be made a reality if we can coax all Americans to get vaccinated and boosted.” from https://ift.tt/3nZ5GMB Check out http://natthash.tumblr.com Unfortunately, Omicron is far from done with us. More than 700,000 Americans are testing positive for COVID-19 every day, COVID hospitalizations in the United States are at a record high, and the variant is so contagious that an encounter with it can be postponed for only so long. The single best thing people can do to protect themselves is, yes, get vaccinated. And that includes booster shots. The immunity boost of that third shot is something of a game changer: CDC data have shown that booster shots significantly ratchet up protection from Omicron hospitalization, compared with two vaccine doses. In some charts of COVID deaths and hospitalizations, the number of triple-jabbed patients is so low, you have to squint to find them in the graphs. And though it’s not clear how long this extra protection will last, what makes getting boosted now even more of a no-brainer is that the added protection starts to build in just a few days—far quicker than after the first shot—meaning that even this long into the Omicron wave, third shots can help stave off COVID’s worst outcomes, as well as immunologically arm us for whatever variant comes next. And yet the rate of Americans who have received a booster shot is abysmally low. Although 87 percent of adults have received one vaccine dose, just 52 percent of eligible vaccinated adults are boosted—less than a third of the total adult population. One thing that could help is booster mandates—sticks over carrots. Mandates may be controversial, but they are effective. Even so, at least so far, we’ve seen astonishingly few companies or governments roll out booster mandates. Don’t expect many more: Last week, the Supreme Court batted down an effort by the Biden administration to mandate vaccines for large employers. Some companies, such as Starbucks, have responded by nixing the mandates they had voluntarily implemented. [Read: Fully vaccinated is about to mean something else] So what about carrots? During the initial vaccine rollout, incentives were hot: Two dozen states were sweetening the immunization pot with million-dollar lotteries, a chance to drive your car on the Talladega Superspeedway, TikTok contests for $250 gift cards, tickets to baseball games, $100,000 scholarships, hunting and fishing licenses, a pontoon boat, a free beer at a local brewery, or just $100 to spend however you wanted. But even as booster shots could help lessen the burden of Omicron and future variants, governments have largely abandoned these ambitious incentive programs. I reached out to the 24 states that offered incentives last year, and of the 15 that responded, 13 aren’t offering financial incentives for boosters. Arkansas still hands out a $20 lottery ticket to anyone who gets a shot—including a booster—while New York is offering the unboosted a chance to win free ski passes. This complacency around booster incentives is especially baffling because after a summer of lotteries and sweepstakes, we have a better sense of which programs show promise and which definitely don’t work. Incentive programs are never going to be the cohesive national strategy that gets us out of the pandemic. But they probably do still have a role to play: Unlike people who are staunchly opposed to vaccines, most of the unboosted are by definition not opposed to vaccines. Nudging them toward a third shot may be one of the lowest-hanging fruits in pandemic policy making. Slipping someone a $100 bill might seem like a roundabout way for a country to induce its residents to accept a lifesaving vaccine, but last year officials were desperate to get shots into arms. Politicians of all stripes flocked to incentive programs because they appeal to both sides of the political spectrum. On the right, incentives align with free-market ideologies that place choice in the hands of individuals. On the left, incentives are alluring because they may alleviate equity issues by removing financial barriers for low-income populations. Theoretically, incentives should work. Offering people cash to change health behaviors—whether to quit smoking or keep up with exercise--made a difference in previous studies. Cash might provide a fence-sitter justification to get vaccinated, or it might offer cover for someone whose desire for a vaccine goes against local social norms. And even though the COVID vaccines are free, they come with indirect costs, such as lost wages when taking time off from work to get a shot. [Read: Vaccine lottery tickets are sad, but also perfect] But theory is different from practice. “It was completely unprecedented for 24 states, more or less at the same time, to roll out these incentive programs,” says Kevin Volpp, the founding director of the Center for Health Incentives and Behavioral Economics at the University of Pennsylvania. In effect, it was a grand national experiment in whether financial incentives such as lotteries and cash guarantees work, so Volpp and his colleagues decided to put the numbers through the wringer. Despite the millions of dollars poured into these high-profile efforts, they found no difference in vaccination patterns between the 24 states with incentives and the 26 states without them. Their study wasn’t an anomaly. Although the lotteries and cash giveaways generated much fanfare, and governors boasted of their effectiveness, a flurry of academic studies now suggests that most large-scale financial-incentive programs had minimal impact, or were total duds. It’s not clear why the incentive programs seemed to fail, but Mireille Jacobson and Tom Chang, two economists at the University of Southern California, have some suspicions. Over the summer, they recruited 2,700 participants and randomly divided them into several groups—some were offered up to $50 in cash to get vaccinated, while others viewed public-health messages or received scheduling links that would make finding an appointment easier. The study itself took two months, but the analysis was basically ready in hours. “We could tell pretty quickly that there was no there there,” Chang told me. They found that for Donald Trump voters, the guaranteed $50 financial incentive actually decreased vaccination rates. “It’s not normal to pay someone to do something that’s good for them,” Chang said. If a vaccine is so good, the thinking goes, “then why do you have to pay people to take it?” But that’s not to say we should give up on incentives altogether—especially now that the future of mandates seems shakier than ever. Even though statewide lotteries and beer giveaways proved to be gimmicky busts, there could still be a role for better-designed incentive programs, especially those that target specific populations. Unboosted Americans are disproportionately racial minorities, members of low-income families, and undocumented immigrants—the same populations that are most likely to be exposed to the virus and miss work because of COVID. For them, the chance to win millions in a lottery does nothing if they can’t physically get themselves to a vaccination clinic or take time off work. Booster incentives might be more successful if they were deployed in a way that acknowledges the complexity of human psychology, local social context, and structural barriers. Sandrette Parker, a 47-year-old mother of three who lives in Henderson, North Carolina, told me that she faced these barriers. After a few months of hesitation, she finally decided that it was time to get her first shot. But there was a problem: She couldn’t get to a clinic. After losing her job, she said, “My choices were to pay rent, or pay my car payment.” Life without a car was tricky. “There’s no public transportation here, no city buses, and I don’t think I’ve ever seen a taxicab in this town,” she said. Parker finally found someone to take her family to the closest open vaccination site, some 50 miles away. A few months later, Parker said, she and her family tested positive for COVID. “Thankfully, we all had become fully vaccinated prior to catching COVID because I think it would have been worse.” To address logistical issues like Parker’s, Charlene Wong, the chief health-policy officer for COVID-19 at the North Carolina Department of Health and Human Services, designed a clever incentive program during the late spring. Her team offered people in undervaccinated counties $25 cash cards to get vaccinated—but it also added a twist, what Wong calls a “social incentive.” Anyone who drove someone else to receive a first dose also received a $25 cash card. “Social incentives really leverage the fact that we have networks of folks around us to influence our behaviors,” Wong said. The design worked: Vaccination rates were decreasing nearly everywhere in the country by that time, and the program slowed the decline by half at clinics with incentives compared with neighboring clinics without incentives. With boosters, “those same barriers—transportation, lost wages, child care—they aren’t going to magically disappear,” Wong said. [Read: It’s a terrible idea to deny medical care to unvaccinated people] What Wong’s study suggests is that simple quid pro quo financial incentives may not be sufficient to make vaccine access equitable. Julia Raifman, a public-health professor at Boston University, told me that “making vaccines easy to access—for example, a walk-in clinic, well advertised and nearby—and broad communications about who was at risk are likely more important than the financial incentives.” Community organizations around the country are racing to figure out what works. La Colaborativa, a Boston-area community organization, successfully increased vaccination rates in the low-income suburb of Chelsea to 92 percent by offering vaccination sign-ups at the same location people could pick up a box of free food or access social services. Our Healthy KC Eastside lifted vaccination rates in some of Kansas City, Missouri’s predominantly Black neighborhoods by 50 percent compared with the citywide average–by putting clinics in convenient locations and giving out $50 for first shots. There’s been no systematic assessment of how effective these more targeted programs have been nationwide. But even without the sort of high-quality evidence we would want, there’s a moral argument that anyone who wants a life-saving vaccine should be able to access it–particularly those from communities that could gain the most from third shots. From a strictly economic perspective, pouring money into booster incentives is a bet, but perhaps one worth taking. No matter what happens with workplace mandates going forward, millions of people, including the unemployed and retirees, won’t be covered by them. Targeting these people will cost money, but so will leaving people less protected from COVID. I asked Chang and Jacobson what they would say if the governor of California, for example, called them up tomorrow to inquire about a statewide incentive program for 2022. They both agreed that it would be pointless for first doses. “I’d say do it for boosters, though,” Chang said. Jacobson concurred. “I think there are a lot of people who are in this camp of Yeah, I’m gonna get a booster but I’m not in any rush,” she said. “And I would think those folks are probably pretty responsive” to financial incentives. After all, the whole point of nudges is that you target someone who’s kind of indifferent, and for whom a small incentive slightly lowers the burden of time, effort, or actual financial cost. For incentives to work, you need a lot of people on the fence—which is exactly the place we’re in with boosters. And yet there’s no longer the spirit of experimentation that pervaded the initial vaccine rollout, or really, it seems, much of a plan at all. We now know that dumping money into big-ticket lotteries maybe isn’t the best idea. And sure, maybe incentives aren’t the answer at all. But compared with the economic and human costs of not getting Americans boosted, is the small probability of landing a free ski pass really the best we can do? from https://ift.tt/3FWeQiX Check out http://natthash.tumblr.com For many months now, Pfizer’s COVID-19 vaccine has been slowly making its way into smaller arms in smaller doses—from teens to adolescents to elementary-school-age kids in the fall. Now it’s just the under-5 crowd left, and the word on the lips of parents raring to protect their children is still, simply, when. Somehow, no one yet seems to know. Back in September, the party line was that under-5 trial data would arrive “before the end of the year,” as Pfizer CEO Albert Bourla declared at The Atlantic Festival. Those data never appeared. Instead, the week before Christmas, Pfizer announced in a maddeningly cryptic press release that two little-kid-size doses of vaccine had failed to elicit a hefty-enough immune response in 2-, 3-, and 4-year olds in late-stage trials. (Doubly dosed kids in the six-month-to-2-year-old range, though, did produce enough antibodies to satisfy the company’s criteria.) But the company had a plan—researchers would test a third injection eight weeks after the second—and a new timeline, with data arriving in the “first half of 2022,” maybe April-ish. Add to that the few weeks the FDA typically takes to review the data submitted for emergency-use authorization, and the earliest shots for this group are still probably two or three months away. Then, this week, the White House’s chief medical adviser, Anthony Fauci, seemed to drop a mysterious bombshell: Surprise! Perhaps a trio of mini shots will be greenlit for use in kids under 5 “within the next month or so”--weeks ahead of the updated schedule. But he quickly backpedaled—that was just a hope, and absolutely not a guarantee. The predictions on when we’ll get the data, much less the shots, have ricocheted all the way back to idk I guess spring? [Read: COVID parenting has passed the point of absurdity] Amid all this chaos, Pfizer still hasn’t publicized any data from this youngest age group; if federal officials have that information, they, too, are staying mum. (I reached out to the CDC, which pointed me to the FDA, which pointed me to Pfizer, which said: “Unfortunately we are not offering any interviews on this right now.” Unfortunately indeed.) Parents who just want to know what’s happening are now, understandably, feeling pretty jerked around by all this talk of later? sooner? who knows! “The wait has been excruciating,” Risa Hoshino, a public-health pediatrician in New York City, told me. “They feel the world has moved on without them.” Families have been asking “every single day,” she said, when infant-and-toddler vaccines will finally make their public debut. Hoshino can’t give a definitive answer; outside of Pfizer and BioNTech, and perhaps the FDA, few people can even try. (Remember, no public data.) Still, several experts I spoke with this week remain optimistic that kids under 5 will get shots within the next few months. After seeing disappointing results in the original iteration of its trial, Pfizer took something of a gamble by adding one more small dose to the series for under-5s. But there may be good reason to believe that this bet, the company’s first official departure from the standard two-shot primary series, will pay off spectacularly. The company’s new kid-dosing strategy, experts told me, was likely designed to marry logistics to science—something that would fast-track the vaccine’s rollout while keeping the shots’ risk-benefit ratio ultrahigh. In some ways, vaccines are vaccines are vaccines. But tailoring them to individual populations—which each harbor different needs, risks, and vulnerabilities—is essential to doling them out right. Dosing is a balancing act: The more vaccine in each shot, the likelier that shot is to rile up the immune system—and the likelier it is to make the experience of getting the injection pretty uncomfortable. That means “we’re after the smallest dose possible that will still be as effective as possible,” says Buddy Creech, a pediatric-infectious-disease specialist at Vanderbilt University Medical Center, who’s leading a study of Moderna’s pediatric COVID vaccine. Pfizer already intentionally shrank the dose: Adults have been getting 30 micrograms of mRNA in each injection; in the under-5s, the company is trying three micrograms apiece. But the hope is still to, roughly, get “the response to the childhood vaccine to match what we see in adults,” typically measured by antibody counts, Creech told me. So if a pair of injections weren’t quite enough to get 2-to-4-year-olds there, a bonus third shot could be expected to push them over the top. “I’m hopeful,” Sallie Permar, a pediatrician, immunologist, and vaccinologist at Weill Cornell Medical Center, told me. “The only way to go, really, is up.” It helps to first consider what Pfizer’s other choices might have been. Subpar antibody levels in the blood might suggest that the vaccines couldn’t quite convince little bodies to take them seriously. One option could have involved sticking with two doses, but spacing them further apart—essentially giving the immune system more time to mull what it means to fight SARS-CoV-2. That strategy has been shown, at least in adults, to buoy the quantity, quality, and longevity of immune responses, and parts of Canada have been pursuing it for months in 5-to-11-year-old kids. Another alternative could have been to simply increase the dose, while keeping all else the same; each would deliver a sharper, and perhaps more memorable, scolding to defensive cells. Kids could then stay on the speediest possible track to sufficient protection: three weeks between doses, then another two of immunological cook time. “In a pandemic, you want to do that as fast as humanly possible,” Hoshino said. If Pfizer’s three-dose strategy pans out, the five-week timeline balloons to three months. [Read: Why are we microdosing vaccines for kids?] But revamping the two-dose strategy would have also restarted the clock on trials and meant recruiting and enrolling a new cohort of participants. A series of injections, potential side effects, and weeks of blood draws and other follow-ups are a cumbersome commitment for a person of any age, and “the hardest trials to get done are these young ones,” Permar said. “It’s never easy to ask a parent to consider more procedures, especially for toddlers, who are going to cry.” Even vaccine trials for older kids struggled to reach capacity. Tacking on a third dose, then, ends up being the most time-efficient option—not necessarily to get each individual child to the end of a vaccine series, but to obtain regulatory authorization, and to roll out first shots to the public. A two-big-dose option could also be unsavory for another reason—an increased chance of side effects, including fever, fatigue, and headaches, or perhaps something much rarer but more severe. In teenage boys and young men, mRNA vaccines like Pfizer’s and Moderna’s have been linked to cases of heart inflammation, though new results from the 5-to-11-year-old crowd suggest that younger kids may be spared. In any case, dose definitely matters: When it comes to vaccinating super-young kids, whose risk of contracting serious cases of COVID-19 remains relatively low, the shots “have to be supersafe, remarkably safe,” Permar said. “These are healthy, young children who might not be able to say, ‘I feel crummy.’” Perhaps the three-microgram dose was already producing some discomfort. (Do we know? No—again, there’s no data.) It might have been unwise, then, to go up to the next dose in size, the one for 5-to-11-year-olds—which, at 10 micrograms, is a more-than-threefold increase. Creech agrees: Any worries about shot tolerability could end up subjecting study participants to a bevy of irksome tests, and causing distress for the entire family. These concerns and more were part of the logic that motivated Pfizer to choose the three-microgram dose for the under-5s in the first place: In an early-phase study, that was the tiniest dose tested that still coaxed out decent numbers of antibodies in children as young as six months. It’s not clear why those results didn’t carry over perfectly into the company’s more recent trials. But Creech told me that if he’s going to hear deflating news from a kids’ vaccine trial, he’d rather it be about lackluster antibody levels than troubling side effects. With kids this young, “we’re going to put a little more weight on our safety foot than our effectiveness foot.” And three smaller doses could even be more effective than two slightly larger ones. Raising defenses to a threat is a costly endeavor for the body; sometimes, the immune system just needs another nudge before it decides to commit. Some vaccines in the pediatric-medicine roster are already doled out in two, three, or even five doses for that reason. Without Pfizer’s data, it’s impossible to know just how far below the desired threshold kids’ antibody levels fell after two three-microgram doses, but “I have to imagine they already weren’t too far off,” Permar told me. And because each shot should build on the last, three doses could succeed where two have failed. Waiting two months to give the third dose should “refine and mature” toddlers’ immune responses, Creech said. Their bodies will spend that limbo period studying and restudying the doses they’ve already gotten, and sharpening their SARS-CoV-2-sniping skills. Third shots can also goad the immune system into broadening its range of coronavirus-fighting tools, so that kids end up ready to duel even antibody-dodging variants such as Omicron. (And third doses, when injected after a delay, don’t seem to produce any more side effects than seconds, probably because the body gets the chance to cool down in the interim, based on studies in adults.) “Keeping the dose low and adding on a third just makes a ton of sense,” Permar said. Toddlers could even help pave the path to an initial trio of COVID shots being standard fodder for all. [Read: COVID parenting is reaching a breaking point] One smidgen of weirdness remains: why kids under 2 beat out their slightly older peers, as Pfizer reported in December. The magnitude of the difference isn’t yet known. (Imagine, if you will, what might be helpful here: data.) But sussing out this discrepancy could reveal some peculiarities about how immune systems transition from infancy to toddlerhood. Permar pointed out that kids’ immune systems are much more quick-witted than adults’: They can learn a lot from very little vaccine. (That’s why pediatric vaccines are dosed by immunological age, not weight.) Even newborn babies, whose immune systems don’t come out fully fledged, “are actually pretty ready to respond robustly to certain types of vaccines,” Permar said. The results are intriguing enough that some experts may want to explore the option of keeping infants on a two-dose Pfizer track. But Pfizer is still testing the effects of a third dose for this group, which may end up being practical in the long run, especially if it simplifies the number of injection regimens that doctors have to juggle all at once. (The company has not broken out the infant group to seek its own authorization first.) Creech told me he feels great about what he’s observing so far in Moderna’s pediatric trials, and he’s confident things on the kids’-vaccine front will take a turn for the better by early summer—if not for Pfizer’s shot, then for its similar-looking competitor. Moderna’s vaccine also comes in a two-dose series, but the injections are four weeks apart, and bigger: The company is testing 50 micrograms of mRNA in 6-to-11-year-olds, and 25 micrograms in kids 5 and younger (compared with 100 micrograms for adults). If Pfizer’s three-doser doesn’t work, Moderna could be toddlers’ vaccine dark horse. “I have wondered if this is the time Moderna will finally beat Pfizer” to the finish line, Permar told me. It may truly be neck and neck: Moderna’s expecting to report the first of its 5-and-under data in March, not far off from Pfizer’s own early-spring goal. Either way, it’ll be the data--of course--that dictate what happens next. from https://ift.tt/3Irv31j Check out http://natthash.tumblr.com Even before Omicron hit the United States in full force, most of our bodies had already wised up to SARS-CoV-2’s insidious spike—through infection, injection, or both. By the end of October 2021, some 86.2 percent of American immune systems may have glimpsed the virus’s most infamous protein, according to one estimate; now, as Omicron adds roughly 800,000 known cases to the national roster each day, the cohort of spike-zero Americans, the truly immunologically naive, is shrinking fast. Virginia Pitzer, an epidemiologist at Yale’s School of Public Health and one of the scientists who arrived at the 86.2 percent estimate, has a guess for what fraction of the U.S. population will have had some experience with the spike protein when the Omicron wave subsides: 90 to 95 percent. The close of Omicron’s crush, then, should bring the country one step closer to hitting a COVID equilibrium in which SARS-CoV-2’s still around, but disrupting our lives far less. In the most optimistic view of our future, this surge could be seen as a turning point in the country’s population-level protection. Omicron’s reach could be so comprehensive that, as some have forecasted, this wave ends up being the pandemic’s last. [Read: The worst of the Omicron wave could still be coming] But there is reason to believe that this ultra-sunny forecast won’t come to pass. “This wave will not be the last,” Shane Crotty, of the La Jolla Institute of Immunology, told me. “There are not many things that I am willing to be pretty confident about. But that’s one of them.” A new antibody-dodging variant, for one, could still show up to clobber us. And nearly everyone having some form of spike in their past isn’t as protective as it might sound. In a few months’ time, American immune systems will be better acquainted with SARS-CoV-2’s spike than they’ve ever been. But 90 to 95 percent of people exposed doesn’t translate to 90 to 95 percent protected from ever getting infected or sick again; more immune doesn’t have to mean immune enough. By the time the country exits this wave, each of our bodies will be in radically different immunological spots—some stronger, some weaker, some fresher, some staler. Chart that out by demography and geography, and the defensive matrix only gets more complex: Certain communities will have built up higher anti-COVID walls than others, which will remain relatively vulnerable. The malleability of the virus and the United States’ patchwork approach to combatting it has always meant that COVID would spread unevenly. Now the sums of those decisions will be reflected by our immunity. They’ll dictate how our next tussle with the virus unfolds—and who may have to bear the brunt of it. Collective immunity is the key to ending a pandemic. But its building blocks start with each individual. By now we know that immunity against the coronavirus isn’t binary—and while no one can yet say exactly how much more protection Person A (triple vaxxed, recently infected) might have than Person B (twice infected, once vaxxed) or Person C (once infected, never vaxxed), we have figured out some of the broad trends that can toggle susceptibility up or down. Allowing for shades of gray, a person’s current immune status hinges on “the number of exposures [to the spike protein], and time since last exposure,” John Wherry, an immunologist at the University of Pennsylvania, told me. Infections and vaccinations add protection; time erodes it away. Part of this boils down to relatively basic arithmetic. Each exposure to SARS-CoV-2’s spike protein, whether through injection or infection, can be expected to build iteratively on the quantity, quality, and durability of the body’s defenses The more intensely and more frequently the body is bothered, the more resources it will invest to fend off that same threat. While a duo of vaccines, for instance, isn’t enough to reliably guard against less severe Omicron cases, a trio of shots seems to do the trick for most. It also pays to pace encounters judiciously. Crowd the second and third too close together, for instance, and the latter’s effect may be blunted; a several-months-long wait, meanwhile, can supercharge the body’s response by allowing immune cells sufficient time to mull what they’ve learned. The contents of an exposure can matter too, though immunologists still debate the protective merits of tossing a dangerous, bona fide virus into the mix. Infections can blitz a smorgasbord of proteins from a currently circulating variant into the airway, tickling out immune defenses that in-the-arm, spike-centric vaccines don’t reliably rouse—but they can also, you know, cause COVID, and leave wildly inconsistent levels of protection behind. “It’s really not worth the risk,” Taia Wang, an immunologist at Stanford, told me. Those who already have both types of spike exposures in their history, though, seem to reap some of the relative benefits of each—the two stimuli synergize, and patch each other’s gaps. Post-vaccination Omicron infections, in particular, could awaken immune cells that didn’t respond to the original-recipe spike, broadening the range of defenders available for future fights. [Read: Should I just get Omicron over with?] Neither virus-induced immunity nor vaccine-induced immunity against infection seems to last terribly long, however. (Protection against severe disease, at least, has been quite a bit more stubborn, and some experts hold out hope that additional doses or infections might eventually get our defenses against milder cases to hold as well.) For now, people who have logged only a solo encounter with SARS-CoV-2’s spike, or are many months away from their last viral brush, can reasonably assume that they’re vulnerable to infection again. The fewer past brushes with spike, the speedier that relapse will be, too. Responses might be especially ephemeral in certain people, including older or immunocompromised individuals, whose immune systems aren’t easily tickled by vaccines. But it’s not always obvious why people respond differently to the same viruses or shots. Even within a demographic group, “some people generate really robust responses, and others just never do,” Wang told me. Projections based on a vaccine dosing schedule, or someone’s infection history, aren’t a surefire bet. All of this underlies, then, the massive disconnect between previously exposed and currently protected, Joshua Salomon, a health-policy researcher at Stanford who’s collaborating with Pitzer to model Omicron’s immunological impact, told me. Salomon, Pitzer, and their colleagues estimate that although a significant majority of Americans had rendezvoused with the spike protein by October’s end, fewer than half were still reasonably well guarded against a future infection. (Most retained resilience against severe disease.) People who enter the “well defended” group can also exit it, and join the susceptibles again. Two years, 530 million vaccine doses, and 68 million documented SARS-CoV-2 infections deep into the pandemic, the range of vulnerability in our population has never been larger or more unwieldy. Some high-risk people, never vaccinated or infected, have essentially no protection to speak of; many young, healthy individuals have been triply vaccinated, and are fresh off an Omicron breakthrough. “That’s a huge, huge range,” Wang told me, with a chasm of immunological possibility in between. And none of this accounts for the very real risk that another wonky and wily variant, distinct from Omicron and everything else we’ve seen before, could still upend every rosy immunological assumption we lay down, and send us into yet another devastating surge. And when new variants show up, they will once again reveal the cracks and crevices where protection is lacking. In the same way that single individuals with different exposure histories can’t be expected to achieve the same levels of immune protection, neither can communities with different pandemic histories. Fresh, good-quality immunity simply won’t distribute evenly—we’re likely to see islands, separated by immense seas. Many of these differences will tie straight back to “how inequitably we distributed vaccines,” Elaine Hernandez, a health demographer at Indiana University at Bloomington, told me. Through first, second, and now third doses, we’ve managed to concentrate immune protection among the privileged. Shots remain proportionally sparse in poor communities, rural communities, low-resource communities; unvaccinated people also “tend to concentrate geographically,” Anne Sosin, a health-equity researcher at Dartmouth, told me, seeding fertile ground for the virus to fix in a population and spread. To date, there are still plenty of “pockets that may have not yet had exposure to vaccination or the virus,” Bertha Hidalgo, an epidemiologist at the University of Alabama at Birmingham, told me. [Read: It’s a terrible idea to deny medical care to unvaccinated people] After flitting through urban centers, Omicron will find these isolated enclaves. It will pummel them. It will cause debilitating disease and death, but generate perhaps only a flimsy veneer of protection that, unbuttressed by vaccines, might not successfully ward off future waves. By one estimate, a third to half of all Americans may end up infected by Omicron by mid-February. The variant will not encounter all of those people on equal immunological footing, nor will it create such footing. “Some people will be left with immune houses of straw, others of wood, others of brick,” Sosin said. The virus is not an equalizer; it never has been. Appending vaccinations on top of recent Omicron infections in less protected places could help even the playing field—but there may not be incentive to, as Omicron cases eventually fall away. In many parts of the country where vaccinations have struggled to gain traction, “there is a predominant belief that infection means you are now immune, especially if you were quite sick,” Hidalgo told me. If uptake of shots continues to be sluggish, the gaps in protection that existed before Omicron only stand to widen. This is the texture that national curves and figures obscure: knots of vulnerability that many Americans can easily ignore, but that the virus all too easily exploits. [Read: Our relationship with COVID vaccines is just getting started] Omicron’s cross-country sweep won’t amount to nothing. Immunity will be raised, on average, and “we can still expect it to add friction” to any future path the virus takes, Sarah Cobey, an infectious-disease modeler at the University of Chicago, told me. This may well be the last COVID surge that plays out in such a staggering fashion. We may, for a time, get a touch of reprieve. Even if a new antibody-dodging variant screeches onto the scene, there are “limitations to how this virus can evolve,” Marion Pepper, an immunologist at the University of Washington, told me. By this point, perhaps many immune systems will have seen enough to anticipate what hijinks the virus lobs at us next. But future surges of infection will still carry their own problems. They may be more complicated to track, because they are more local; more asynchronous, because outbreaks will start and end at different times; more patchwork, because of the “communities I worry we’ve left behind,” Sosin told me. As immunity ebbs and flows, our fates will continue to splinter, at the level of both individual and population alike. And yet, our geographies are not so divided that the pathogen won’t pass between them. When the threat is this infectious, it’s not our immunological differences that define us, but the common ground we offer the virus when we allow it to spread. from https://ift.tt/3tNgMb1 Check out http://natthash.tumblr.com “It started as a joke, actually,” Elena Korngold told me. But late last month, the 40-something radiologist from Portland and her family decided that their unsanctioned scheme couldn’t hurt. Elena began the proceedings by unwrapping the sterile swab from a BinaxNOW rapid test for SARS-CoV-2, part of the family’s dwindling supply. She swirled the swab around the insides of each of her nostrils. Then she passed it to her husband, a cardiologist named Ethan, who swirled it around the insides of each of his nostrils. Then their two children did the same. It was “like some sort of religious ritual,” Elena said. The snot-saturated swab went into the test card. The test card showed a negative result. The Korngolds, now bonded by something even thicker than blood, went to their dinner party. Nobody got COVID. Ethan came up with this system on his own, but other people have had similar ideas. Since the Omicron variant began its high-speed march across the United States, at-home tests have become nearly impossible to find in many towns and cities. So some Americans—half-proud, half-embarrassed, and fully desperate to find out whether they’re infected—have tossed the rapid-test instruction manual. To stretch their resources, they’ve started combining samples in their home. When a group test is negative, they conclude that everyone is in the clear, and several testing kits can be saved for future use; if that test is positive, further diagnostics will ensue. But experts say that using rapid tests like this, off-label, won’t produce reliable results. Also, sticking the same swab up multiple noses is, to put it scientifically, gross. [Read: Stop wasting COVID tests, people] The family rapid testers draw their inspiration from pooled testing, a well-established and efficient method used by schools, sports leagues, and hospitals to screen for the virus. In standard pooled testing, people without symptoms might be divided into, say, groups of 10. Mucus from each person is collected (using a fresh swab; I guess I have to specify that now). A lab mixes together a bit of each sample from the group of 10, and then tests the witches’ brew using the PCR method. If a pool is positive, each individual specimen can be retested to figure out who’s carrying the virus. Pooled PCR testing works because the process was designed with that in mind, Jennifer Nuzzo, a senior scholar at the Johns Hopkins Center for Health Security, told me. The samples are each mixed with just the right amount of chemicals to combine into one working test. Squeezing swabs from multiple people into a kit designed to test just one “isn’t really pooled testing,” she said. The rapid tests currently available to Americans don’t come with all the swabs, chemicals, and test tubes that would be necessary to accommodate multiple samples, and jerry-rigging that equipment could lead to contamination or unwanted chemical reactions. Susan Butler-Wu, a clinical microbiologist at the University of Southern California’s Keck School of Medicine, told me that the inclusion of too many human cells from the insides of too many human noses could also produce false negatives on antigen tests by diluting the virus sample. The latter problem doesn’t apply to PCR tests, for which samples are washed of irrelevant genetic material. Then there’s the ick factor. “From a public-health perspective, the idea of sticking swabs up each other’s noses doesn’t sound like a great thing to do,” Nuzzo said. If one person in a household gets COVID, the others aren’t doomed to infection just from living in the same space. In fact, the “secondary attack rate” within a home—which describes the chance of transmitting a virus from one household member to another—appears to be just 15 to 35 percent for SARS-CoV-2. But intranasal promiscuity is a surefire way to increase those numbers, Nuzzo warns, and spread untold other germs besides. Imagine that no one in a family of five has any COVID symptoms, and they have only one test. Imagine also that the family is on their way to visit Grandma. Would a pooled test make a little bit of sense in that scenario? Just a teeny, tiny little bit? Nuzzo doesn’t think so, because scientists have no way of guaranteeing that the test would pick up on a positive case within that family. All five people might conclude that they won’t give Grandma COVID, but that’s not actually what the test was designed to show them. Instead, Nuzzo said, the one test should be used by the person in the house who’s most likely to have been exposed, such as a child attending school or a parent who works in health care or the service industry. The problem isn’t that pooled rapid tests definitely don’t work; it’s that they don’t definitely work. The tests available to Americans are in “a total data-free zone” in this regard, Nuzzo said. Some studies of pooled rapid testing have been carried out on kits that aren’t yet FDA-authorized, though—and their results are promising. A group from E25Bio published a study this summer showing that its rapid test can pick up on one positive, symptomatic sample among a group of 19 negatives. Another group, in Germany, used materials from two existing rapid tests to build a prototype of a pooled rapid test that could detect positive samples among as many as six swabs. Both studies did suggest that pooling rapid tests made them somewhat less sensitive, however. Bobby Brooke Herrera, the chief science officer at E25Bio, who led the company’s study, told me that his team’s results are not an invitation for consumers to “go rogue,” because the current FDA-authorized kits simply aren’t set up for pooled testing. The Korngolds had to share a single swab for their BinaxNOW pooled test and then insert it into the testing card. If they’d had a tube-based test instead—like the QuickVue test from Quidel—they could have stuck four separate swabs into a single vial of buffer solution. But even then, each swab would have absorbed some liquid when it was swished around, Herrera said. “By the time you put the fourth swab in the buffer, you’re probably going to have no buffer left.” Still, with the right tweaks, some of these tests might become poolable. “I’ve been really frustrated that none of the test makers have given instructions for, or provided extra swabs for, or given any indication that it would be okay to pool,” Michal Tal, an immunologist at Stanford, told me. Because of its lower sensitivity, a pooled test might not catch an infection as early as an individual test would, she said, but if pooling allows a family to test more often, they could still come out on top. Tal has made use of pooled rapid testing herself. Unlike the Korngolds, she and her co-testers applied their own swabs, which Tal bought online after making sure they matched the ones included with the test. She was just as horrified at the prospect of sharing mucus as all the other experts I spoke with, calling it both “unsafe” and “gross.” The Korngolds considered—and then put aside—the possibility that their testing experiment could speed infection from one person to another. “It seemed like it would be a reasonable thing to try,” Ethan told me. After all, each of them was up to date on their vaccines, and if the pooled test did come back positive, they had enough tests in the house to identify the culprit. They didn’t even have any trouble working out their order of snot transmission. (Ethan: “We’re close enough as a family that there really couldn’t be any other way.” Elena: “Every family probably has an order in their own mind.”) In the grand scheme of pandemic-induced norm-breaking, the Korngolds said, the shared nose swabbing hardly registered against changes like remote schooling and reusing masks in the hospital. And in the grand scheme of being a family, well, they’ve seen worse. “I would say it is not one of the grossest parts of parenting by a long stretch,” Elena said. The Korngolds insisted that they know perfectly well that their DIY pool setup might not be as accurate as testing one person with one kit, but they don’t regret giving it a go. “I think we’re just like other families that are trying to figure out a way through this,” Ethan told me. And if they get desperate, he and Elena said, they’d happily share snot again. from https://ift.tt/3Ku9sr2 Check out http://natthash.tumblr.com Last Thursday, a group of 20 mothers in Boston met up outside a local high school. Their goal wasn’t to socialize, drink wine, or even share COVID-related tips. They were there for one reason and one reason only: to stand in a circle—socially distanced, of course—and scream. “I knew that we all needed to come together and support each other in our rage, resistance and disappointment,” Sarah Harmon, the group’s organizer, wrote on Instagram before the gathering. Ironically, some 20 other moms who had RSVP’d “yes” had to cancel at the last minute because they or other family members had COVID, Harmon told me. When mothers feel there is no more appealing way to spend an evening than to yell into the frigid January darkness, something is very, very wrong. Parents in the United States are living through a universally terrible moment. For two years, we’ve been spending each and every day navigating an ever-changing virus that’s threatening not only our well-being but our livelihoods. The situation has reached a fever pitch during this wave, when we’re expected to function normally even though nothing is normal and none of the puzzle pieces in front of us fit together. How do we send our kids back to school when no one can find COVID tests and so many students and teachers are out sick? How do we keep our kids home from school when we’re expected to be back at work? How can we be good parents when we are also required to be employees, teachers, nurses, playmates, chefs, therapists, and spouses? As I write this sentence, Netflix is babysitting my daughter, who is home sick with a fever and runny nose that might be COVID—should I feel guilty that I’m not attending to her every need, or is guilt now a luxury parents cannot afford? Parents were defeated long before Omicron. Now we’ve reached a stage of the pandemic where finding the right words to describe our lot is simply an exercise in absurdity. We are broken. We have nothing left in us but screams of anger and pain. Some parents have weathered things worse than others. We have different access to support, different senses of what’s best for our kids, different convictions about masks and distancing and vaccines. But the burden has fallen on us all. Even if we’re somehow physically muddling our way through the pandemonium, our mental health is taking a serious hit. In nationwide survey data being collected now, the Indiana University sociologist Jessica Calarco has found so far that 70 percent of moms, and 54 percent of dads, are feeling overwhelmed and stressed; that about half of parents are feeling depressed and hopeless; and that fewer than 15 percent of mothers, and 25 percent of fathers, are getting enough sleep. “There are really high rates of mental-health struggles across the board,” Calarco told me. For me, what’s especially hard is that I thought it was all getting better—that the worst was over. Yes, there would be more variants, but our vaccines would protect us. My family could finally exhale. But you know that scene in every horror movie when the main character shoots the bad guy, cries in relief that it’s all over, and walks away? And you yell, “No, damn it, you have to check that he’s dead!” Well, we were that tragic hero, and the coronavirus got right back up again. It got right back up, and then it stabbed us in the heart. Case in point: My kids became fully vaccinated in late December, the same week that Omicron began spreading rapidly throughout the U.S. They were so excited to weave some normalcy back into their lives—to go to restaurants, to have sleepovers with friends, to do all the things my husband and I had previously told them were not worth the risk of infection. In fact, we had promised them we would do these things as soon as they were vaccinated. Then, because of Omicron, and the fear that we might inadvertently sicken the grandparents we were supposed to visit over the holidays, we had to go back on our word. They were heartbroken. It’s hard to know what “good parenting” is when you have to make decisions like this—when you find yourself grieving the choices you make to keep your family and community safe. In the living room, my daughter just shivered and asked for a blanket. Don’t get me wrong; some things are much better than they used to be. For my family, the vaccines are a huge relief—but it is also disorienting and disheartening to have reached this milestone only to discover that life is still very much the same. We’re still wearing masks. Vaccinated people are still getting sick. Kids are still being hospitalized, now in record numbers, even if thankfully most children who catch Omicron do fine, vaccinated or unvaccinated. Millions of children still aren’t eligible for a vaccine, and we don’t know yet when they will be, or exactly how much of a difference those vaccines will make. It feels like we don’t have anything momentous to look forward to. There is no much-anticipated cure just over the horizon anymore. There is merely more of the same. More fretting about school closures. More waiting for a new variant to mess everything up once again. Except life’s not really the same, is it? It’s worse. It’s gotten even harder this wave. The early days of the pandemic were devastating, but at least, back then, “there was a consistent story—‘These are the dangers of COVID-19. This is what we have to do,’” Joel Cooper, a psychologist at Princeton who has studied pandemic cognitive dissonance, told me. Now, he said, the messages we are getting seem to contradict one another. We’re expected to go to work, but warned not to get COVID because hospitals are nearly at capacity. We’re told it’s safe to send our kids to school, even as we watch school COVID numbers rise each day. We’re told to get vaccinated, but that vaccines won’t prevent us from getting infected. We’re told to wear masks, but that Omicron is so contagious, they might not protect us. “There’s no consistency anymore,” Cooper said when we spoke last week—a conversation that was interrupted by a text from a close friend telling me that her high-risk daughter had just tested positive for COVID. What we have instead is chaos. As another of my friends, the social worker Carla Naumburg, put it, “Parents are being forced to choose between bad and worse, and we have no idea which option is bad and which is worse.” Many parents have no choices—and no support—at all. Child care for parents of little kids is next to impossible to find. In December 2021, there were 111,400 fewer Americans working in child-care jobs than there were in January 2020, according to the Bureau of Labor Statistics. Meanwhile, the paid-family-leave mandate created by the Families First Coronavirus Response Act expired back at the end of 2020, and there have been no moves to reinstate them. And although the American Rescue Plan Act, signed into law by President Joe Biden in March, promises $39 billion in funding to support the flailing child-care sector, many states haven’t started using the money yet. Parents who are fortunate enough to have day care are hardly able to use it, because their children are being repeatedly exposed to COVID-19. Kjersten Tucker’s 22-month-old son, Zeke, who is enrolled in full-time day care in Lincoln, Nebraska, has received only eight days of care since December 4 because, although he’s remained healthy, he has been quarantined over and over and over again, like in a deranged version of the movie Groundhog Day. “We’ve slogged through this with a combination of help from my mom, my sister, and taking time off—some of it unpaid, as I ran out of paid time off by the end of the year,” Tucker told me. “I don’t know how people are supposed to make this work.” We can’t make this work. That’s the thing. That’s why moms are choosing to spend their nights—their precious moments of child-free time before the next endless day begins—screaming into the darkness. We can’t do this. It isn’t fair. It isn’t sustainable. Then we do it anyway. We hope that when this wave ends, we’ll have a brief respite to compose ourselves before the next one comes, and dream—in the few hours we actually sleep—of finally washing up on the shore of that more normal world we’ve been waiting for all this time. We do it because we have no other choice. from https://ift.tt/3AfXVXD Check out http://natthash.tumblr.com More Americans are now hospitalized with COVID-19 than ever before. Their sheer numbers are overwhelming health-care workers, whose ranks have been diminished by resignations and breakthrough infections. In many parts of the country, patients with all kinds of medical emergencies now face long waits and worse care. After writing about this crisis earlier this month, I heard from a number of readers who said that the solution was obvious: Deny medical care to unvaccinated adults. Such arguments were aired last year, as the Delta variant crested, and they’re emerging again as Omicron spreads. Their rationale often goes something like this:
To be clear, this debate is theoretical: Health-care workers are not denying care to unvaccinated patients, even though, ironically, many told me they’ve been accused of doing so by not prescribing ivermectin or hydroxychloroquine, which are ineffective against COVID but are often wrongly billed as lifesavers. Still, I ran this argument past several ethicists, clinicians, and public-health practitioners. Many of them sympathized with the exasperation and fear behind the sentiment. But all of them said that it was an awful idea—unethical, impractical, and founded on a shallow understanding of why some people remain unvaccinated. [Read: Hospitals are in serious trouble] “It’s an understandable response out of frustration and anger, and it is completely contrary to the tenets of medical ethics, which have stood pretty firm since the Second World War,” Matt Wynia, a doctor and ethicist at the University of Colorado, told me. “We don’t use the medical-care system as a way of meting out justice. We don’t use it to punish people for their social choices.” The matter “is pretty cut-and-dry,” Sara Murray, a hospitalist at UC San Francisco, added. “We have an ethical obligation to provide care for people regardless of the choices they made, and that stands true for our unvaccinated patients.” Unlike vaccine mandates, which limit the jobs unvaccinated people can hold or the spaces they can enter, withholding medical care would be a matter of life or death. And in such matters, medical care should be offered according to the urgency of a patient’s need, not the circumstances leading up to that need. People whose actions endangered themselves, like smokers with lung cancer or cyclists who fall without helmets, still get treated. Those whose actions endangered others, like drunk drivers or terrorists, also get treated. “We are all sinners,” Carla Keirns, a professor of medical ethics and palliative medicine at the University of Kansas Medical Center, told me. “No one has made all the perfect decisions, and any of us could find ourselves in a situation where we are sick.” It is a fundamental principle of modern medicine that “everyone has an equal claim to relief from suffering, no matter what they’ve done or haven’t done,” Daniel Goldberg, a medical historian and public-health ethicist at the University of Colorado, told me. As historical examples show, the most privileged people usually benefit when care is allocated. In the 1960s, when dialysis machines were still rare, a group of seven laypeople were tasked with deciding which patients should receive the lifesaving treatment. Among factors such as age, sex, marital status, wealth, and education, the so-called God Committee also considered which people had “the highest potential of service to society” and were “active in church work.” Unsurprisingly, as later analyses showed, the committee favored middle-aged, middle-class white men. “When it became public, Americans were outraged,” Keirns told me. “They recognized that when you try to make moral distinctions, you end up holding against people circumstances beyond their control.” [Read: What the chaos in hospitals is doing to doctors] A person’s choices are always constrained by their circumstances. Even now, unvaccinated people are not all refusers. Using recent survey data from the U.S. Census Bureau, the health-policy researcher Julia Raifman and the economist Aaron Sojourner have shown that unvaccinated Americans are disproportionately poor—and within the lowest income brackets, people who want or would consider a vaccine outnumber those who would never get one. That they still haven’t gotten the shots might seem inexplicable to people who can just pop into their local CVS. But people who live in poor neighborhoods might not have a local pharmacy, or public transport that would take them to one, or internet access that would allow them to book an appointment. People who earn hourly wages might not have time for a vaccination appointment, or paid sick leave for weathering any side effects. Compared to vaccinated people, unvaccinated people are more likely to live in red states—a correlation that’s commonly seen as a reflection of political choice. But they are also more likely to have other pressing concerns, such as child-care demands, food insecurity, and eviction risk. “Even in Vermont, the most vaccinated state, differences in vaccination closely mirror other social disparities, like household income,” Anne Sosin, a health-equity researcher at Dartmouth, told me. Unvaccinated people are twice as likely to lack health insurance as their vaccinated counterparts, so to a degree, the U.S. is already denying them care. To lean into that denial “would compound the unjust disparities that they already face,” Keirns said. [Read: America is getting unvaccinated people all wrong] Die-hard anti-vaxxers obviously exist, and they tend to be loud and antagonistic. Many health-care workers have told me that they’ve been harangued, threatened, or assaulted by such patients, frequently enough to erode their compassion. Others have said that such patients make themselves harder to treat by resisting medical care and demanding ineffective drugs. But even the most trenchant anti-vaccine attitudes can reflect deeper social problems. Vaccine skeptics might broadly distrust a health-care system that they struggle to access. They might not have regular physicians whom they trust for medical guidance. They might be immersed in right-wing sources who have sown misinformation about vaccines, or communities for whom hesitancy is the norm. “We’ve irrigated many of our rural communities with more misinformation than investments in health care, education, and economic well-being,” Sosin told me. Moral arguments aside, withholding care from unvaccinated people is also logistically unfeasible. No one I talked with could imagine a patient arriving in need and having to wait while a health-care worker checks their vaccine card. But if the hospital crisis gets worse, the urge to conserve resources may force health-care workers to make tough choices. Vaccinated patients are more likely to survive a coronavirus infection than unvaccinated ones, and health-care workers might give them more attention as a medical judgment rather than a moral one. (But such calculus is tricky: “You should preferentially give monoclonal antibodies to unvaccinated people,” Wynia told me, because each dose will be more likely to keep someone out of the hospital.) As health-care workers become more exhausted, demoralized, and furious, they might also unconsciously put less effort into treating unvaccinated patients. After all, implicit biases mean that many groups of people already receive poorer care despite the ethical principles that medicine is meant to uphold. Complex illnesses that disproportionately affect women, such as myalgic encephalomyelitis, dysautonomia, and now long COVID, are often dismissed because of stereotypes of women as hysterical and overly emotional. Black people are undertreated for pain because of persistent racist beliefs that they are less sensitive to it or have thicker skin. Disabled people often receive worse care because of ingrained beliefs that their lives are less meaningful. These biases exist—but they should be resisted. “Stigma and discrimination as a prism for allocating health-care services is already embedded in our society,” Goldman told me. “The last thing we should do is to celebrate it.” During times of crisis, loosening one’s ethical standards is especially tempting, but it’s especially important to hold them high, Wynia told me. That’s a frustrating line for health-care workers to hold, however. They will continue to suffer from burnout, moral distress, and harassment—and many will quit. Medical care will be spread even more thinly. Some people who did everything they could to avoid COVID may die from unrelated conditions. None of this is fair. Nor is it solely the responsibility of unvaccinated people. Many hospitals are also full of other patients who deferred their care for a year or more, and now can’t delay any more. Several institutions mistreated their staff throughout the pandemic, cutting salaries, reducing benefits, and denying time off until many employees decided to quit. Breakthrough infections have forced a record number of the remaining health-care workers away from bedsides. “Even if you said we’re going to downgrade the care we give to [unvaccinated COVID patients], it wouldn’t necessarily upgrade the care for everyone else,” Wynia said. Most important, unvaccinated people are not the only ones transmitting the coronavirus. They’re more likely to do so than vaccinated people, but the latter are still contributing to the virus’s spread—and perhaps substantially so, given Omicron’s ability to partially evade immune defenses. Vaccinated people might have low personal risk of severe illness, but they can still slingshot the virus to vulnerable people who then end up in hospitals. They might not be occupying emergency rooms with their bodies, but they can still help fill those rooms through their actions. As President Joe Biden has continued to talk about a “pandemic of the unvaccinated,” COVID remains a collective crisis--and one driven more by political inaction than personal irresponsibility. It’s the result of an earlier administration that downplayed the pandemic; the current one that went all in on vaccines at the expense of the layered interventions necessary to control the virus; justices and lawmakers who have made it harder, if not impossible, to enact policies that protect people from infection; news sources that seeded misinformation; and social-media platforms that allowed it to proliferate. Blaming or neglecting unvaccinated people won’t save the health-care system or end the pandemic. It will just be the latest manifestation of America’s instinct to punish individuals for societal failures. from https://ift.tt/3tJXOC7 Check out http://natthash.tumblr.com The first COVID-19 vaccine could arrive before Election Day, Donald Trump avowed in the summer of 2020. But government regulators wanted things to work out differently: “The deep state, or whoever, over at the FDA is making it very difficult for drug companies to get people in order to test the vaccines and therapeutics,” he wrote on Twitter. “Obviously, they are hoping to delay the answer until after November 3rd.” Regulators did, in fact, end up slowing the process: In the first week of September, the FDA told vaccine makers to extend their clinical trials by several weeks beyond what they’d planned, in order to gather more safety data. That effectively postponed Pfizer’s request for an emergency use authorization of the mRNA vaccine it had developed with BioNTech until after the election. The agency had been under attack from both sides: The president had wanted regulators to move more quickly, while an alarmed public-health community was pushing for the opposite. In the end, the decision to slow things down was meant to bolster the country’s waning confidence in the forthcoming COVID-19 vaccines and restore the FDA’s reputation for integrity and caution. But the move looks very different in hindsight, with full knowledge of the safety and efficacy of the vaccines and of the body count that amassed shortly after. The economist Garett Jones recently opined that Trump’s scuttled hopes to release a COVID-19 vaccine a few weeks earlier “likely would have saved at least 100,000 American lives.” Could Jones be correct about the human scale of this decision? His colleague at George Mason University, the libertarian economist and blogger Alex Tabarrok, often writes about the “invisible graveyard”: the final resting place for all those killed by the FDA’s bureaucratic foot-dragging. Indeed, one of the more painful lessons we’ve learned about governance during this pandemic is that waiting for more data can be a leading cause of death. But just how deadly was the government’s choice to slow down Pfizer’s and Moderna’s research in the fall of 2020? Let’s recall the context for the FDA’s decision. During the first year of the pandemic, it was easy to freak out a little bit as the president pushed wishful but unproven COVID-19 therapies along the FDA’s high-speed pathway for emergency use authorization (EUA). In particular, hydroxychloroquine and convalescent plasma were touted as miracle cures and widely distributed to patients even in the absence of convincing data showing that they worked. As the election approached that fall, and Trump intensified his attacks on the agency, those two messy episodes set the stage for a bigger regulatory standoff. The stakes had seemed much lower for the “miracle cures” because those were typically being given to people already sick with COVID. The new mRNA injections, if authorized, would be delivered to millions of healthy, uninfected Americans, most of whom were unlikely ever to develop severe disease. “We don’t do EUAs for vaccines,” the pediatrician and vaccinologist Peter Hotez told Yahoo News on September 1. “It’s a lesser review, it’s a lower-quality review, and when you’re talking about vaccinating a large chunk of the American population, that’s not acceptable.” The FDA had already signaled that it would make the EUA process more demanding for the COVID-19 vaccines than it had been for medical products in the past: The vaccine makers would need to show results from a large-scale Phase 3 clinical trial. Pfizer initially expected to have these by the end of October, when its 44,000-person clinical trial would have accrued enough data points for researchers to perform a first statistical analysis. Then the FDA applied the brakes, telling Pfizer and Moderna that it wanted additional safety data. More specifically, it wanted the companies to have tracked the health of at least half of their clinical-trial subjects for 60 days following the second dose. The thinking was that most adverse reactions occur within the first 42 days of vaccination, but out of an abundance of caution, the FDA would extend that period to 60 days, which was still much shorter than the six months of follow-up expected for a full vaccine approval. [Read: The FDA really did have to take this long] FDA scientists touted this new proposal as “EUA Plus.” Marion Gruber, a former head of the agency’s vaccine office, told me it was not a direct response to the president’s actions. “We tried to separate ourselves from whatever politics was going on,” she said when I interviewed her last year. Nevertheless, she was concerned that the public’s confidence in the vaccines was on the decline that fall. Gallup poll numbers indicate that Americans’ willingness to take an approved COVID-19 vaccine had dipped from 66 percent that summer to just 50 percent in September. Fearful that the FDA bureaucrats could be overruled by the White House, outside scientists locked arms and sent a letter to Pfizer’s CEO, Albert Bourla, on September 25, telling him that the proposed safety delay would be crucial for securing “the utmost trust in the vaccine and the science behind it.” They warned that a “premature application would prolong the pandemic” and “severely damage” Pfizer’s reputation. In the end, Pfizer did not reveal its trial’s favorable results until November 9—six days after the election. The company had originally planned to consider submitting an EUA request to the FDA with just 32 data points; instead it gathered 94, and it waited another 11 days to accrue the requested safety data, plus even more data showing how well the vaccine worked, before making its filing. With no serious safety issues and vaccine efficacy coming out in the mid-90s, outsiders were more than satisfied. So was the FDA, which finally granted Pfizer’s vaccine an EUA on December 11. The claim that the delay killed 100,000 people assumes that the process got backed up by six to eight weeks, and that the vaccine could have been rolling out by the end of October. Having reported a book on the COVID-19 vaccine race, I find this imagined timeline unrealistic. The FDA was evaluating a new vaccine for use against a new disease, based on a technology—mRNA—that had never before been authorized. Even given the clear sense of urgency, it’s hard to imagine that the review process could have been shortened by more than a week, as happened in the United Kingdom. And even if authorization had been instantaneous, we still don’t know how many doses Pfizer would have had available for distribution by the end of October. Bourla told The Washington Post on September 29 that he expected to have “hundreds of thousands [of doses] ready” in October and “a few million in November”—but production did not ramp up as quickly as expected. In light of all these facts, the regulatory move probably slowed the rollout by about two to three weeks at most. Without the additional safety requirement, Pfizer could theoretically have stuck with its initial plan and filed for an EUA before the presidential election. Following FDA review, a rollout might have begun in the third week of November. A quicker process might have kept public confidence in the vaccine depressed for a little while longer, but more than enough people would have still been willing to roll up their sleeve for a jab; after all, it took about four months for vaccine supply to catch up with demand. And with so few doses available for this earlier rollout, they would have had to have been primarily targeted to the most vulnerable: the 1.4 million elderly people in nursing homes, where about 5,000 residents were dying from COVID each week in early December 2020. The vaccines would have cut mortality with the first dose, leading to a steep drop in cases in December, rather than the January decline we saw. At my request, Claus Kadelka, a mathematician at Iowa State University who has studied COVID-19-vaccination strategies, modeled what would have happened if 2 million bonus doses had been available for nursing homes starting on November 23. Depending on the details of the scenario, he estimated that those extra doses could have saved 6,000 to 10,000 lives. That doesn’t necessarily mean that the FDA botched its risk-benefit calculus based on what was known at the time, or that the public-health community was out of line in calling for a cautious process. In August and September, when many concerns were raised, COVID case numbers were at a lull, and no one was certain how quickly they would take off again. And though no major safety events were caught during those extra few weeks of data collection, who’s to say that things couldn’t have worked out otherwise? To argue that the wait was worthless is akin to saying I shouldn’t wear my seat belt tomorrow because I didn’t get in a car accident today. What if a more serious issue had emerged two months after the second dose? It would have harmed not only the uptake of the COVID vaccine (and maybe vaccines for other diseases already on the market), but also the teetering reputation of the FDA. That, too, could have had fatal consequences. “The truth is that trust in vaccines is critical,” said Peter Marks, the acting head of the agency’s vaccines office, when I reached out to him last week to ask about the claim that the safety delay had cost thousands of lives. “If we didn’t have the data from those extra weeks … we would not have been anywhere near as sure that the vaccines worked—and vaccine hesitancy, which was pretty bad to begin with, would have been even worse.” The scrutiny of the agency’s shifting goalposts also ignores an important and disturbing fact: An alternative path had been available to the FDA and the vaccine makers all along, one that could have avoided the EUA dilemma while still granting early access to the most vulnerable members of the population. In October 2020, Deborah Birx, the coordinator of the White House Coronavirus Task Force, was on the ground in North Dakota and alarmed by how quickly COVID was spreading through nursing homes. As I reported in my book, The First Shots, she began to think that the vaccines should be distributed to residents under what’s known as an expanded access, or compassionate use, protocol. This FDA program is typically used by drug companies to provide patients who have rare diseases or cancers with new drugs that are likely safe but have not yet been proved effective in clinical trials. (Prior to the emergency use authorization of convalescent plasma, the Mayo Clinic provided the therapy to more than 70,000 COVID patients via this protocol.) If a compassionate use program for COVID-19 vaccines had gone forward, doctors would have been able to prescribe them to nursing-home residents, even as the vaccine makers completed their clinical trials with integrity and gathered all the safety data requested under the “EUA Plus” requirements. According to Marks, Birx asked Anthony Fauci and FDA Commissioner Stephen Hahn to encourage Pfizer and Moderna to apply for that program. (Birx declined to comment for this article; Fauci and Hahn did not respond to inquiries.) If the companies had agreed, and if their applications had been granted, how much time could have been gained is hard to say. Such a complex program would have required close monitoring by the CDC and major tweaks to Operation Warp Speed’s vaccine-distribution plans. In any event, conversations around the topic apparently sputtered, and the companies never applied for compassionate use. (Moderna did not reply to a request for comment on this decision. Pfizer responded with a broadly worded statement that read, in part: “We worked closely with the FDA as we developed our vaccine to determine the most appropriate regulatory pathway to make the vaccine available to the public.”) Perhaps Birx’s efforts would have gathered more steam with a different president, or if an election were not about to happen, or if her proposal had been floated earlier. Unlike in time-travel stories, the course of history rarely pivots on a single event. The actual timing of the COVID-19 vaccines’ release resulted from a complicated mix of bureaucratic caution, political calculations, and the choices made by vaccine manufacturers. While the benefits of the vaccines have become very clear since then, the precise human cost of that short delay remains a mystery. When you buy a book using a link on this page, we receive a commission. Thank you for supporting The Atlantic. from https://ift.tt/3AdVjtb Check out http://natthash.tumblr.com |
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