ReportWire

Tag: risk factors

  • The Enigma of ‘Heat-Related’ Deaths

    The Enigma of ‘Heat-Related’ Deaths

    The autopsy should have been a piece of cake. My patient had a history of widely metastatic cancer, which was pretty straightforward as far as causes of death go. Entering the various body cavities, my colleague and I found what we anticipated: Nearly every organ was riddled with tumors. But after we had completed the work, I realized that I knew why the patient had died, but not why he’d died that day. We found no evidence of a heart attack or blood clot or ruptured bowel. Nothing to explain his sudden demise. Yes, he had advanced cancer—but he’d been living with that cancer the day before he died, and over many weeks and months preceding. I asked my colleague what he thought. Perhaps there had been some subtle change in the patient’s blood chemistry, or in his heart’s electrical signaling, that we simply couldn’t see? “I guess the patient just up and died,” he said.

    I’m a hospital pathologist; my profession is one of many trying to explain the end of life. In that role, I have learned time and again that even the most thorough medical exams leave behind uncertainty. Take the current spate of heat-related fatalities brought on by a summer of record-breaking temperatures. Residents of Phoenix endured a month of consecutive 110-degree days. People have been literally sizzling on sidewalks. And news organizations are taking note of what is said to be a growing body count: 39 heat deaths in Maricopa County, Arizona; 10 in Laredo, Texas. But the precision of these figures is illusory. Cause of death cannot be measured as exactly as the temperature, and what qualifies as “heat-related” will always be a judgment call: Some people die from heat; others just up and die when it happens to be hot.

    Mortality is contested ground, a place where different types of knowledge are in conflict. In Clark County, Nevada, for example, coroners spend weeks investigating possible heat-related deaths. Families are interviewed, death scenes are inspected, and medical tests are performed. The coroner must factor in all of these sources of information because no single autopsy finding can definitively diagnose a heat fatality. A victim may be found to have suffered from hyperthermia—an abnormally high body temperature—or they may be tossed into the more subjective bucket of those who died from ”environmental heat stress.”

    Very few deaths undergo such an extensive forensic examination in the first place. Most of the time, the circumstances appear straightforward—a 75-year-old has a stroke; a smoker succumbs to an exacerbation of his chronic lung disease—and the patient’s primary-care doctor or hospital physician completes the death certificate on their own. But heat silently worsens many preexisting conditions; oppressive temperatures can cause an already dysfunctional organ to fail. A recent study out of China estimated that mortality from heart attacks can rise as much as 74 percent during a severe, several-day heat wave. Another study from the U.S. found that even routine temperature fluctuations can subtly alter kidney function, cholesterol levels, and blood counts. Physicians can’t easily tease out these influences. If an elderly man on a park bench suddenly slouches over from a heart attack in 90-degree weather, it’s hard to say for sure whether the heat was what did him in. Epidemiologists must come to the rescue, using statistics to uncover those hidden causes at the population level. This bird’s-eye view shows a simple fact: Bad weather means more death. But it still doesn’t tell us what to think about the man on the bench.

    Research (and common sense) tells us that some individuals are going to be especially vulnerable to climate risks. Poverty, physical labor, substandard housing, advanced age, and medical comorbidities all put one in greater danger of experiencing heat-related illness. The weather has a way of kicking you while you’re down, and the wealthy and able-bodied are better able to dodge the blows. A financial struggle as small as an unpaid $51 portion of an electricity bill can prove deadly in the summer. In the autopsies I’ve performed, a patient’s family, medical record, and living situation often told a story of long-term social neglect. But there was no place on the death certificate for me to describe these tragic circumstances. There was certainly no checkbox to indicate that climate change contributed to a fatality. Such matters were out of my jurisdiction.

    The public-health approach to assessing deaths has its own problems. Mostly it’s confusing. Reams of scientific studies have reported on hundreds of different risk factors for mortality. Sultry weather appears to be dangerous, but so do skipping breakfast, taking naps, and receiving care from a male doctor. Researchers have declared just about everything a major killer. A few months ago, the surgeon general announced that feeling disconnected is as deadly as smoking up to 15 cigarettes a day. The FDA commissioner has said that misinformation is the nation’s leading cause of premature death. And is poverty or medical error the fourth-leading cause? I can’t keep track.

    With so many mortality statistics at our disposal, which ones get emphasized can be more a matter of politics than science. Liberals see the current heat wave—and its wave of heat-related deaths—as an urgent call to action to combat climate change, while conservatives dismiss this concern as a mental disorder. A recent Wall Street Journal op-ed concluded that worrying about climate change is irrational, because “if heat waves were as deadly as the press proclaims, Homo sapiens couldn’t have survived thousands of years without air conditioning.” (Humans survived thousands of years without penicillin, but syphilis was still a net negative.) Similarly, when COVID became the third-leading cause of death in the U.S., pandemic skeptics said it was a fiction: Victims were dying “with COVID,” not “from COVID.” Because many people who died of SARS-CoV-2 had underlying risk factors, some politicians and doctors brushed off the official numbers as hopelessly confounded. Who could say whether the virus had killed anyone at all?

    The dismissal of COVID’s carnage was mostly cynical and unscientific. But it’s true that death certificates paint one picture of the pandemic, and excess-death calculations paint another. Scientists will be debating COVID’s exact body count for decades. Fatalities from heat are subject to similar ambiguities, even as their determination comes with real-world consequences. In June, for example, officials from Multnomah County, Oregon—where Portland is located—sued oil and gas producers over the effects of a 2021 heat wave that resulted in 69 heat-related deaths, as officially recorded. This statistic will likely be subjected to intense cross-examination. The pandemic showed us that casting doubt on the deceased is a convenient strategy.

    No matter how we count the bodies, extreme weather leads to suffering—especially among the most vulnerable members of society. A lot of people have already perished during this summer’s heat wave. Their passing is more than a coincidence—not all of them just up and died.

    Benjamin Mazer

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  • Being Alive Is Bad for Your Health

    Being Alive Is Bad for Your Health

    In 2016, I gave up Diet Coke. This was no small adjustment. I was born and raised in suburban Atlanta, home to the Coca-Cola Company’s global headquarters, and I had never lived in a home without Diet Coke stocked in the refrigerator at all times. Every morning in high school, I’d slam one with breakfast, and then I’d make sure to shove some quarters (a simpler time) in my back pocket to use in the school’s vending machines. When I moved into my freshman college dorm, the first thing I did was stock my mini fridge with cans. A few years later, my then-boyfriend swathed two 12-packs in wrapping paper and put them under his Christmas tree. It was a joke, but it wasn’t.

    You’d think quitting would have been agonizing. To my surprise, it was easy. For years, I’d heard anecdotes about people who forsook diet drinks and felt their health improve seemingly overnight—better sleep, better skin, better energy. I’d also heard whispers about the larger suspected dangers of fake sweeteners. Yet I’d loved my DCs too much to be swayed. Then I tried my first can of unsweetened seltzer at a friend’s apartment. After years of turning my nose up at the thought of LaCroix, I realized that much of what I enjoyed about Diet Coke was its frigidity and fizz. That was enough. I switched to seltzer on the spot, prepared to join the smug converted and receive whatever health benefits were sure to accrue to me for my good behavior.

    Except they never came. Seven years later, I feel no better than I ever did drinking four or five cans of the stuff a day. I still stick to seltzer anyway—because, you know, who knows?—and I’ve mostly forgotten that Diet Coke exists. But the diet sodas had not, as it turns out, been preventing me from getting great sleep or calming my rosacea or feeling, I don’t know, zesty. Besides the caffeine, they appeared to make no difference in how good or bad I felt at all.

    Yesterday, Reuters reported that the WHO’s International Agency for Research on Cancer will soon declare aspartame, the sweetener used in Diet Coke and many other no-calorie sodas, as “possibly carcinogenic to humans.” I probably should have felt vindicated. I may not feel better now, but many years down the road (knock on wood), I’ll be better off. I’d bet on the right horse! Instead, I felt nothing so much as irritation. Over the past few decades, a growing number of foods and behaviors have become the regular subject of vague, ever-changing health warnings—fake sweeteners, real sugar, wine, butter, milk (dairy and non), carbohydrates, coffee, fat, chocolate, eggs, meat, veganism, vegetarianism, weightlifting, drinking a lot of water, and scores of others. The more warnings there are, the less actionable any particular one of them feels. What, exactly, is anyone supposed to do with any of this information, except feel bad about the things they enjoy?

    It’s worth reviewing what is actually known or suspected about diet sodas and health. The lion’s share of research on this topic happens in what are known as observational studies—scientists track consumption and record health outcomes, looking for commonalities and trends linking behavior and effects. These studies can’t tell you if the behavior caused the outcome, but they can establish an association that’s worth investigating further. Regular, sustained diet-soda consumption has been linked to weight gain, Type 2 diabetes, and increased risk of stroke, among other things—understandably troublesome correlations for people worried about their health. But there’s a huge complicating factor in understanding what that means: For decades, advertisements recommended that people who were already worried about—or already had—some of those same health concerns substitute diet drinks for those with real sugar, and many such people still make those substitutions in order to adhere to low-carb diets or even out their blood sugar. As a result, little evidence suggests that diet soda is solely responsible for any of those issues—health is a highly complicated, multifactorial phenomenon in almost every aspect—but many experts still recommend limiting your consumption of diet soda as a reasonable precaution.

    A representative for the IARC would neither confirm nor deny the nature of the WHO’s pending announcement on aspartame, which will be released on July 14. For the sake of argument, let’s assume that Reuters’s reporting is correct: In two weeks, the organization will update the sweetener’s designation to indicate that it’s “possibly carcinogenic.” To regular people, those words—especially in the context of a health organization’s public bulletins—would seem to imply significant suspicion of real danger. The evidence may not yet all be in place, but surely there’s enough reason to believe that the threat is real, that there’s cause to spook the general public.

    Except, as my colleague Ed Yong wrote in 2015, when the IARC made a similar announcement about the carcinogenic potential of meat, that’s not what the classification means at all. The IARC chops risk up into four categories: carcinogenic (Group 1), probably carcinogenic (Group 2A), possibly carcinogenic (Group 2B), and unclassified (Group 3). Those categories do one very specific thing: They describe how definitive the agency believes the evidence is for any level of increased risk, even a very tiny one. The category in which aspartame may soon find itself, 2B, makes no grand claims about carcinogenicity. “In practice, 2B becomes a giant dumping ground for all the risk factors that IARC has considered, and could neither confirm nor fully discount as carcinogens. Which is to say: most things,” Yong wrote. “It’s a bloated category, essentially one big epidemiological shruggie.”

    The categories are not at all intended to communicate the degree of the risk involved—just how sure or unsure the organization is that there’s a risk associated with a thing or substance at all. And association can mean a lot of things. Hypothetically, regular consumption of food that may quadruple your risk of a highly deadly cancer would fall in the same category as something that may increase your risk of a cancer with a 95 percent survival rate by just a few percentage points, as long as the IARC felt similarly confident in the evidence for both of those effects.

    These designations about carcinogenicity are just one example of how health information can arrive to the general public in ways that are functionally useless, even if well intentioned. Earlier this year, the WHO advised against all use of artificial sweeteners. At first, that might sound dire. But the actual substance of the warning was about the limited evidence that those sweeteners aid in weight loss, not any new evidence about their unique ability to harm your health in some way. (The warning did nod to the links between long-term use of artificial sweeteners and increased risks of cardiovascular disease, Type 2 diabetes, and premature death, but as the WHO noted at the time, these are understood as murky correlations, not part of an alarming breakthrough discovery.)

    The same release quotes the WHO’s director for nutrition and food safety advising that, for long-term weight control, people need to find ways beyond artificial sweeteners to reduce their consumption of real sugar—in essence, it’s not a health alert about any particular chemical, but about dessert as a concept. How much of any sweetener would you need to cut out of your diet in order to limit any risks it may pose? The release, on its own, doesn’t specify. Consider a birthday crudités platter instead of a cake, just to be sure. (Is that celery non-GMO? Organic? Just checking.)

    The media, surely, deserve our fair share of blame for how quickly and how far these oversimplified ideas spread. Many people are very worried about the food they eat—perhaps because they have received so many conflicting indicators over the years about how that food affects their bodies—and flock to news that something has been deemed beneficial or dangerous. At best, the research that many such stories cite is rarely definitive, and at worst, it’s so poorly designed or otherwise flawed that it’s flatly incapable of producing useful information.

    Taken in aggregate, this morass of poor communication and confusing information has the very real potential to exhaust people’s ability to identify and respond to actual risk, or to confuse them into nihilism. The solution-free finger-wagging, so often about the exact things that many people experience as the little joys in everyday life, doesn’t help. When everything is an ambiguously urgent health risk, it very quickly begins to feel like nothing is. I still drink a few Diet Cokes a year, and I maintain that there’s no better beverage to pair with pizza. We’re all going to die someday.

    Amanda Mull

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  • The Future of Long COVID

    The Future of Long COVID

    In the early spring of 2020, the condition we now call long COVID didn’t have a name, much less a large community of patient advocates. For the most part, clinicians dismissed its symptoms, and researchers focused on SARS-CoV-2 infections’ short-term effects. Now, as the pandemic approaches the end of its third winter in the Northern Hemisphere, the chronic toll of the coronavirus is much more familiar. Long COVID has been acknowledged by prominent experts, national leaders, and the World Health Organization; the National Institutes of Health has set up a billion-dollar research program to understand how and in whom its symptoms unfurl. Hundreds of long-COVID clinics now freckle the American landscape, offering services in nearly every state; and recent data hint that well-vetted drugs to treat or prevent long COVID may someday be widespread. Long COVID and the people battling it are commanding more respect, says Hannah Davis, a co-founder of the Patient-Led Research Collaborative, who has had long COVID for nearly three years: Finally, many people “seem willing to understand.”

    But for all the ground that’s been gained, the road ahead is arduous. Long COVID still lacks a universal clinical definition and a standard diagnosis protocol; there’s no consensus on its prevalence, or even what symptoms fall under its purview. Although experts now agree that long COVID does not refer to a single illness, but rather is an umbrella term, like cancer, they disagree on the number of subtypes that fall within it and how, exactly, each might manifest. Some risk factors—among them, a COVID hospitalization, female sex, and certain preexisting medical conditions—have been identified, but researchers are still trying to identify others amid fluctuating population immunity and the endless slog of viral variants. And for people who have long COVID now, or might develop it soon, the interventions are still scant. To this day, “when someone asks me, ‘How can I not get long COVID?’ I can still only say, ‘Don’t get COVID,’” says David Putrino, a neuroscientist and physical therapist who leads a long-COVID rehabilitation clinic at Mount Sinai’s Icahn School of Medicine.

    As the world turns its gaze away from the coronavirus pandemic, with country after country declaring the virus “endemic” and allowing crisis-caliber interventions to lapse, long-COVID researchers, patients, and activists worry that even past progress could be undone. The momentum of the past three years now feels bittersweet, they told me, in that it represents what the community might lose. Experts can’t yet say whether the number of long-haulers will continue to increase, or offer a definitive prognosis for those who have been battling the condition for months or years. All that’s clear right now is that, despite America’s current stance on the coronavirus, long COVID is far from being beaten.


    Despite an influx of resources into long-COVID research in recent months, data on the condition’s current reach remain a mess—and scientists still can’t fully quantify its risks.

    Recent evidence from two long-term surveys have hinted that the pool of long-haulers might be shrinking, even as new infection rates remain sky-high: Earlier this month, the United Kingdom’s Office for National Statistics released data showing that 2 million people self-reported lingering symptoms at the very start of 2023, down from 2.3 million in August 2022. The U.S. CDC’s Household Pulse Survey, another study based on self-reporting, also recorded a small drop in long-COVID prevalence in the same time frame, from about 7.5 percent of all American adults to roughly 6. Against the massive number of infections that have continued to slam both countries in the pandemic’s third year and beyond, these surveys might seem to imply that long-haulers are leaving the pool faster than newcomers are arriving.

    Experts cautioned, however, that there are plenty of reasons to treat these patterns carefully—and to not assume that the trends will be sustained. It’s certainly better that these data aren’t showing a sustained, dramatic uptick in long-COVID cases. But that doesn’t mean the situation is improving. Throughout the pandemic, the size of the long-COVID pool has contracted or expanded for only two reasons: a change in the rate at which people enter, or at which they exit. Both figures are likely to be in constant flux, as surges of infections come and go, masking habits change, and vaccine and antiviral uptake fluctuates. Davis pointed out that the slight downward tick in both studies captured just a half-year stretch, so the downward slope could be one small portion of an undulating wave. A few hours spent at the beach while the tide is going out wouldn’t be enough to prove that the ocean is drying up.

    Recent counts of new long-COVID cases might also be undercounts, as testing slows and people encounter more challenges getting diagnosed. That said, it’s still possible that, on a case-by-case basis, the likelihood of any individual developing long COVID after a SARS-CoV-2 infection may have fallen since the pandemic’s start, says Deepti Gurdasani, a clinical epidemiologist at Queen Mary University of London and the University of New South Wales. Population immunity—especially acquired via vaccination—has, over the past three years, better steeled people’s bodies against the virus, and strong evidence supports the notion that vaccines can moderately reduce the risk of developing long COVID. Treatments and behavioral interventions that have become more commonplace may have chipped away at incidence as well. Antivirals can now help to corral the virus early in infection; ventilation, distancing, and masks—when they’re used—can trim the amount of virus that infiltrates the body. And if overall exposure to the virus can influence the likelihood of developing long COVID, that could help explain why so many debilitating cases arose at the very start of the pandemic, when interventions were few and far between, says Steven Deeks, a physician researcher at UC San Francisco.

    There’s not much comfort to derive from those individual-level stats, though, when considering what’s happening on broader scales. Even if immunity makes the average infected person less likely to fall into the long-COVID pool, so many people have been catching the virus that the inbound rate still feels like a flood. “The level of infection in many countries has gone up substantially since 2021,” Gurdasani told me. The majority of long-COVID cases arise after mild infections, the sort for which our immune defenses fade most rapidly. Now that masking and physical distancing have fallen by the wayside, people may be getting exposed to higher viral doses than they were a year or two ago. In absolute terms, then, the number of people entering the long-COVID pool may not really be decreasing. Even if the pool were getting slightly smaller, its size would still be staggering, an ocean of patients with titanic needs. “Anecdotally, we still have an enormous waitlist to get into our clinic,” Putrino told me.

    Deeks told me that he’s seen another possible reason for optimism: People with newer cases of long COVID might be experiencing less debilitating or faster-improving disease, based on what he’s seen. “The worst cases we’ve seen come from the first wave in 2020,” he said. But Putrino isn’t so sure. “If you put an Omicron long-COVID patient in front of me, versus one from the first wave, I wouldn’t be able to tell you who was who,” he said. The two cases would also be difficult to compare, because they’re separated by so much time. Long COVID’s symptoms can wax, wane, and qualitatively change; a couple of years into the future, some long-haulers who’ve just developed the condition may be in a spot that’s similar to where many veterans with the condition are now.

    Experts’ understanding of how often people depart the long-COVID pool is also meager. Some long-haulers have undoubtedly seen improvement—but without clear lines distinguishing short COVID from medium and long COVID, entry and exit into these various groups is easy to over- or underestimate. What few data exist on the likelihood of recovery or remission is inconsistent, and not always rosy: Investigators of RECOVER, a large national study of long COVID, have calculated that about two-thirds of the long-haulers in their cohort do not return to baseline health. Putrino, who has worked with hundreds of long-haulers since the pandemic began, estimates that although most of his patients experience at least some benefit from a few months of rehabilitation, only about one-fifth to one-quarter of them eventually reach the point of feeling about as well as they did before catching the virus, while the majority hit a middling plateau. A small minority of the people he has treated, he told me, never seem to improve at all.

    Letícia Soares, a long-hauler in Brazil who caught the virus near the start of the pandemic, falls into that final category. Once a disease ecologist who studied parasite transmission in birds, she is now mostly housebound, working when she is able as a researcher for the Patient-Led Research Collaborative. Her days revolve around medications and behavioral modifications she uses for her fatigue, sleeplessness, and chronic pain. Soares no longer has the capacity to cook or frequently venture outside. And she has resigned herself to this status quo until the treatment landscape changes drastically. It is not the life she pictured for herself, Soares told me. “Sometimes I think the person I used to be died in April of 2020.”

    Even long-haulers who have noticed an improvement in their symptoms are wary of overconfidence. Some absolutely do experience what could be called recovery—but for others, the term has gotten loaded, almost a jinx. “If the question is, ‘Are you doing the things you were doing in 2019?’ the answer is largely no,” says JD Davids, a chronic-illness advocate based in New York. For some, he told me, “getting better” has been more defined by a resetting of expectations than a return to good health. Relapses are also not uncommon, especially after repeat encounters with the virus. Lisa McCorkell, a long-hauler and a co-founder of the Patient-Led Research Collaborative, has felt her symptoms partly abate since she first fell ill in the spring of 2020. But, she told me, she suspects that her condition is more likely to deteriorate than further improve—partly because of “how easy it is to get reinfected now.”


    Last week, in his State of the Union address, President Joe Biden told the American public that “we have broken COVID’s grip on us.” Highlighting the declines in the rates of COVID deaths, the millions of lives saved, and the importance of remembering the more than 1 million lost, Biden reminded the nation of what was to come: “Soon we’ll end the public-health emergency.”

    When the U.S.’s state of emergency was declared nearly three years ago, as hospitals were overrun and morgues overflowed, the focus was on severe, short-term disease. Perhaps in that sense, the emergency is close to being over, Deeks told me. But long COVID, though slower to command attention, has since become its own emergency, never formally declared; for the millions of Americans who have been affected by the condition, their relationship with the virus does not yet seem to be in a better place.

    Even with many more health-care providers clued into long COVID’s ills, the waiting lists for rehabilitation and treatment remain untenable, Hannah Davis told me. “I consider myself someone who gets exceptional care compared to other people,” she said. “And still, I hear from my doctor every nine or 10 months.” Calling a wrap on COVID’s “emergency” phase could worsen that already skewed supply-demand ratio. Changes to the nation’s funding tactics could strip resources—among them, access to telehealth; Medicaid coverage; and affordable antivirals, tests, and vaccines—from vulnerable populations, including people of color, that aren’t getting their needs met even as things stand, McCorkell told me. And as clinicians internalize the message that the coronavirus has largely been addressed, attention to its chronic impacts may dwindle. At least one of the country’s long-COVID clinics has, in recent months, announced plans to close, and Davis worries that more could follow soon.

    Scientists researching long COVID are also expecting new challenges. Reduced access to testing will complicate efforts to figure out how many people are developing the condition, and who’s most at risk. Should researchers turn their scientific focus away from studying causes and cures for long COVID when the emergency declaration lifts, Davids and others worry that there will be ripple effects on the scientific community’s interest in other, neglected chronic illnesses, such as ME/CFS (myalgic encephalomyelitis or chronic fatigue syndrome), a diagnosis that many long-haulers have also received.

    The end of the U.S.’s official crisis mode on COVID could stymie research in other ways as well. At Johns Hopkins University, the infectious-disease epidemiologists Priya Duggal, Shruti Mehta, and Bryan Lau have been running a large study to better understand the conditions and circumstances that lead to long COVID, and how symptoms evolve over time. In the past two years, they have gathered online survey data from thousands of people who both have and haven’t been infected, and who have and haven’t seen their symptoms rapidly resolve. But as of late, they’ve been struggling to recruit enough people who caught the virus and didn’t feel their symptoms linger. “I think that the people who are suffering from long COVID will always do their best to participate,” Duggal told me. That may not be the case for individuals whose experiences with the virus were brief. A lot of them “are completely over it,” Duggal said. “Their life has moved on.”

    Kate Porter, a Massachusetts-based marketing director, told me that she worries about her family’s future, should long COVID fade from the national discourse. She and her teenage daughter both caught the virus in the spring of 2020, and went on to develop chronic symptoms; their experience with the disease isn’t yet over. “Just because the emergency declaration is expiring, that doesn’t mean that suddenly people are magically going to get better and this issue is going to go away,” Porter told me. After months of relative improvement, her daughter is now fighting prolonged bouts of fatigue that are affecting her school life—and Porter isn’t sure how receptive people will be to her explanations, should their illnesses persist for years to come. “Two years from now, how am I going to explain, ‘Well, this is from COVID, five years ago’?” she said.

    A condition that was once mired in skepticism, scorn, and gaslighting, long COVID now has recognition—but empathy for long-haulers could yet experience a backslide. Nisreen Alwan, a public-health researcher at the University of Southampton, in the U.K., and her colleagues have found that many long-haulers still worry about disclosing their condition, fearing that it could jeopardize their employment, social interactions, and more. Long COVID could soon be slated to become just one of many neglected chronic diseases, poorly understood and rarely discussed.

    Davis doesn’t think that marginalization is inevitable. Her reasoning is grim: Other chronic illnesses have been easier to push to the sidelines, she said, on account of their smaller clinical footprint, but the pool of long-haulers is enormous—comprising millions of people in the U.S. alone. “I think it’s going to be impossible to ignore,” she told me. One way or another, the world will have no choice but to look.

    Katherine J. Wu

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  • COVID Vaccines Are Turning Into Flu Shots

    COVID Vaccines Are Turning Into Flu Shots

    For all the legwork that public-health experts have done over the past few years to quash comparisons between COVID-19 and the flu, there sure seems to be a lot of effort nowadays to equate the two. In an advisory meeting convened earlier today, the FDA signaled its intention to start doling out COVID vaccines just like flu shots: once a year in autumn, for just about everyone, ad infinitum. Whatever the brand, primary-series shots and boosters (which might no longer be called “boosters”) will guard against the same variants, making them interchangeable. Doses will no longer be counted numerically. “This will be a fundamental transition,” says Jason Schwartz, a vaccine policy expert at Yale—the biggest change to the COVID-vaccination regimen since it debuted.

    Hints of the annual approach have been dropping, not so subtly, for years. Even in the spring of 2021, Pfizer’s CEO was floating the idea of yearly shots; Peter Marks, the director of the FDA’s Center for Biologics Evaluation and Research, teased it throughout 2022. This past September, Joe Biden officially endorsed it as “a new phase in our COVID-19 response,” and Ashish Jha, the White House’s COVID czar, memorably highlighted the convenience of combining a flu shot and a COVID shot into a single appointment: “I really believe this is why God gave us two arms.”

    Still, in today’s meeting, FDA officials were pushier than ever in their advocacy for the flu-ification of COVID vaccines. “We think that simplification of the vaccination regimen would contribute to easier vaccine deployment, better communication, and improved vaccine coverage,” Jerry Weir, the FDA’s director of the division of viral products, said at the meeting. The timing is important: After renewing the U.S.’s pandemic-emergency declaration earlier this month, the Biden administration seems set to allow its expiration this coming April. That makes the present moment awfully convenient for repackaging a chaotic, crisis-caliber vaccination paradigm as a scheduled, seasonal, normal-seeming one. A once-a-year strategy, modeled on a routine recommendation, suggests that “we’re no longer in emergency mode,” says Maria Sundaram, a vaccine researcher at the Marshfield Clinic Research Institute. Or at least, that’s the message that the public is likely to hear.

    But federal regulators may be trying to fit a COVID-shaped peg into a flu-shaped hole. The experts I spoke with largely agreed: Eventually, someday, annual autumn shots for COVID “will probably be sufficient,” says Gregory Poland, a vaccinologist at Mayo Clinic. “Are we ready for that yet? I’m not sure that’s the case at all.”

    Even in the short term, COVID-vaccination tactics need a revamp. “It’s clear above all that the current approach isn’t working,” Schwartz told me. Despite abundant supply, demand for COVID boosters in the U.S. has been abysmal—and interest seems to be declining with each additional dose. Last fall’s bivalent shot has reached the arms of only 15 percent of Americans; even among adults over 65—a majority of whom sign up for flu shots each fall—the vaccination rate hasn’t yet reached 40 percent.

    For most of the time that COVID shots have been around, figuring out when to get them has been a hassle, with different guidelines and requirements that depend on age, sex, risk factors, vaccination history, and more. Pharmacies have had to stock an absurd number of vials and syringes to accommodate the various combinations of brands and dose sizes; record-keeping on flimsy paper cards has been a total joke. “I do this for a living, and I can barely keep track,” Schwartz said. Recommendations on the proper timing and number of doses have also changed so many times that many Americans have simply checked out. After the bivalent recipe debuted, polls found that an alarming proportion of people didn’t even know the shot was available to them.

    Streamlining COVID-vaccine recommendations will remove a lot of that headache, Sundaram told me. Most people would need to keep only one mantra in mind—one dose, each fall—and could top off their flu and COVID immunity at the same time. Burdens on pharmacies and clinics would be lower, and communication would be far easier—a change that could make an especially big difference for those with children, among whom COVID-vaccine uptake has been the lowest. “It’ll be more scheduled, more systematic,” says Charlotte Hobbs, a pediatric infectious-disease specialist at the University of Mississippi Medical Center. COVID shots could simply be offered at annual well-child visits, she told me. “It’s something we already know works well.”

    The advantages of a flu-ified COVID shot aren’t just about convenience. If we have to shoehorn COVID vaccines into an existing paradigm, Sundaram told me, influenza’s is the best candidate. SARS-CoV-2, like the flu, is excellent at altering itself to dodge our defenses; it spreads readily in winter; and our immunity to infection tends to fade rather quickly. All of that adds up to a need for regularly updated shots. Such a system has been in place for decades for the flu: At the end of each winter, a panel of experts convenes to select the strains that should be targeted by the next formulation; manufacturers spend the next several months whipping up big batches in time for an autumn-ish rollout. The pipeline depends on a global surveillance system for flu viruses, as well as regular surveys of antibody levels in the community to suss out which strains people are still protected against. The premise has been so well vetted by now that researchers can skip the chore of running large-scale clinical trials to determine the efficacy and safety of each new, updated recipe.

    But a seasonal strategy works best for a seasonal virus—and SARS-CoV-2 just isn’t there yet, says Hana El Sahly, an infectious-disease physician at Baylor College of Medicine. Though flu viruses tend to hop between the globe’s hemispheres, alternately troubling the north and the south during their respective cold months, this new coronavirus has yet to confine its spread to one part of the calendar. (Marks, of the FDA, tried to address this concern at today’s meeting, asserting that “we’re starting to see some seasonality” and that fall was indeed the very sensible for an annual rollout.) SARS-CoV-2 has also been spitting out concerning variants and subvariants at a faster rate than the flu (and flu shots already have a hard time keeping up with evolution). The FDA’s new proposal suggests picking SARS-CoV-2 variants in June to have a vaccine ready by September, a shorter timeline than is used for flu. That still might not be fast enough: “By the time we detect a variant, it will have ripped through the global population and, in a few more weeks, died down,” El Sahly told me. The world got a preview of this problem with last year’s bivalent shot, which overlapped with the dominance of its target subvariants for only a couple of months. A flu model for COVID would make more sense “if we had stable, predictable dynamics,” says Avnika Amin, a vaccine epidemiologist at Emory University. “I don’t think we’re at that point.”

    Murkiness around vaccine effectiveness makes this transition complicated too. Experts told me that it’s gotten much more difficult to tell how well our COVID vaccines are working, and for how long, fueling debates over how often they should be given and how often their composition should change. Many people have now been infected by the virus multiple times, which can muddy calculations of vaccine effectiveness; better treatments also alter risk profiles. And many researchers told me they’re concerned that the data shortcuts we use for flu—measures of antibodies as a proxy for immune protection—just won’t fly for COVID shots. “We need better clinical data,” El Sahly told me. In their absence, the hasty adoption of a flu framework could lead to our updating and distributing COVID shots too often, or not often enough.

    A flu-ish approach also wouldn’t fix all of the COVID vaccines’ problems. Today’s discussion suggested that, even if a new COVID-shot strategy change goes through, officials will still need to recommend several different dose sizes for several different age groups—a more complex regimen than flu’s—and may advise additional injections for those at highest risk. At the same time, COVID shots would continue to be more of a target for misinformation campaigns than many other vaccines and, at least in the case of mRNA-based injections, more likely to cause annoying side effects. These issues and others have driven down interest—and simply pivoting to the flu paradigm “is not going to solve the uptake problem,” says Angela Shen, a vaccine-policy expert at Children’s Hospital of Philadelphia.

    Perhaps the greatest risk of making COVID vaccines more like flu shots is that it could lead to more complacency. In making the influenza paradigm a model, we also threaten to make it a ceiling. Although flu shots are an essential, lifesaving public-health tool, they are by no means the best-performing vaccines in our roster. Their timeline is slow and inefficient; as a result, the formulations don’t always match circulating strains. Already, with COVID, the world has struggled to chase variants with vaccines that simply cannot keep up. If we move too quickly to the fine-but-flawed framework for flu, experts told me, it could disincentivize research into more durable, more variant-proof, less side-effect-causing COVID shots. Uptake of flu vaccines has never been stellar, either: Just half of Americans sign up for the shots each year—and despite years of valiant efforts, “we still haven’t figured out how to consistently improve that,” Amin told me.

    Whenever the COVID-emergency declaration expires, vaccination will almost certainly have to change. Access to shots may be imperiled for tens of millions of uninsured Americans; local public-health departments may end up with even fewer resources for vaccine outreach. A flu model might offer some improvements over the status quo. But if the downsides outweigh the pluses, Poland told me, that could add to the erosion of public trust. Either way, it might warp attitudes toward this coronavirus in ways that can’t be reversed. At multiple points during today’s meeting, FDA officials emphasized that COVID is not the flu. They’re right: COVID is not the flu and never will be. But vaccines can sometimes become a lens through which we view the dangers they fight. By equating our frontline responses to these viruses, the U.S. risks sending the wrong message—that they carry equal threat.

    Katherine J. Wu

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  • Pandemic Babies’ Microbiomes Are Bound to Be Different

    Pandemic Babies’ Microbiomes Are Bound to Be Different

    In the spring of 2021, Brett Finlay, a microbiologist at the University of British Columbia, offered the world a bold and worrying prediction. “My guess is that five years from now we are going to see a bolus of kids with asthma and obesity,” he told Wired. Those children, he said, would be “the COVID kids”: those born just before or during the height of the crisis, when the coronavirus was everywhere, and we cleaned everything because we didn’t want it to be.

    Finlay’s forecast isn’t unfounded. As James Hamblin wrote in The Atlantic last year, our health relies on a constant discourse with trillions of microbes that live on or inside our bodies. The members of the so-called microbiome are crucial for digesting our food, training the immune system, even greasing the wheels of cognitive function; there does not seem to be a bodily system that these tiny tenants do not in some way affect. These microbe-human dialogues begin in infancy, and the first three or so years of life are absolutely pivotal: Bacteria must colonize babies, then the two parties need to get into physiological sync. Major disruptions during this time “can throw the system out of whack,” says Katherine Amato, a biological anthropologist at Northwestern University, and raise a kid’s risk of developing allergies, asthma, obesity, and other chronic conditions later in life.

    The earlier, more intense, and more prolonged the interruptions, the worse. Infants who receive heavy courses of antibiotics—which can nuke microbial diversity—are at greater risk of developing such problems; the same is roughly true for babies who are born by C-section, who formula feed, or who grow up in nature-poor environments. If pandemic-era mitigations re-create even an echo of those effects, that could spell trouble for a whole lot of little kids who may have lost out on beneficial microbes in the ongoing effort to keep nasty ones at bay.

    More than a year and a half after Finlay’s original prediction, children are back in day care and school. People no longer keep their distance or avoid big crowds. Even hygiene theater is (mostly) on the wane. And if the wave of respiratory viral illness now slamming much of the Northern Hemisphere is any indication, microbes are once again swirling between tiny hands and mouths. But for the circa-COVID kids, the specter of 2026 and Finlay’s anticipated chronic-illness “bump” still looms—and it’ll be a good while yet before researchers have clarity on just how much of a difference those months of relative microbial emptiness truly made.

    For now, “we are in the realm of speculation,” says Maria Gloria Dominguez Bello, a microbiologist at Rutgers. Scientists don’t understand how, or even which, behaviors may affect the composition of our inner flora throughout our life span. Chronic illnesses such as obesity and asthma also take time to manifest. There’s not yet evidence that they’re on the rise among children, and even if they were, researchers wouldn’t expect to see the signal for at least a couple of years, perhaps more.

    Finlay, for one, stands by his original prediction that the pandemic will bring a net microbiome negative. “We underwent a massive societal shift,” he told me. “I am sure we will see an effect.” And he is not the only one who thinks so. “I think it’s almost inevitable that there has been an impact,” says Graham Rook, a medical microbiologist at University College London. If the middle of this decade passes without incident, Rook told me, “I would be very surprised.” Other researchers, though, aren’t so sure. “I don’t think we have doomed a generation of kids,” says Melissa Manus, an anthropologist and microbiome researcher at the University of Manitoba. A few scientists are even pondering whether the pandemic’s ripple effects may have buoyed the microbiomes of the COVID kids. Martin Blaser, a microbiologist at Rutgers University, told me that, “with any luck,” rates of asthma and obesity might even dip in the next few years.

    When it comes to the pandemic’s potential fallout, researchers agree on just one thing: COVID babies undoubtedly had an unusual infancy; on average, their microbiomes are bound to look quite different. Different, though, isn’t necessarily bad. “It’s not like there is one golden microbiome,” says Efrem Lim, a microbiologist at Arizona State University. Take Liz Johnson’s sons, born in March 2018, August 2020, and March 2022. All three were born vaginally, in the same hospital, with the assistance of the same midwife; all of them then breastfed; and none of them has undergone an early, concerning antibiotic course. And still, “they all started off with different microbiomes,” she told me. (As a microbiome researcher at Cornell focused on infant nutrition, Johnson can check.)

    That’s probably totally fine. Across the human population, microbiomes are known to vary wildly: People can carry hundreds of bacterial species on and inside their bodies, with potentially zero overlap from one individual to the next. Bacterial communities aren’t unlike recipes—if you don’t have one ingredient on hand, another can usually take its place.

    Johnson’s middle son, Lucas, had a starkly different birth experience from that of his older brother—even, in many ways, from that of his younger brother. Lucas was born into a delivery room full of masked faces. In the days after his arrival, no family members came to visit him in the hospital. And although his brothers spent several of their early months jet-setting all around the world with their mother for work trips, Lucas stayed put. “Hardly anybody even knew he was born,” Johnson told me. But throughout his first two years, Lucas still breastfed and had plenty of contact with his family at home, as well as with other kids at day care; he romped in green spaces galore. Yet Johnson and others can’t say, precisely, whether all of that outweighs the sanitariness and the uncrowdedness of Lucas’s earliest days. There would have been a cost to both overcaution and under-caution, “so we just tried to balance everything,” Johnson said. When it comes down to it, scientists just don’t know how much microbial exposure constitutes enough.

    Among COVID babies, microbiome mileage will probably vary, depending on what decisions their parents made at the height of the pandemic—which itself hinges on the sorts of financial and social resources they had. Amato worries most about the families that may have packaged a bunch of sanitizing behaviors together with more established cullers of microbiome diversity: C-sections, formula-feeding, and antibiotic use. Meghan Azad, an infant-health researcher at the University of Manitoba, told me that some new parents might have found it far tougher to breastfeed during the pandemic’s worst—a time when in-person counseling resources were harder to access, and employment was in flux. Chronically poor diets and stress, which many people experienced these past few years, can also chip away at microbiome health.

    Part of the problem is that many of these risk factors, Rook told me, will disproportionately coalesce among people of lower socioeconomic status, who already tend to have less diverse microbiomes. “I worry this will further increase the health disparity between the rich and the poor,” he said. Even SARS-CoV-2 infections themselves, which have continued to concentrate among essential workers and in crowded living settings, appear to alter the microbiome—a shift that may be temporary in adults, but potentially less so in infants, whose microbiomes haven’t yet matured into a stable state.

    Many families exist in a gray zone. Maybe they bleached their households often, but found it easier to breastfeed and cook healthful meals while working from home. Maybe their kids weren’t mingling with tons of other toddlers at day care, but they spent much more time rolling around in the backyard, coated in their pandemic puppy’s drool. If all of those factors feed into an equation that sums up to healthy or not, scientists can’t yet do the math. They’re still figuring out how to appropriately weigh each component, and how to identify others they’ve missed.

    Even in the absence of extra outdoorsiness or dog slobber, Lim isn’t very concerned about the behavioral mitigations people picked up. We’re all “exposed to thousands of microbes all the time,” Lim, who has a 1-and-a-half-year-old daughter, told me. Some extra hand-washing, masking, and time at home is nothing compared with, say, an antibiotic blitzkrieg. Even kids who stayed pretty cloistered “were not living in a bubble.” Some of the social sacrifices kids made may even have strange silver linings. Children no longer attending day care or preschool might have skirted a whole slew of other viral infections that would otherwise have gotten them inappropriate and microbiome-damaging antibiotics prescriptions. Antibiotic use in outpatient settings dropped substantially in 2020, compared with the prior year. Stacked up against the relatively minor toll of pandemic mitigations, Blaser told me, the plus of avoiding antibiotics might just win out. When antibiotic use declines, for example, so do asthma rates.

    Finlay and others are still keeping an eye out for signals that might start to appear in the next few years. Perhaps most at risk are kids whose families went into “hyper-hygiene mode” in the first couple months of their life, when microbes are crucial for properly calibrating the immune system’s anti-pathogen alarms. Miss out on those opportunities, and our body’s defensive cells might end up mistaking enemies for allies, or vice versa, sparking particularly severe infections or autoimmune disease. Once wired into a developing child, Finlay said, such changes might be difficult to reverse, especially for the youngest of the COVID cohort. But other experts are hopeful that certain microbial losses can still be recouped through some combination of diet, outdoor play, and socialization (with people who aren’t sick)—restorative interventions that, ideally, happen as early as possible. “The sooner we fix it, the better,” Blaser said.

    No one can choose precisely which microbes to be exposed to: Tactics that halt the transmission of known pathogens have a way of halting the transmission of benign bugs too. But context matters. It’s possible for microbe-inviting behaviors, such as outdoor play, to coexist alongside microbe-shunning tactics, such as ventilating indoor spaces when there’s a massive respiratory outbreak. The fact that we can influence microbial colonization at all is powerful. During the pandemic, mitigations that kept COVID at bay also cratered rates of flu and RSV. Now that those viruses are back, experts are pointing out that we already know how they can once again be stopped. And the choices that people made, and continue to make, to protect their families from pathogens shouldn’t be viewed as some harmful mistake, says Ariangela Kozik, a microbiologist at the University of Michigan.

    Pandemic kids can get on board with that concept too. Kozik’s now-7-year-old son was a toddler when the pandemic began; even amid society’s hygiene craze, he learned the joys of tumbling around in the dirt and playing with the family’s two dogs. “We talk about how not all germs are the same,” Kozik told me. Her son also picked up and maintained an infection-quashing habit that makes his mom proud: Every day, when he comes home from school, he makes a beeline for the sink to wash his hands. “It’s the first thing he does,” Kozik told me, “even without being asked.”

    Katherine J. Wu

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