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Tag: antiviral Paxlovid

  • Life Is Worse for Older People Now

    Life Is Worse for Older People Now

    Last December, during a Christmas Eve celebration with my in-laws in California, I observed what I now realize was the future of COVID for older people. As everyone crowded around the bagna cauda, a hot dipping sauce shared like fondue, it was clear that we, as a family, had implicitly agreed that the pandemic was over. Our nonagenarian relatives were not taking any precautions, nor was anyone else taking precautions to protect them. Endive spear in hand, I squeezed myself in between my 94-year-old grandfather-in-law and his spry 99-year-old sister and dug into the dip.

    We all knew that older people bore the brunt of COVID, but the concerns seemed like a relic from earlier in the pandemic. The brutal biology of this disease meant that they disproportionately have fallen sick, been hospitalized, and died. Americans over 65 make up 17 percent of the U.S. population, but they have accounted for three-quarters of all COVID deaths. As the death count among older people began to rise in 2020, “a lot of my patients were really concerned that they were being exposed without anyone really caring about them,” Sharon Brangman, a geriatrician at SUNY Upstate University Hospital, told me.

    But even now, three years into the pandemic, older people are still in a precarious position. While many Americans can tune out COVID and easily fend off an infection when it strikes, older adults continue to face real threats from the illness in the minutiae of their daily life: grocery trips, family gatherings, birthday parties, coffee dates. That is true even with the protective power of several shots and the broader retreat of the virus. “There is substantial risk, even if you’ve gotten all the vaccines,” Bernard Black, a law professor at Northwestern University who studies health policy, told me. More than 300 people still die from COVID each day, and the overwhelming majority of them are older. People ages 65 and up are currently hospitalized at nearly 11 times the rate of adults under 50.

    Compounding this sickness are all the ways that, COVID aside, this pandemic has changed life for older adults. Enduring severe isolation and ongoing caregiver shortages, they have been disproportionately harmed by the past few years. Not all of them have experienced the pandemic in the same way. Americans of retirement age, 65 and older, are a huge population encompassing a range of incomes, health statuses, living situations, and racial backgrounds. Nevertheless, by virtue of their age alone, they live with a new reality: one in which life has become more dangerous—and in many ways worse—than it was before COVID.

    The pandemic was destined to come after older Americans. Their immune systems tend to be weaker, making it harder for them to fight off an infection, and they are more likely to have comorbidities, which further increases their risk of severe illness. The precarity that many of them already faced going into 2020—poverty, social isolation and loneliness, inadequate personal care—left them poorly equipped for the arrival of the novel coronavirus. More than 1 million people lived in nursing homes, many of which were densely packed and short on staff when COVID tore through them.

    A major reason older people are still at risk is that vaccines can’t entirely compensate for their immune systems. A study recently published in the journal Vaccines showed that for vaccinated adults ages 60 and over, the risk of dying from COVID versus other natural causes jumped from 11 percent to 34 percent within a year of completing their primary shot series. A booster dose brings the risk back down, but other research shows that it wears off too. A booster is a basic precaution, but “not one that everyone is taking,” Black, a co-author of the study, told me. Booster uptake among older Americans for the reengineered “bivalent” shots is the highest of all age groups, but still, nearly 60 percent have not gotten one.

    For every COVID death, many more older people develop serious illness. Risk increases with age, and people older than 70 “have a substantially higher rate of hospitalizations” than those ages 60 to 69, Caitlin Rivers, an epidemiologist at Johns Hopkins University, told me. Unlike younger people, most of whom fully recover from a bout with COVID, a return to baseline health is less guaranteed for older adults. In one study, 32 percent of adults over 65 were diagnosed with symptoms that lasted well beyond their COVID infection. Persistent coughs, aches, and joint pain can linger long after serious illness, together with indirect impacts such as loss of muscle strength and flexibility, which can affect older people’s ability to be independent, Rivers said. Older COVID survivors may also have a higher risk of cognitive decline. In some cases, these ailments could be part of long COVID, which may be more prevalent in older people.

    Certainly, some older adults are able to make a full recovery. Brangman said she has “old and frail” geriatric patients who bounced back after flu-like symptoms, and younger ones who still experience weakness and fatigue. Still, these are not promising odds. The antiviral Paxlovid was supposed to help blunt the wave of old people falling sick and ending up in the hospital—and it can reduce severe disease by 50 to 90 percent. But unfortunately, it is not widely used; as of July, just a third of Americans 80 or older took Paxlovid.

    The reality is that as long as the virus continues to be prevalent, older Americans will face these potential outcomes every time they leave their home. That doesn’t mean they will barricade themselves indoors, or that they even should. Still, “every decision that we make now is weighing that balance between risk and socialization,” Brangman said.

    Long before the pandemic, the threat of illness was already very real for older people.  Where America has landed is hardly a new way of life but rather one that is simply more onerous. “One way to think about it is that this is a new risk that’s out there” alongside other natural causes of death, such as diabetes and heart failure, Black said. But it’s a risk older Americans can’t ignore, especially as the country has dropped all COVID precautions. Since Christmas Eve, I have felt uneasy about how readily I normalized putting so little effort into protecting my nonagenarian loved ones, despite knowing what might happen if they got sick. For older people, who must contend with the peril of attending similar gatherings, “there’s sort of no good choice,” Black said. “The world has changed.”

    But this new post-pandemic reality also includes insidious effects on older people that aren’t directly related to COVID itself. Those who put off nonemergency visits to the doctor earlier in the pandemic, for example, risked worsening their existing health conditions. The first year of the pandemic plunged nearly everyone into isolation, but being alone created problems for older adults that still persist. Before the pandemic, the association between loneliness and higher mortality rates, increased cardiovascular risks, and dementia among older adults was already well established. Increased isolation during COVID amplified this association.

    The consequences of isolation were especially profound for older adults with physical limitations, Naoko Muramatsu, a community-health professor at the University of Illinois at Chicago, told me. When caregivers or family members were unable to visit, people who required assistance for even the smallest tasks, such as fetching the mail and getting dressed, had no options. “If you don’t walk around and if you don’t do anything, we can expect that cognitive function will decline,” Muramatsu said; she has observed this firsthand in her research. One Chinese American woman, interviewed in a survey of older adults living alone with cognitive impairment during the pandemic, described the debilitating effect of sitting at home all day.“I am so useless now,” she told the interviewer. “I am confused so often. I forget things.”

    Even older adults who have weathered the direct and indirect effects of the pandemic still face other challenges that COVID has exacerbated. Many have long relied on personal caregivers or the staff at nursing facilities. These workers, already scarce before the pandemic, are even more so now because many quit or were affected by COVID themselves. “Long-term care has been in a crisis situation for a long time, but it’s even worse now,” Muramatsu said, noting that many home care workers are older adults themselves. Nursing homes nationwide now have nearly 200,000 fewer employees compared with March 2020, which is especially concerning as the proportion of Americans over age 65 explodes.

    Older people won’t have one single approach to contending with this sad reality. “Everybody is trying to figure out what is the best way to function, to try to have some level of everyday life and activity, but also keep your risk of getting sick as low as possible,” Brangman said. Some of her patients are still opting to be cautious, while others consider this moment their “only chance to see grandchildren or concerts or go to family gatherings.” Either way, older Americans will have to wrestle with these decisions without so many of their peers who have died from COVID.

    Again, many of these people did not have it great before the pandemic, even if the rest of the country wasn’t paying attention. “We often don’t provide the basic social support that older people need,” Kenneth Covinsky, a clinician-researcher at the UCSF Division of Geriatrics, said. Rather, ageism, the willful ignorance or indifference to the needs of older people, is baked into American life. It is perhaps the main reason older adults were so badly affected by the pandemic in the first place, as illustrated by the delayed introduction of safety precautions in nursing homes and the blithe acceptance of COVID deaths among older adults. If Americans couldn’t bring themselves to care at any point over the past three years, will they ever?

    Yasmin Tayag

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  • Trying to Stop Long COVID Before It Even Starts

    Trying to Stop Long COVID Before It Even Starts

    Three years into the global fight against SARS-CoV-2, the arsenal to combat long COVID remains depressingly bare. Being vaccinated seems to reduce people’s chances of developing the condition, but the only surefire option for avoiding long COVID is to avoid catching the coronavirus at all—a proposition that feels ever more improbable. For anyone who is newly infected, “we don’t have any interventions that are known to work,” says Akiko Iwasaki, an immunologist and long-COVID researcher at Yale.

    Some researchers are hopeful that the forecast might shift soon. A pair of recent preprint studies, both now under review for publication in scientific journals, hint that two long-COVID-preventing pills might already be on our pharmacy shelves: the antiviral Paxlovid and metformin, an affordable drug commonly used for treating type 2 diabetes. When taken early in infection, each seems to at least modestly trim the chance of developing long COVID—by 42 percent, in the case of metformin. Neither set of results is a slam dunk. The Paxlovid findings did not come out of a clinical trial, and were focused on patients at high risk of developing severe, acute COVID; the metformin data did come out of a clinical trial, but the study was small. When I called more than half a dozen infectious-disease experts to discuss them, all used hopeful, but guarded, language: The results are “promising,” “intriguing”; they “warrant further investigation.”

    At this point, though, any advance at all feels momentous. Long COVID remains the pandemic’s biggest unknown: Researchers still can’t even agree on its prevalence or the features that define it. What is clear is that millions of people in the United States alone, and countless more worldwide, have experienced some form of it, and more are expected to join them. “We’ve already seen early data, and we’ll continue to see data, that that will emphasize the impact that long COVID has on our society, on quality of life, on productivity, on our health system and medical expenditures,” says Susanna Naggie, an infectious-disease physician and COVID-drug researcher at Duke University. “This needs to be a high priority,” she told me. Researchers have to trim long COVID incidence as much as possible, as soon as possible, with whatever safe, effective options they can.

    By now, news of the inertia around preventive long-COVID therapies may not come as much of a shock. Interventions that stop disease from developing are, on the whole, a neglected group; big, blinded, placebo-controlled clinical trials—the industry gold standard—usually look to investigate potential treatments, rather than drugs that might keep future illness at bay. It’s a bias that makes research easier and faster; it’s a core part of the American medical culture’s reactive approach to health.

    Read: Long COVID has forced a reckoning for one of medicine’s most neglected diseases

    For long COVID, the terrain is even rougher. Researchers are best able to address prevention when they understand a disease’s triggers, the source of its symptoms, and who’s most at risk. That intel provides a road map, pointing them toward specific bodily systems and interventions. The potential causes of COVID, though, remain murky, says Adrian Hernandez, a cardiologist and clinical researcher at Duke. Years of research have shown that the condition is quite likely to comprise a cluster of diverse syndromes with different triggers and prognoses, more like a category (e.g., “cancer”) than a singular disease. If that’s the case, then a single preventive treatment shouldn’t be expected to cut its rates for everyone. Without a universal way to define and diagnose the condition, researchers can’t easily design trials, either. Endpoints such as hospitalization and death tend to be binary and countable. Long COVID operates in shades of gray.

    Still, some scientists might be making headway with vetted antiviral drugs, already known to slash the risk of developing severe COVID-19. A subset of long-COVID cases could be caused by bits of virus that linger in the body, prompting the immune system to wage an extended war; a drug that clears the microbe more quickly might lower the chances that any part of the invader sticks around. Paxlovid, which interferes with SARS-CoV-2’s ability to copy itself inside of our cells, fits that bill. “The idea here is really nipping it in the bud,” says Ziyad Al-Aly, a clinical epidemiologist and long-COVID researcher at Washington University in St. Louis, who led the recent Paxlovid work.

    Paxlovid has yet to hit the scientific jackpot: proof from a big clinical trial that shows it can prevent long COVID in newly infected people. But Al-Aly’s study, which pored over the electronic medical records of more than 56,000 high-risk patients, offers some early optimism. People who took the pills, he and his colleagues found, were 26 percent less likely to report lingering symptoms three months after their symptoms began than those who didn’t.

    Read: Inside the mind of an anti-Paxxer

    The pills’ main benefit remains the prevention of severe, acute disease. (In the recent study, Paxlovid-takers were also 30 percent less likely to be hospitalized and 48 percent less likely to die.) Al-Aly expects that the drug’s effectiveness at preventing long COVID—if it’s confirmed in other populations—will be “modest, not huge.” Though the two functions could yet be linked: Some long-COVID cases may result from severe infections that damage tissues so badly that the body struggles to recover. And should Paxlovid’s potential pan out, it could help build the case for testing other SARS-CoV-2 antivirals. Al-Aly and his colleagues are currently working on a similar study into molnupiravir. “The early results are encouraging,” he told me, though “not as robust as Paxlovid.” (Another study, run by other researchers, that followed hospitalized COVID patients found those who took remdesivir were less likely to get long COVID, but a later randomized clinical trial didn’t bear that out.)

    A clinical trial testing Paxlovid’s preventive potency against long COVID is still needed. Kit Longley, a spokesperson for Pfizer, told me in an email that the company doesn’t currently have one planned, though it is “continuing to monitor data from our clinical studies and real-world evidence.” (The company is collaborating with a research group at Stanford to study Paxlovid in new clinical contexts, but they’re looking at whether the pills  might treat long COVID that’s already developed. The RECOVER trial, a large NIH-funded study on long COVID, is also focusing its current studies on treatment.) But given the meager uptake rates for Paxlovid even among those in high-risk groups, Al-Aly thinks his new data could already serve a useful purpose: providing people with extra motivation to take the drug.

    The case for adding metformin to the anti-COVID tool kit might be a bit muddier. The drug isn’t the most intuitive medication to deploy against a respiratory virus, and despite its widespread use among diabetics, its exact effects on the body remain nebulous, says Stacey Schultz-Cherry, a virologist at St. Jude Children’s Research Hospital. But there are many reasons to believe it might be useful. Some research has shown that metformin can mess with the manufacture of viral proteins inside of human cells, Bramante told me, which may impede the ability of SARS-CoV-2 and other pathogens to reproduce. The drug also appears to rev up the disease-dueling powers of certain immune cells, and to stave off inflammation. Studies have shown that metformin can improve responses to certain vaccinations in humans and rodents, and researchers have found that people taking the drug seem less likely to get seriously sick from influenza. Even the diabetes-coronavirus connection may not be so tenuous: Metabolic disease is a risk factor for severe COVID; infection itself can put blood-sugar levels on the fritz. It’s certainly plausible that having a metabolically altered body, Schultz-Cherry told me, could make infections worse.

    Read: The promising treatment we’re not even trying for long COVID

    But the evidence that metformin helps prevent long COVID remains sparse. Carolyn Bramante, the scientist who led the metformin study, told me that when her team first set out in 2020 to investigate the drug’s effects on SARS-CoV-2 infections in a randomized, clinical trial, long COVID wasn’t really on their radar. Like many others in their field, they were hoping to repurpose established medicines to keep infected people out of the hospital; early studies of metformin—as well as the two other drugs in their trial, the antidepressant fluvoxamine and the antiparasitic ivermectin—hinted that they’d work. Ironically, two years later, their story flipped around. A large analysis, published last summer, showed that none of the three drugs were stellar at preventing severe COVID in the short term—a disappointing result (though Bramante contends that their data still indicate that metformin does some good). Then, when Bramante and her colleagues examined their data again, they found that study participants that had taken metformin for two weeks around the start of their illness were 42 percent less likely to have a long-COVID diagnosis from their doctor nearly a year down the road. David Boulware, an infectious-disease physician who helped lead the work, considers that degree of reduction pretty decent: “Is it 100 percent? No,” he told me. “But it’s better than zero.”

    Metformin may well prove to prevent long COVID but not acute, severe COVID (or vice versa). Plenty of people who never spend time in the hospital can still end up developing chronic symptoms. And Iwasaki points out that the demographics of long-haulers and people who get severe COVID don’t really overlap; the latter skew older and male. In the future, early-infection regimens may be multipronged: antivirals, partnered with metabolic drugs, in the hopes of keeping symptoms both mild and short-lived.

    But researchers are still a long way off from delivering that reality. It’s not yet clear, for instance, whether the drugs work additively when combined, Boulware told me. Nor is it a given that they’ll work across different demographics—age, vaccination status, risk factors, and more. Bramante and Boulware’s study cast a decently wide net: Although everyone enrolled in the trial was overweight or obese, many were young and healthy; a few were even pregnant. The study was not enormous, though—about 1,000 people. It also relied on patients’ individual doctors to deliver long-COVID diagnoses, likely leading to some inconsistencies, so other studies that follow up in the future could find different results. For now, this isn’t enough to “mean we should run out and use metformin,” Schultz-Cherry, who has been battling long COVID herself, told me.

    Other medications could still fill the long-COVID gaps. Hernandez, the Duke cardiologist, is hopeful that one of his ongoing clinical trials, ACTIV-6, might provide answers soon. He and his team are testing whether any of several drugs—including ivermectin, fluvoxamine, the steroid fluticasone, and, as a new addition, the anti-inflammatory montelukast—might cut down on severe, short-term COVID. But Hernandez and his colleagues, Naggie among them, appended a check-in at the 90-day mark, when they’ll be asking their patients whether they’re experiencing a dozen or so symptoms that could hint at a chronic syndrome.

    That check-in questionnaire won’t capture the full list of long-COVID symptoms, now more than 200 strong. Still, the three-month benchmark could give them a sense of where to keep looking, and for how long. Hernandez, Naggie, and their colleagues are considering whether to extend their follow-up period to six months, maybe farther. The need for long-COVID prevention, after all, will only grow as the total infection count does. “We’re not going to get rid of long COVID anytime soon,” Iwasaki told me. “The more we can prevent onset, the better off we are.”

    Katherine J. Wu

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