A quick skim of the CDC’s latest COVID guidelines might give the impression that this fall could feel a lot like the ones we had in the Before Times. Millions of Americans will be working in person at offices, and schools and universities will be back in full swing. There will be few or no masking, testing, or vaccination mandates in place. Sniffles or viral exposures won’t be reason enough to keep employees or students at home. And requirements for “six feet” will be mostly relegated to the Tinder profiles of those seeking trysts with the tall. Americans have been given the all clear to dispense with most of the pandemic-centric behaviors that have defined the past two-plus years—part and parcel of the narrative the Biden administration is building around the “triumphant return to normalcy,” says Joshua Salomon, a health-policy researcher at Stanford. Where mitigation measures once moved in near lockstep with case numbers, hospitalizations, and deaths, they’re now on separate tracks; the focus with COVID is, more explicitly than ever before, on avoiding only severe illness and death. The country seems close to declaring the national public-health emergency done—and short of that proclamation, officials are already “effectively acting as though it’s over,” says Lakshmi Ganapathi, a pediatric-infectious-disease specialist at Boston Children’s Hospital. If there’s such a thing as a “soft closing” of the COVID crisis, this latest juncture might be it. The shift in guidelines underscores how settled the country is into the current state of affairs. This new relaxation of COVID rules is one of the most substantial to date—but it wasn’t spurred by a change in conditions on the ground. A slew of Omicron subvariants are still burning across most states; COVID deaths have, for months, remained at a stubborn, too-high plateau. The virus won’t budge. Nor will Americans. So the administration is shifting its stance instead. No longer will people be required to quarantine after encountering the infected, even if they haven’t gotten the recommended number of shots; schools and workplaces will no longer need to screen healthy students and employees, and guidance around physical distancing is now a footnote at best. [Read: New COVID vaccines will be ready this fall. America won’t be.] All of this is happening as the Northern Hemisphere barrels toward fall—a time when students cluster in classrooms, families mingle indoors, and respiratory viruses go hog wild—the monkeypox outbreak balloons, and the health-care system remains strained. The main COVID guardrail left is a request for people to stay up to date on their vaccines, which most in the U.S. are not; most kids under 5 who have opted for the Pfizer vaccine won’t even have had enough time to finish their three-dose primary series by the time the school year starts. In an email, Jasmine Reed, a public-affairs specialist for the CDC, suggested the Pfizer timing mismatch wasn’t a concern, because “a very high proportion of children have some level of protection from previous infection or vaccination”—even though infection alone isn’t as powerfully protective as vaccination. “It’s like they're throwing their hands up in the air,” says Rupali Limaye, a public-health researcher and behavioral scientist at Johns Hopkins University. “People aren’t going to follow the guidance, so let’s just loosen them up.” For many, many months now, U.S. policy on the virus has emphasized the importance of individual responsibility for keeping the virus at bay; these latest updates simply reinforce that posture. But given their timing and scope, this, more than any other pandemic inflection point, feels like “a wholesale abandonment” of a community-centric mindset, says Arrianna Marie Planey, a medical geographer at the University of North Carolina at Chapel Hill—one that firmly codifies the “choose your own adventure” approach. Reed, meanwhile, described the updates as an attempt to “streamline” national recommendations so that people could “better understand their personal risk,” adding that the CDC would “emphasize the minimum actions people need to take to protect communities,” with options to add on. (Ashish Jha, the White House’s top COVID adviser, did not respond to multiple requests for comment.) It is true that, as the CDC epidemiologist Greta Massetti said in a press briefing last week, “the current conditions of this pandemic are very different.” The country has cooked up tests, treatments, and vaccines. By some estimates, roughly three-quarters of the country harbors at least some immunity to recent variants. But those tools and others remain disproportionately available to the socioeconomically privileged. Meanwhile, Planey told me, people who are poor, chronically ill, disabled, immunocompromised, uninsured, racially and ethnically marginalized, or working high-risk jobs are still struggling to access resources, a disparity exacerbated by the ongoing dearth of emergency COVID funds. Know your risk, protect yourself, the infographics read—even though that me before we concept is fundamentally incompatible with tempering an infectious disease. If wide gaps in health remain between the fortunate and the less fortunate, the virus will inevitably exploit them. [Read: Of course Biden has COVID] The most recent pivots are not likely to spark a wave of behavioral change: Many people already weren’t quarantining after exposures, or routinely being tested by their schools or workplaces, or keeping six feet apart. But shifting guidance could still portend trouble long-term. One of the CDC’s main impetuses for change appears to have been nudging its guidance closer to what the public has felt the status quo should be—a seemingly backward position to adopt. Policies are what normalize behaviors, says Daniel Goldberg, a public-health ethicist at the University of Colorado Anschutz Medical Campus. If that process begins to operate in reverse—“if you always just permit what people are doing to set your policies, guaranteed, you’re going to preserve the status quo.” Now, as recommendations repeatedly describe rather than influence behavior, the country is locked into a “circular feedback loop we can’t seem to get out of,” Ganapathi told me. The policies weaken; people lose interest in following them, spurring officials to slacken even more. That trend in and of itself is perhaps another form of surrender to individualism, in following the choices of single citizens rather than leading the way to a reality that’s better for us all. No matter how people are acting at this crossroads, this closing won’t work in the way the administration might hope. We can’t, right now, entirely shut the door on the pandemic—certainly not if the overarching goal is to help Americans “move to a point where COVID-19 no longer severely disrupts our daily lives,” as Massetti noted in a press release. Maybe that would be an option “if we were genuinely at a point in this pandemic where cases didn’t matter,” says Jason Salemi, an epidemiologist at the University of South Florida. Relaxed guidance would be genuinely less “disruptive” if more people, both in this country and others, were up to date on their vaccines, or if SARS-CoV-2 was far less capable of sparking severe disease and long COVID didn’t exist. (Reed, of the CDC, told me that the agency’s “emphasis on preventing severe disease will also help prevent cases of post-COVID conditions,” adding that “vaccines are an important tool in preventing and treating post-COVID conditions”—even though immunization can’t completely block long COVID and seems to relieve its symptoms in only a subset of people.) Guaranteed paid sick leave, universal health care, and equitable resource allocation would also reduce the toll of loosening the nation’s disaster playbook. Layered onto this reality, however, chiller guidelines will only spur further transmission, Planey told me, upending school and workplace schedules, delaying care in medical settings, and seeding more long-term disability. For much of the pandemic, a contingent of people has been working to advance the narrative that “the measures to prevent transmission are the cause of disruption,” Stanford’s Salomon told me; vanishing those mitigations, then, would purport to rid the country of the burdens the past couple years have brought. But unfettered viral spread can wreak widespread havoc as well. [Read: The BA.5 wave is what COVID normal looks like] Right now, the country has been walking down an interminable plateau of coronavirus cases and deaths—the latter stubbornly hovering just under 500, a number that the country has, by virtue of its behaviors or lack thereof, implicitly decided is just fine. “It’s much lower than we’ve been, but it’s not a trivial number,” Salemi told me. Held at this rate, the U.S.’s annual COVID death toll could be about 150,000--three times the mortality burden of the worst influenza season of the past decade. And the country has little guarantee that the current mortality average will even hold. Immunity provides a buffer against severe disease. But that protection may be impermanent, especially as the virus continues to shapeshift, abetted by unchecked international spread. Should the autumn bring with it yet another spike in cases, long COVID, hospitalizations, and deaths, the country will need to be flexible and responsive enough to pivot back to more strictness, which the administration is setting Americans up poorly to do. Acceptance of the present might presage acceptance of a future that’s worse—not just with SARS-CoV-2 but with any other public-health threat. Months on end of weakening guidelines have entrenched “this idea that mitigation can only be dialed in one direction, which is down,” Salomon told me. If and when conditions worsen, the rules may not tighten to accommodate, because the public has not been inured to the idea that they should. “If it’s going to be 600 deaths a day soon,” or perhaps far more, Ganapathi told me, “I won’t be surprised if we find a way to rationalize that too.” from https://ift.tt/Aj3kbsi Check out http://natthash.tumblr.com
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By this point, the pandemic saga has introduced us to a cast of recurring characters. Among them are the Chill Friend, who is totally over COVID precautions at this point, and the Unlucky Acquaintance, who has had COVID three times and brings it up whenever someone else falls sick. And then there is the Person Whose Roommate Has COVID. You know the type: They’ll describe, in the hushed tones usually reserved for tragic gossip, how and when their live-in friend, partner, child, or whoever came down with the virus—before interjecting, “But I feel fine! … For now.” Nervous laughter ensues. Whether their house is dealing with a blazing-fever situation or a mild-cough one, Person Whose Roommate Has COVID always has the same underlying worry: Am I next? The answer can feel like a definitive yes. The perfect conditions to catch the coronavirus might look something like a shared home, where families, friends, or near strangers end up spending lots of time together in confined spaces. Even if they’re not sleeping in the same bedroom, roommates in all their various forms are sitting down at the dinner table together or squeezing past one another on the way to the bathroom—potentially misting the virus into the air in the process. And it doesn’t help that the latest variant, BA.5, is the most contagious yet. If Person Whose Roommate Has COVID has been breathing the same air all this time, is there even a point to quarantining? It can be tempting to throw up your hands, assume that a positive test result is coming, and cozy up on the couch for an extended Netflix marathon. But while the attitude of Person Whose Roommate Has COVID is natural, it’s also misplaced. All members of a household will not inevitably get COVID if someone falls sick—not even close. One recent roundup of 135 studies found that the overall spread of disease within a home—an epidemiological phenomenon that is unfortunately named “household secondary attack rate”—was 42.7 percent for the earliest forms of Omicron. The offshoots we’ve seen since then are more transmissible, so the chance of getting the virus from a roommate is now probably closer to 50 percent, Bob Wachter, the chair of UC San Francisco’s department of medicine, told me. “It’s about a coin flip,” he said. “The key thing is that it’s certainly not a sure thing.” That is especially useful to keep in mind now that the CDC has updated its COVID guidelines, no longer suggesting that Americans who have been exposed to the virus need to quarantine for five days. It was already happening, but now even more People Whose Roommate Has COVID won’t be taking precautions. Still, the new policy doesn’t change what we know about COVID in the home. Separating yourself from the sick person is tedious and sometimes impossible, but if you can, it’s worth the hassle. The explanation for why people aren’t destined to get COVID from their roommates “is a complex brew,” Wachter said. He and other experts I spoke with agreed on its main components: the infectiousness of the sick person (the “index case”), the immunity of the other people in the household, the virus itself, and the nature of the home. Unfortunately, there’s no good way of nailing down just how infectious someone is. Infectiousness varies over time, and a positive test isn’t necessarily a sign that an infection is just beginning—especially these days, when people who are symptomatic can still sometimes get a series of negative rapid-test results. If your roommate comes down with symptoms and gets a positive test result soon after, there is little doubt that person is contagious at that moment. But whether they were infectious prior to the test is not a given. “I wouldn’t assume that just because your loved one was sick for a day or two [before testing] that you were exposed to a contagious person during that time. It’s unknown,” Jennifer Nuzzo, an epidemiologist at Brown University’s School of Public Health, told me. COVID symptoms usually but don’t necessarily equal contagiousness, she explained; confusingly, a vaccinated person may develop symptoms before testing positive on a rapid antigen test because their immune system, primed by the vaccine, is merely reacting to the virus. If you live with that person, “it could give you a glimmer of hope that you could still not get infected, were you to take additional precautions,” Nuzzo said. And like so many other aspects of COVID, an infected person’s ability to spread the virus also greatly depends on their vaccination status. Remember that the coronavirus is not all or nothing; it builds up in the body incrementally until it spills over and out to other people. In other words, contagiousness hinges on viral load, which may vary with the strength of someone’s immune response. Compared with someone who is unvaccinated, an infected person who is up to date on their shots has a better chance at keeping the viral load down, meaning they are poised to shed less virus to other members of the household. The vaccination status of other people in the home is “perhaps even more important” than that of the index case, Jodie Guest, a professor at Emory University’s Rollins School of Public Health, told me. Even with the newest variants, vaccines still provide some protection against infection (and even better protection against severe illness and death). In the big analysis of studies, the variant with the highest household-secondary-attack rate was Omicron, but the next-highest was not the second-most-transmissible variant, Delta. Instead it was Alpha, the first major coronavirus variant, which emerged at the end of 2020—before vaccines were widely available in the United States. “That’s solid evidence that the vaccines definitely are preventing a skyrocketing [household] secondary-attack rate,” Guest said. Of course, the protection imparted by vaccination fluctuates with numerous factors: the timing of vaccines and boosters, previous infection with old or new variants, and genetic susceptibility, among others. All other factors being equal, a home made up entirely of unvaccinated people would be expected to have a higher household-attack rate than a home of all boosted people. Then there is the virus itself. It’s frustratingly good at infecting us humans—a major reason this pandemic has dragged on and on—but it’s still not contagious enough to infect everyone in a household in every single case. “There is some inefficiency in transmission,” Amesh Adalja, an infectious-disease physician at Johns Hopkins University, told me. “It’s clearly not in the same league as measles,” an airborne pathogen that has a household-secondary-attack rate of more than 90 percent. And although Omicron may have qualities that contribute to its high transmissibility—such as a potentially shorter incubation period and larger viral load—those alone might not be enough to fully explain its higher attack rate, Nuzzo said. It’s possible, even likely, that the more important factor is waning immunity, she explained; just about a third of Americans have gotten their first booster shot. The factor that is perhaps the most challenging to deal with is the nature of the household itself. Unlike getting vaccinated or putting on a mask, most people cannot change their living situation the moment a double bar materializes on a rapid test. If you live in a mansion, well, congrats. It is much easier to stay distanced and avoid getting sick in a big house with several bedrooms and a backyard. Less so for poorer people who might live in a cramped apartment with a single shared bathroom. Research suggests that poor immigrant neighborhoods—the Bronx, in New York, and Pico Union, in Los Angeles—were among the hardest hit in the pandemic because homes in these areas are disproportionately overcrowded. In multigenerational homes with young children or elderly people who need care, fully isolating is almost impossible. “These are all things that are incredibly variable and specific to people’s situations,” Guest said, “and are going to be inequitably distributed.” This complex brew has an invisible, maddeningly uncontrollable secret ingredient: luck. Sometimes, a person who is fully vaccinated and boosted falls sick, while a less diligent person dodges infection over and over again. “This is the hardest piece,” Wachter said. “It’s very hard to predict.” Despite our best efforts to protect ourselves and others, COVID can still break through, seemingly at random. So many factors influence susceptibility that accounting for all of them at once is nearly impossible. Taking all the factors into account, that Person Whose Roommate Has COVID faces baseline 50–50 odds of getting sick is nothing to celebrate. Lots of people in this situation end up falling sick themselves. But it is a reminder that nothing about this virus is preordained. A household can tilt its chances in a favorable direction by doing all the usual, proven things: wearing good masks, opening windows to increase ventilation (and buying a HEPA filter if you can afford one), separating from the sick person when possible, and testing often. If you have no choice but to share a bed with someone who is sick, the CDC recommends sleeping head to toe. Vulnerable people, especially those 65 and over, should have a plan for getting Paxlovid, and everyone should stay up to date on vaccinations and boosters, Nuzzo said. “There’s no point in waiting for a different vaccine in the fall if you get it between now and the fall,” she said. These sorts of measures are really worth the trouble: The problem with not trying is that it can lead to more infections at home, “and then you’ve got a whole other mess,” Adalja said. “Why prolong it?” There is no way around this: Managing COVID in a household is cumbersome, and it will be far easier for people who have more resources. Some will be able to follow every expert recommendation to the letter; others will have to be more selective. Parents of a sick child may choose not to separate—not because they don’t care about getting infected, but because the risk of doing so is outweighed by the need to care for their child. “Those are fair, emotional, familial conversations,” Nuzzo said. “Some people want permission to not try to stay aseptically isolated from their loved one, and I completely understand why they may want to do that.” Now that the latest CDC guidance puts COVID safety into the hands of Americans—well, even more than it already was—Person Whose Roommate Has COVID has yet another reason not to quarantine. The hope is that they aren’t infectious. However, there’s always a risk that they may be, and the best way for them to keep protecting others is to remain as cautious as possible at home. The coronavirus is known to spread more easily in households than anywhere else, so doing one’s best to separate from a sick person at home can go a long way in preventing the virus from making the leap from your house to the world outside. Especially heading into the fall and winter, when case numbers are expected to jump even higher, trying to tamp down on household transmission is a small thing we can all do to attempt to keep this virus under control. No matter what, we will continue to meet People Whose Roommate Has COVID, but we can help them avoid becoming People Who Have COVID Too. from https://ift.tt/B7AyreM Check out http://natthash.tumblr.com Once again, the United States is messing up its approach to vaccines. Three months into its monkeypox outbreak, just 620,000 doses of the two-injection Jynneos shot—the nation’s current best immune defense against the virus—have been shipped to states, not nearly enough to immunize the 1.6 million to 1.7 million Americans that the CDC considers at highest risk. The next deliveries from the manufacturer aren’t slated until September at the earliest. For now, we’re stuck with the stocks we’ve got. Which is why the feds have turned to Inoculation Plan B: splitting Jynneos doses into five, and poking them into the skin, rather than into the layer of fat beneath. The FDA issued an emergency-use authorization for the strategy yesterday afternoon. This dose-sparing tactic will allow far more people to sign up for doses before summer’s end; if successful, it could help contain the outbreak in the U.S., which currently accounts for nearly a third of the world’s documented monkeypox cases. But this decision is based on scant data, and the degree of protection offered by in-skin shots is no guarantee. The FDA is now playing a high-stakes game with the health and trust of people most vulnerable to monkeypox—an already marginalized population. Call it a bold decision; call it a risky gamble: It may be the best option the country currently has, but one the U.S. could have avoided had it marshaled a stronger response earlier on. [Read: America should have been able to handle monkeypox] Little is known about how Jynneos performs against monkeypox even in its prescribed dosing regimen, the so-called subcutaneous route; the new method, intradermal injection, is a murkier proposition still. “We are in a very data-thin zone,” says Jeanne Marrazzo, an infectious-disease physician at the University of Alabama at Birmingham. The shot was approved for use against smallpox and monkeypox in 2019. But to date, researchers don’t have a strong sense of how well it guards against disease or infection or how long protection lasts. Although scientists know that two doses of Jynneos can elicit similar numbers of antibodies as older poxvirus vaccines, no estimates of the vaccine’s true efficacy, from large-scale clinical trials, exist; a human study in the Congo hasn’t yet reported results. And though firmer data have shown that the vaccine keeps lab monkeys from getting seriously sick, “I don’t necessarily trust making the clinical decisions” based just on that, says Mark Slifka, a vaccinologist at Oregon Health & Science University. It’s not even clear if Jynneos can stop someone from transmitting the virus, especially now that many cases seem to be arising via skin-to-skin contact during sex, an understudied form of spread. The emergency switch to lower-dose intradermal administration has been tested with other vaccines, among them the shots that guard against yellow fever and influenza. Skin is rife with specialized defensive cells that can snatch up bits of vaccines and ferry them to other immune fighters, “so you can use a smaller dose and get similar responses” to a full-size subcutaneous shot, says Jacinda Abdul-Mutakabbir, a pharmacist at Loma Linda University, in California. One lone study from 2015 suggests that this logic should hold for Jynneos—at least among the trial’s participants, healthy adults who were mostly young and white. In that group, the subcutaneous and intradermal shots were “quite comparable” at rousing antibodies in the body, which is “very encouraging,” says Kathryn Edwards, a vaccinologist at Vanderbilt University who helped conduct the study. But that’s not the same as bona fide protection against the virus. And what happened in that single study won’t necessarily play out in the real world, especially in the context of the current outbreak, which differs from its predecessors in demographic and size. “I do think these data need to be confirmed,” Edwards told me. Most of the cases so far have been in men who have sex with men, many of them living with HIV—a community whose immune systems don’t look the same as the population at large, and in whom vaccines may not take as well, or for as long, Slifka told me. And yet the FDA has charged ahead “completely based on” that 2015 study, says Alexandra Yonts, a pediatric infectious-disease physician at Children’s National Hospital. In a statement, the agency explained that it had “determined that the known and potential benefits of Jynneos outweigh the known and potential risks” for green-lighting the intradermal route. Delivering vaccines into skin leaves little room for error. The tuberculosis skin test is also administered intradermally; Marrazzo has seen “dozens of those messed up.” People have bled or been bruised. Needles have gone too deep—a mistake that can slash effectiveness—or too shallow, letting liquid ooze back out. Intradermal injections are an uncommon and difficult procedure, requiring additional training and specialized needles. “There is going to be some degree of error,” says Kenneth Cruz, a community-health worker in New York. “People are going to wonder if they’re protected, and it’s going to be difficult to check.” Already, health-care providers are having “issues staffing vaccination clinics for subcutaneous injections,” says Boghuma Kabisen Titanji, an infectious-disease physician at Emory University; the switch to intradermal will exacerbate those shortages and could raise further vaccination barriers for people without reliable health-care access. Intradermal shots can also come with more irksome side effects, as the 2015 study suggested, including redness and swelling at the injection site that can be “pretty robust and severe,” Marrazzo told me. People who get their first doses might not come back for more, defeating the point. Dose-splitting is still “a much better way to go,” Yonts told me, than skipping or seriously delaying second doses—which has already happened in cities such as New York; Washington, D.C.; and San Francisco—in an effort to conserve supplies. Even elsewhere, second appointments are very hard to get. “I do not know anyone who’s gotten the second dose,” says Nick Diamond, one of the investigators behind RESPND-MI, an LGBTQ-led survey of monkeypox symptoms and networks. Which isn’t great: After just one shot, antibody levels “barely budge,” Yonts said, leaving people vulnerable until two weeks after the second injection is complete. (Another vaccine, ACAM2000, is available but can cause serious side effects, and isn’t recommended for people who are immunocompromised, including those with HIV.) With no other good choices on the table, dose-splitting is the only road to take. “I don’t really see another viable option,” Marrazzo told me. That doesn’t erase the fact that the nation squandered its chance with Inoculation Plan A: leveraging its considerable resources to deploy the tests, treatments, and vaccines to contain the outbreak early on, and keep subcutaneous shots in contention. Now, with about 9,500 recorded infections among Americans nationwide—a definite undercount—the door to that has slammed shut. Sticking with the strategy of two full subcutaneous doses for all was projected to leave us with “no vaccine by October,” Marrazzo said. Plan B, though, could have real costs, depressing vaccine demand and trust. Already, “we haven’t been able to answer questions about the level of protection,” Diamond told me, “which makes it really hard for people to make decisions around risk.” The best Abdul-Mutakabbir has been able to tell her patients is that “receiving this vaccine will likely protect you more than if you had not,” she said. Which doesn’t do much to “allay fears and worries,” Cruz told me, especially after more than a year of confusing and conflicting messages about COVID vaccination. [Read: What should worry most Americans about our monkeypox response] Joseph Osmundson, a microbiologist at NYU and a RESPND-MI investigator, told me that he thinks the Biden administration did not properly consult members of vulnerable communities before plowing ahead with dose-splitting. And he worries that disparities could arise if subcutaneous shots end up outperforming intradermal ones: People who had the socioeconomic privilege to find and access appointments early will have gotten the primo doses, while those already at higher risk skate by on a smaller serving of immunity, exacerbating the inequities the outbreak has already begun to exploit. The numbers alone could leave a bad taste: “If I were standing in line to get a fifth of a vaccine,” Diamond told me, “I would wonder why my health is valued less.” Dose-splitting is a stopgap—“not a solution” that’s sustainable, says Luciana Borio, a former acting chief scientist at the FDA. The monkeypox outbreak could stretch on for many months, or become endemic in animals. Eventually, boosts may be necessary; ACAM2000 may yet have a larger role to play. The U.S. will need clinical trials to understand which dosing strategies actually work best, and in whom—and the populations most affected, especially men who have sex with men, should be involved in those decisions along the way. Officials must be “transparent about the gaps that exist,” Abdul-Mutakabbir told me, “and be intentional about working to fill those gaps.” Still, as news of the dose-splitting decision continues to percolate out into the population, an inadvertent message may already be getting sent: “The government is placing the onus on community members to protect themselves,” Cruz said. “But we’re in this position because the government failed.” Should the administration’s big bet on dose-splitting not pay off, Osmundson said, for those who have so far borne the outbreak’s brunt, “that will be the nail in the coffin of any public trust.” from https://ift.tt/9KzNjpo Check out http://natthash.tumblr.com Ah, summertime! Right about now, you might be yearning or even packing for your dream vacation—one full of rest and relaxation. Long, languorous days of doing nothing, perhaps lying on the beach or holed up in a cabin somewhere far from the city. Imagine how happy you’ll be. Then imagine how bored you’ll be. Lying in the blazing sun on the beach, you’ll be stuck in your head with plenty of time to think about your problems. To your surprise, you might start feeling lonely and bored—even restless—with all this free time. The truth is, when it comes to vacation, rest and relaxation aren’t just overrated. They might even work against the very things a trip is meant to cultivate: a mental reset, a sense of relaxation, happiness. A better vacation is one in which vigorous exercise features prominently. That way, you can take a break not just from work and routine life but also from the tyranny of self-absorption. Recently, a close friend and his wife invited my husband and me to join them on a cycling vacation. I was a bit nervous; I’m a serious swimmer but not an experienced cyclist. Riding 30 to 40 miles a day through Vancouver’s impressive hills for five days sounded like hard work, not pleasure. But by the end of our first day of riding, I was overtaken by euphoric calm. [Read: Plan ahead. Don’t post. And seven other rules for a happy vacation.] The work of managing hills by bike has a special way of commanding your attention. I was so busy thinking about whether I could hold my pace for the next rise and how fast I could go downhill without wiping out that I had no time to think about myself. I started looking forward to getting up early and hitting the road. I took in the mountains and forests, dense with cedar and fir, but my focus was really on the bike and the road. The wandering mind, which is often self-absorbed, is generally not a happy one. In one study, researchers randomly pinged people on their smart devices during the day to ask them what they were doing and how they felt. The team found that the participants were happiest when they were involved in an activity and not thinking much about anything else, and least happy when they were daydreaming and preoccupied with their own thoughts. Such mind-wandering was at least somewhat frequent in all activities reported except sex. In another study, subjects who remained physically busy were happier than those who were inactive, even when they were forced into being busy. When we are really engaged in activities, we have less opportunity to worry and feel bad. That might be because focusing on a task temporarily quiets the default network, a set of interconnected brain regions that is most active when a person is self-focused, thinking about the past or imagining the future. The default network is deactivated when people focus on the outside world—and, intriguingly, when they use psychedelics. In other words, when our full attention is taken up by something outside of ourselves, we are freed from the uncomfortable burden of self-awareness. [Read: The reason our minds wander] Scientists can’t brain-image people in motion, but it’s a good bet that exercise quiets the default network. To some extent, other absorbing activities, such as doing math puzzles or knitting, might suffice too. Ditto cooking and painting. But I think none has the unique effect of physical exertion, which not only suspends self-absorption but triggers biological effects—such as the release of endorphins—that bring about a sense of well-being and, if we’re lucky, rapture. Exercise gives us a sense of accomplishment and mastery, tires us out, and improves our sleep in a way that reading, listening to a podcast, and enjoying music don’t. In fairness to the rest-and-relaxation lobby, some introspection is indeed good for you, and being able to tolerate idleness and boredom is a sign of psychological strength. I’m a clinical psychiatrist, and I know well that self-understanding is a cherished goal of therapy. But too much self-examination doesn’t make you happier or more enlightened. Besides, vacation is not the time to work on that skill. You can incorporate moments of idleness into your daily life if you want to get better at sitting with yourself, but vacation is a time for feeling good and escaping responsibilities, including the ones to yourself. Accordingly, you should do what makes you feel good, and that’s activity, not idleness. This advice might sound heretical coming from a shrink, but in fact, it’s informed by my experience with patients. I spend a lot of time trying to get depressed and anxious people to stop their unproductive navel-gazing and engage with the outside world and other people. One former patient who was determined to have a relaxing vacation in Italy rented a villa, sat around the pool with a pile of books all day, and promptly descended into a state of anxious misery. When he emailed me about his predicament, I told him to get up and go hiking with his wife every day. He returned from his trip two weeks later having barely read a book, but very relaxed and happy. He’d spent nearly all his time outside, hiking and eating. The psychological benefits of exertion don’t apply just to vacations; they’re for everyone at any time. My father-in-law, an 86-year-old with a ferocious intellectual appetite, never seems so happy and vividly alive as he does after a brief spin around the neighborhood on his recumbent bike. But taking on a physical challenge during vacation is especially valuable. You are guaranteed to have a lot of downtime while you’re away, which is a lure for idleness, mind-wandering, and unhappiness—all of which can be remedied by exercise. You also have far more time for exertion during vacation than in regular life, so you can really get into the zone and enjoy yourself. I don’t want you to think that the psychological benefits of an active vacation require you to travel far, buy fancy equipment, or put in Herculean effort. You don’t have to bike 40 miles a day or hike from sunrise to sundown. Perhaps you could try taking a long, vigorous walk each morning of your trip or commit to stretching for 30 minutes a day. All that matters is that your exertion exceeds your normal baseline physical activity enough to command your attention. Breathe hard enough that you can forget the mountain views around you or the cool ocean breeze, and you might just find that you’ll forget your worries too. from https://ift.tt/iPkUt5S Check out http://natthash.tumblr.com At first, it was all very exciting. In 1971, a team of Danish researchers stationed on Greenland’s northwest coast found that a local Inuit community had remarkably low levels of diabetes and heart disease. The reason, the researchers surmised, was their high-marine-fat diet—in other words, fish oil. Incidence of heart disease, which once afflicted relatively few Americans, had shot up since the turn of the century, and here, seemingly, was a simple solution. “I remember how exciting those studies were when they first came out,” Marion Nestle, a professor emerita of nutrition and food studies at NYU, told me. “The idea that there were populations of people who were eating fish and were protected against heart disease looked fabulous.” The hype didn’t stop with heart disease. Soon, fish oil was being hailed as a panacea. It could help prevent dementia! Depression! Obesity! Cancer! News stories and books parroted these claims. And supplement makers capitalized. By 2014, fish-oil supplements were a billion-dollar industry. Today, the market continues to grow at an astronomical rate. The growth of the science supporting fish oil’s curative properties, meanwhile, has been, shall we say, less astronomical. The early papers that sparked the initial enthusiasm were merely observational, meaning that they could establish only correlation, not causation. When the randomized control trials eventually began to trickle in, the results were mixed at best. Tens of thousands of studies later, things haven’t gotten all that much clearer: We still don’t have anything close to a firm grasp of what fish oil can do and what it cannot. And lately, things have only gotten weirder. Most experts acknowledge that fish oil does have some modest benefits in certain circumstances. Omega-3, its star nutrient, has been shown to lower levels of a fat associated with heart failure, help prevent premature births, and improve infant formulas. But these are a far cry from the game-changing promise of the early studies. That promise, over the years, has gotten lost in a tangle of theoretical possibilities, Nestle told me. Fish oil contains two distinct types of Omega-3, DHA and EPA; maybe only the former is providing the benefit. Or maybe only the latter. Maybe the benefit comes only from pairing the two. Maybe neither does anything unless it’s consumed with other parts of the actual fish. And that’s just the beginning. Maybe the benefits have less to do with fish itself and more to do with the fact that if you’re eating fish, you’re probably not also eating a hamburger or a pork chop. Maybe they have to do with your overall diet. Maybe they don’t have to do with your diet at all. Maybe it’s just that fish eaters tend to be wealthier and, not unrelatedly, healthier in the first place. Maybe it’s something else entirely. Read: [The fishy science of omega-3s] Through much of the 2010s, one fish-oil study after another came up empty, Richard Bazinet, a nutrition researcher at the University of Toronto, told me—“null, null, null, null, null.” And then came REDUCE-IT, a trial funded by the pharmaceutical company Amarin to test its fish-oil-based heart drug, called Vascepa. The results, presented in 2018, found that, among high-risk adults already receiving another type of cholesterol-lowering treatment, the drug decreased the risk of heart failure and other serious cardiovascular events by an eye-popping 25 percent. Fish oil, it seemed, was back in business. When the study’s lead author, the Harvard cardiologist Deepak Bhatt, presented his findings at the American Heart Association’s annual meeting in Chicago, the crowd gave a standing ovation. The following year, the FDA approved the drug for the use studied in REDUCE-IT. (The agency had already approved the drug for a different use back in 2013.) With triumph, though, came controversy. Even at the time of Bhatt’s presentation, some cardiologists noted that the study’s mineral-oil-based placebo—a pill selected because its color and consistency mimic those of fish oil, but whose use in fish-oil studies has been debated—seemed not to be entirely neutral. In fact, the placebo seemed to be harming people. Initially, nothing much came of these concerns. Then, last month, a new analysis published in the journal Circulation substantiated them and then some. It showed, based on elevated levels of several biomarkers in blood-test results, that the placebo may have increased volunteers’ risk of heart attack and stroke. Many researchers found these results to be compelling evidence that Vascepa’s eye-popping success could be due to a bad placebo, not a great drug. “What’s somewhat shocking about that paper is that it looks like everything got worse in the placebo group and the treatment group stayed the same,” Bazinet told me. “You could have given the subjects a glass of water. Anything would have been better against that placebo.” Steven Nissen, a cardiologist at the Cleveland Clinic who was involved in a different Omega-3 trial, called the Circulation study’s findings “extraordinarily disturbing.” Two members of the expert panel that in 2019 recommended that the FDA green-light Vascepa even told Stat’s Matthew Herper that, if they’d had access to the new data at the time, they might not have voted to approve. To make matters more confusing, the Circulation study—as in, the very study that ignited this controversy—was also funded by Amarin, and one of the study’s 13 authors was Bhatt, the lead author on REDUCE-IT. In a statement, Amarin told me it “continues to stand by the results of REDUCE-IT” and is “very surprised” that the panel members would make such comments based on the Circulation paper. The company stressed that REDUCE-IT’s positive results “could not be explained” by the placebo, and that the effects found in the Circulation study were too minor to “correlate to any meaningful changes in outcomes.” Bhatt agreed, telling me he sees the new paper not as undermining REDUCE-IT but simply as clarifying Vascepa’s biological mechanisms. He defended the use of mineral oil as a placebo, arguing that it alone could not explain the significant risk reductions observed in the trial. The lead author of the Circulation study, Paul Ridker, declined to comment on the controversial results. But other experts I spoke with were considerably less sanguine than Bhatt. Several would say only that, at this point, the REDUCE-IT results are basically uninterpretable. Nissen, who has in the past called REDUCE-IT “almost certainly a false-positive study,” went so far as to say that he thinks the benefits it found can be “entirely explained by the harms of the placebo” and that Amarin should have known not to use mineral oil. JoAnn Manson, the chief of preventive medicine at Brigham and Women’s Hospital in Boston and the leader of the largest-ever study of vitamin D and Omega-3 pills in healthy adults, was more sympathetic to the idea that the Circulation study’s findings likely don’t account for the full 25 percent risk reduction. But she also raised the possibility that the Vascepa, if ineffective, could be dangerous: Some studies have shown that a high daily dosage of fish oil can heighten one’s risk of developing a type of irregular heartbeat. (Amarin called the suggestion that Vascepa could be ineffective and dangerous “a gross distortion of fact,” saying that “the findings of independent, thorough, and impartial scientific and statistical reviews” had determined that the drug’s benefits to the at-risk patients for whom it is designed more than make up for its risks.) The upshot of all this is that an already murky situation has become a good deal murkier, and there’s no end to the murk in sight. Which is a shame because, in one sense at least, the stakes are higher now than they’ve been in some time: REDUCE-IT suggested that Vascepa could legitimately save lives. If it can’t, that’s more than a scientific scandal; it’s a real, human loss. “I’ve never seen anything like this,” Bazinet told me. “In a way, it’s not surprising. The field’s been controversial all the time, and now we probably have the biggest controversy.” The only way out of this mess, experts said, is to run a whole new trial comparing Vascepa (or its generic equivalent, icosapent ethyl) with something everyone agrees is a true placebo—one that we can be confident doesn’t harm people. Manson is leading a team applying for NIH funding to run such a study. (She said that Amarin told her it was not open to a replication trial and that the company declined to fund three related studies. When I asked Amarin about this, the company told me it would not replicate REDUCE-IT, because the outcomes “read out robustly,” and that it does not publicly discuss research proposals from third parties.) The study would also investigate a pair of promising leads turned up by her own major study, an ongoing project that has found that although Omega-3 did very little for the population as a whole, it might have considerable benefits for Black people and people who don’t eat much fish. In the meantime, doctors are unlikely to ditch Vascepa, Clifford Rosen, a professor at Tufts University School of Medicine, told me. In the first quarter of 2022, Amarin sold nearly $100 million worth of the drug, which is its only product. “There’s such momentum to use this agent that until the next study comes around, I think there’s still going to be widespread use,” Rosen said. To his point: In 2019, the American Diabetes Association recommended icosapent ethyl for certain patients as part of its official standards of care, based explicitly on the REDUCE-IT results. Since the publication of the Circulation paper, the ADA has made no move to withdraw that recommendation. (When I asked whether the group is considering doing so, its chief scientific and medical officer said only that it had “followed the evidence based on what was available at the time.”) Not that this state of affairs is particularly novel. We’ve known for years that fish-oil supplements have virtually no benefits for your average, healthy person, Pieter Cohen, a professor at Harvard Medical School, told me. That hasn’t stopped tens of millions of Americans from popping the pills every day. “People just love to take supplements,” Rosen said. “It’s religiosity … It’s magical thinking.” Vascepa is an FDA-approved drug, not merely a supplement, but in some ways the line isn’t all that clear. The dosage is certainly higher, the packaging is certainly better, and the regulations are certainly stricter. But if you don’t understand the biological mechanism behind either the drug or the supplement—and scientists do not—that makes it tough to assert with any confidence that they’re fundamentally distinct. “If you don’t know how something works—like you have no idea how it works—it’s hard to say that they’re different!” Bazinet told me. “Because it could just be a little bit more of the same mechanism. It’s not clear.” When it comes to fish oil, very little is. from https://ift.tt/XyfkbBD Check out http://natthash.tumblr.com Seventy-eight days and more than 7,000 documented cases into the United States’s 2022 outbreak of monkeypox, federal officials have declared the disease a nationwide public-health emergency. With COVID-19 (you know, the other ongoing viral public-health emergency) still very much raging, the U.S. is officially in the midst of two infectious-disease crises, and must now, with limited funds, wrangle both at once. The two viruses and diseases are starkly different, as are the demographics of the populations most at risk. But simultaneous outbreaks will compete for overlapping sets of resources, and put a subset of people at especially high peril of contracting both viruses, perhaps even in some cases simultaneously. They will also demand distinct responses, from both the nation’s leaders and the public. For most Americans, today’s declaration changes little: The take-home can be “don’t panic,” says Taison Bell, a critical-care and infectious-disease physician at UVA Health. Avoid stigmatizing men who have sex with men, who remain at greatest risk, but “be aware that everyone is at risk.” Today on a press call HHS Secretary Xavier Becerra urged every American “to take monkeypox seriously and to take responsibility to help us tackle this virus.” The trick will be to do that while ensuring that resources go to those most in need. Although federal officials have repeatedly reassured the public that the country has all the resources it needs to keep the outbreak under control, the nation is clearly not living up to containment potential. Many experts have criticized the country’s relatively timid steps toward action in the outbreak’s early days, when stamping out the virus was, in fact, relatively feasible. Now, as tests, treatments, and vaccines continue to be in short supply and remain difficult to access, allowing case numbers to balloon, the window of opportunity to beat the virus back seems narrower than ever. [Read: America should have been able to handle monkeypox] Today’s declaration will mobilize more resources toward outbreak containment, allowing federal leaders to dole out vaccines and treatments more quickly, and source more data from state and local governments. But perhaps this move has already come too late. In the press briefing, CDC Director Rochelle Walensky noted that about 1.6 million to 1.7 million people in the U.S.—including men who have sex with men who are living with HIV—had been designated as “at highest risk of monkeypox right now,” and should be prioritized for vaccination. That number far exceeds the 600,000 or so doses of the two-shot Jynneos vaccine that have been rolled out nationwide; acquiring and shipping more will still take the U.S. months, stretching into the fal and beyond. In the meantime, federal officials are mulling whether they can split Jynneos doses into five, and administer them intradermally instead of subcutaneously—a “dose sparing” approach. I caught up with Gregg Gonsalves, an epidemiologist and AIDS activist at Yale University, and an adviser to the WHO on the monkeypox outbreak, to make sense of today’s declaration, and the epidemic’s prognosis in the United States. Gonsalves has been a vocal critic of the U.S.’s approach to COVID; in this new outbreak, he and others already see an encore of past failures playing out. Today, Demetre Daskalakis, the White House’s national monkeypox-response deputy coordinator, described the American reaction to monkeypox as “aggressive, responsive, and ongoing since day one.” There is little to suggest that this is true. Our conversation has been edited for clarity and length. Katherine J. Wu: How would you describe the current state of the monkeypox outbreak in the United States? Gregg Gonsalves: We’re not in a good place. We’ve been hearing refrains, similar to COVID, about having all the tools we need to deal with this—enough for all jurisdictions in the U.S. It is patently untrue. We keep seeing mounting cases. We’re likely under-testing. And we certainly have a shortage of vaccines, despite what the secretary says. And so we’re not in a very good position to contain this, which gives us the sad distinction of potentially having two viruses go endemic in the United States over the course of the past three years. Wu: And that’s been clear for some time now—that the outbreak has been ballooning, and that resources are scarce. Should we have declared a public-health emergency sooner? Would that have helped? Gonsalves: A declaration of a public-health emergency gives us some ability to do certain things that ordinarily we can’t. But what’s instructive to me is that we’ve had a public-health emergency for COVID. And two COVID czars! And we were the leaders in COVID deaths per capita among the G7, and now we’re the leaders in absolute numbers of monkeypox cases. So appointing leaders and declaring declarations is one thing. But when you have leaders saying this has been an aggressive response since day one, and this is where we are? That doesn’t make you feel confident in our nation’s response to this new, emerging outbreak. It would be much more useful to say, we got out of the gate slow, but we are now bringing in all relevant federal actors. We are talking with local and state health departments. We are talking with community-based organizations. And we’re going to use all resources of government in a strategic operational campaign to deal with this. Right now, I’m still not sure what their plan is. We’re going to cut the vaccine doses into five pieces? We need research to evaluate that, or think about ACAM2000 [an older smallpox vaccine with more side effects] as a fallback. And there’s still no real articulation of how we’re going to continue to ramp up diagnoses so that we can figure out where lingering cases are. Commercial vendors are now testing, but we’re still mostly in the passive surveillance [phase], where people are coming to sexual-health clinics, their primary-care physicians. How much active testing is going on in the community, working with organizations funded by the Ryan White HIV/AIDS program [which provides resources to low-income people living with HIV], for instance? To get out into gay bars, sex clubs, gay parties, and offering people who might have suspicious lesions or pimples or bumps the privacy of a mobile-health van to get tested, or a referral for testing at a nearby location? Also, you have to be in [isolation] for 21 days with this infection. Many people can’t afford to do that. And some of the men who are catching this are either underinsured or uninsured. And there are still lingering problems with access to [the antiviral] Tpoxx. And there’s no new money coming down the pike. The administration floated the idea that they need $7 billion for a monkeypox response. But for some strange reason, they didn’t tell that to Congress formally before they left on recess. This is an emergency without a budget. So this does not give you the sense that there’s an aggressive response since the beginning. We don’t need to be coddled. Some straight talk would be nice. Wu: How should the public be reacting at this point? The nation has been asked to respond; monkeypox has been categorized similar to COVID, in one sense. And yet, risk levels are so different across populations. What does that mean for us? Gonsalves: My friend Joe Osmundson, a microbiologist, has said, for all the people telling the gay community they should get on the ball, the gay community’s been responding valiantly. And the article that Kai Kupferschidmt wrote today in The New York Times has a message that is really, really important: This is not a gay disease, but it’s happening to men who have sex with men [MSM], and we need to start thinking about how we can address the pandemic ourselves. That’s what happened during the AIDS epidemic. Gay men understood the collective threat to them, and changed sexual behavior. Kai was saying we maybe need to reduce partners, to forgo certain kinds of sexual activities or events until we’re vaccinated, to think of limiting our sexual partners into pods, sort of like the early days of COVID socializing. So I think the gay community is responding well, and they understand the risks. For the general community right now, the possibility of another endemic virus in the United States should worry them. But more out of solidarity and empathy for people in the LGBT community who are facing this, and bearing the brunt of it right now. Could it jump to other populations in which there’s close physical contact? Prisons, homeless shelters, university dormitories and athletic facilities? Potentially. But right now, they should just keep an eye on it. What should concern people is the government’s response. Don’t flip the burden on the American people, again, as we’ve done with COVID—a make-your-own-adventure version of the pandemic. We need the government to deliver, and they haven’t been delivering. It’s been this creaking, bumbling, sclerotic response. And now they put two people in charge, declare a public-health emergency—they have no money—and they’re saying everything’s fine. Wu: Do you think monkeypox has a high likelihood of moving into non-MSM populations, or becoming endemic here in the U.S.? Gonsalves: This has been largely circulating among MSM, and we haven’t seen a lot of jump to household contacts, et cetera. But the longer this persists, the greater the chances for even sporadic cases outside of the context of men who have sex with men. [Read: Squirrels could make monkeypox a forever problem] And there’s a worry that this will also start to follow the fractures in our social geography. For somebody who’s followed the AIDS epidemic for 40 years … even when some people get access to the interventions they need, many people don’t. You could easily see this sort of ending up exactly where HIV is—in the rural South, in communities of Black men who have sex with men, who have some of the highest HIV rates in the world. We could see monkeypox become a disease of marginalized neglected populations, like everything else in the U.S. That’s the biggest fear over the long term. That we’re going to be dealing with this for quite a while, and that it’s going to go to places where there’s less robust public-health or health-care infrastructure, and people have far less access to resources. And so it lingers. Wu: What would a future like that reflect of America’s approach to public health?
from https://ift.tt/Tw93lrf Check out http://natthash.tumblr.com By the time a cell senses that it’s been infected by a virus, it generally knows it is doomed. Soon, it will be busted up by the body’s immunological patrol or detonated by the invader itself. So the moribund cell plays its trump card: It bleats out microscopic shrieks that danger is nigh. These intercellular messages, ferried about by molecules called interferons, serve as a warning signal to nearby cells—“‘You are about to be infected; it’s time for you to set up an antiviral state,’” says Juliet Morrison, an immunologist at UC Riverside. Recipient cells start battening down the hatches, switching on hundreds of genes that help them pump out suites of defensive proteins. Strong, punchy interferon responses are essential to early viral control, acting as a “first line of defense” that comes online within minutes or hours, says Mario Santiago, an immunologist at the University of Colorado Anschutz Medical Campus. At their best, interferons can contain the infection so quickly that the rest of the immune system hardly needs to get involved. Viruses, of course, aren’t content to let that happen. Pretty much all of them, SARS-CoV-2 included, are darn good at impairing interferon signaling, or finding their way around the virus-blocking shields that cells raise after heeding those molecular calls. And as new coronavirus variants arise, they may be steadily improving their ability to resist interferons’ punch—making it easier, perhaps, for the microbes to spread within and between bodies, or spark more serious disease. [Read: How long can the coronavirus keep reinfecting us?] This development may sound kind of familiar: As the coronavirus has evolved, one of its main moves has been to repeatedly dodge the antibodies that vaccines and past infections raise. But there’s a key difference. Although antibodies are powerful, most are able to recognize and latch onto only a super-specific sliver of a single pathogen’s physique. Interferons, meanwhile, are the ultimate generalists, a set of catch-all burglar alarms. Even if the body has never seen a particular pathogen before and no relevant antibodies are present, cells will make interferons as soon as they realize a virus is around—“any and all viruses,” says Eleanor Fish, an immunologist at the University of Toronto. “It doesn’t matter what the virus is, it doesn’t matter where it comes in.” Once warned, interferon-ized cells leap into action. They will reinforce their exteriors; sharpen molecular scissors that can hack the microbe to bits, should it get inside; and conjure up sticky substances that can stop the virus’s progeny from exiting. All that buys the immune system time to rouse, again with interferons’ help, more precise fighters, such as B cells and T cells. But this system isn’t foolproof. Some viruses will cloak their innards from cellular sensors, so the relevant alarm wires never get tripped. Others destroy the gears that get the interferon system cranking, so the warning signals never get sent. Particularly resilient viruses may not even mind if interferon messages go out, because they’re able to steel themselves against the many defenses that the molecules marshal in other cells. Strategies such as these are pretty much ubiquitous because they’re so crucial to pathogen success. “I defy you to identify any virus that doesn’t have in its genome factors to block the interferon response,” Fish told me. This, from our perspective, is not ideal. Derail these early responses, and “there’s a domino effect,” says Vineet Menachery, a coronavirologist at the University of Texas Medical Branch. More cells get infected; antibody and T-cell responses hang back, even as viral particles continue to spread. Eventually, the body may get wise and try to catch up. But by then, it may be too late. The brunt of viral replication might be over, leaving the immune frenzy to misdirect much of its havoc onto our own tissues instead. Interferons, then, can make or break a host’s fate. Researchers have found that people whose interferons are weak or laggy after catching the coronavirus are far more likely to get very seriously sick. Others experience similar problems when their immune system churns out misguided antibodies that attack and destroy interferons as they try to ferry messages among cells. Interferons also play a very dramatic role in counteracting the viruses that cause dengue and yellow fever. Those pathogens are rapidly wrangled by rodent interferons and never make those animals sick, Morrison told me. In people, though, the microbes have cooked up ways to muffle the molecules—a big reason they cause such debilitating and deadly disease. [Read: Could genetics be the key to never getting the coronavirus?] Coronaviruses in general are pros at interferon sabotage. Among the most powerful is MERS, which “just shuts down everything” in the interferon assembly line, says Susan Weiss, a coronavirologist at the University of Pennsylvania. That essentially ensures that almost no interferons are released, even when gobs of virus are roiling about, a dismantling of defenses that likely contributes to MERS’ substantial fatality rate. Weiss doesn’t think SARS-CoV-2 is likely to copy its cousin in that respect anytime soon. The virus does have some ability to gum up interferon production, but it would take a lot more, she told me, to silence the system as MERS has. Still, SARS-CoV-2 seems to be taking its own small, tentative steps toward interferon censorship. For months, several groups of researchers, CU Anschutz’s Santiago among them, have been studying how well the virus can invade and replicate inside of cells that have been exposed to interferons. Recent variants such as Delta and Omicron, they’ve found, seem to be better at infiltrating those reinforced cells compared with some versions that preceded them—a hint that this resistance might be helping new iterations of the virus sweep the globe and cause repeated rounds of disease. The bump in SARS-CoV-2’s resilience doesn’t appear to be massive—more “at the margins” of enhancing infective success, Menachery told me. Antibody evasion, for instance, might be playing the more dominant role in helping the virus spread and sicken more people. Still, the pattern that’s unfolding raises a discomfiting question, Santiago told me. Interferons’ potency against the virus already seems to be getting slowly but surely undermined; “what if at some point in the future, the virus becomes a lot more resistant?” The challenge of managing COVID, whether through vaccines or antivirals, might disproportionately balloon. And unlike antibody evasion, with interferon resistance, “there’s not anything we can do to vaccinate against this,” Menachery told me. [Read: The BA.5 wave is what COVID normal looks like] Still, there’s probably a ceiling to how interferon-resistant the coronavirus can become. Eventually, repeated attempts to disarm our alarm systems may “come at a cost” to the virus’s infective potential, or the speed at which it spreads, Morrison told me. Interferons are also extremely diverse, and have redundancies among them. Should one flavor get flummoxed by a pathogen, another would likely help fill in the gaps. Many researchers, such as Fish, are also testing interferon-based treatments in people who have very recently been infected by or exposed to the coronavirus. Several of these trials have produced mixed or disappointing results. Even so, “I think there’s every reason to think that interferons are still going to be effective” in some form, once scientists nail the timing, recipe, and dose, says Eric Poeschla, Santiago’s collaborator at CU Anschutz. The molecules are, after all, nature’s DIY antivirals.
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