ReportWire

Tag: adverse effects

  • Pfizer Couldn’t Pay for Marketing This Good

    Pfizer Couldn’t Pay for Marketing This Good

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    On June 3, 2021, a roughly 60-year-old man in the riverside city of Magdeburg, Germany, received his first COVID vaccine. He opted for Johnson & Johnson’s shot, popular at that point because unlike Pfizer’s and Moderna’s vaccines, it was one-and-done. But that, evidently, was not what he had in mind. The following month, he got the AstraZeneca vaccine. The month after that, he doubled up on AstraZeneca and added a Pfizer for good measure. Things only accelerated from there: In January 2022, he received at least 49 COVID shots.

    A few months later, employees at a local vaccination center thought to themselves, Huh, wasn’t that guy in here yesterday? and alerted the police. By that point, the German Press Agency reported, the man had been vaccinated as many as 90 times. And still he was not done. As of November, he said he’d received 217 COVID shots—217!

    That’s according to a new paper published in The Lancet. After German researchers learned of the man from newspaper articles, they managed to contact him via the public prosecutor investigating the case. He was “very interested” in participating in a study Kilian Schober, an immunologist at Uniklinikum Erlangen and a co-author on the paper said in a statement. They pieced together his vaccination timeline through interviews and medical records, and collected blood and saliva samples to examine the immunological effects of “hypervaccination.”

    The man’s identity hasn’t been revealed, and in the paper he’s referred to only as “HIM” (seemingly an acronym, though what it stands for is not specified). He is hardly the world’s only hypervaccinated person. A retired postman in India had reportedly received 12 shots by January 2022 and told The New York Times, “I still want more.” A New Zealand man, meanwhile, allegedly racked up 10 in a single day. But pause for a moment and consider the sheer logistics of HIM’s feat. In all, he received his 217 vaccinations over the course of just under two and a half years, which comes out to an average of seven and a half shots a month, although the distribution was far from even. For several weeks in early 2022, he received two shots nearly every day. He seems to have had a strong preference for the Pfizer and Moderna vaccines, but he also got at least one shot of AstraZeneca and Sanofi-GSK and, of course, Johnson & Johnson.

    Why? you might wonder. The paper itself elides this question, saying only that he did so “deliberately and for private reasons.” Perhaps the most obvious explanation would be extreme, probably pathological COVID anxiety. News reports from April 2022 offer another possible explanation: that he did so to sell the vaccination cards. But German prosecutors did not bring charges once HIM’s scheme was uncovered, and he continued getting unnecessary shots.

    Getting 217 COVID shots is very much not the public-health guidance in Germany or anywhere else. Yet the strategy seemingly panned out: HIM has never contracted COVID, researchers concluded based on antigen tests, PCR tests, and bloodwork. “If you ask immunologists, we might have predicted that it would be not beneficial to do this,” Cindy Leifer, an immunologist at Cornell University who wasn’t involved with the Lancet study, told me. They might have expected the constant action to exhaust the immune system, leaving it vulnerable to actual viral threats. But such worries came to nothing.

    Still, immunologists cautioned against inferring any strong causal connection. He avoided the virus; he got vaccinated 217 times. He did not necessarily avoid the virus because he got vaccinated 217 times. In fact, the authors wrote, although hypervaccination seems to have increased the quantity of antibodies and T cells that HIM’s body produced to fend off the virus—even after 216 shots, the 217th still produced a modest increase—it had no real effect on the quality of the immune response. “He would have been just as well protected if he had gotten a normal number of three to four vaccinations,” Schober told me.

    Nor did hypervaccination lead to any adverse effects. By shot 217, one might have expected to see some of the rare side effects associated with the vaccines, such as myocarditis, pericarditis, or Guillain-Barré Syndrome, but as far as researchers could tell, HIM was completely fine. Remarkably, he didn’t even report feeling minor side effects from any of his 217 shots. On some level, this makes total sense: As Schober reasonably pointed out, HIM probably would not have gotten all those shots if each one had knocked him out for a day. Fair, but still: 217 shots and no side effects? How?

    If nothing else, HIM is one hell of an advertisement for the vaccines. Worried about side effects from your third booster? Well, this guy’s gotten more than 200, and he’s a-okay. Travis Kelce has been called Mr. Pfizer, but he’s got nothing on HIM. Scientifically, things are somewhat murkier. The results of the HIM study were largely unsurprising, researchers told me, but the mysteries at the margins—such as the absence of any side effects—are a good reminder that four years after the pandemic began, immunology is still, as my former colleague Ed Yong wrote, “where intuition goes to die.”

    At the end of the paper, the authors are very clear: “We do not endorse hypervaccination as a strategy to enhance adaptive immunity.” The takeaway, Leifer said, should not be the more shots, the better. Schober told me he even tried to personally convey this message to HIM after his 216th shot. “From the bottom of my heart as a medical doctor, I really told him that he shouldn’t get vaccinated again,” Schober said.

    HIM seemed to take this advice seriously. Then he went and got shot No. 217 anyway.

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    Jacob Stern

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  • Older Americans Are About to Lose a Lot of Weight

    Older Americans Are About to Lose a Lot of Weight

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    Imagine an older man goes in to see his doctor. He’s 72 years old and moderately overweight: 5-foot-10, 190 pounds. His blood tests show high levels of triglycerides. Given his BMI—27.3—the man qualifies for taking semaglutide or tirzepatide, two of the wildly popular injectable drugs for diabetes and obesity that have produced dramatic weight loss in clinical trials. So he asks for a prescription, because his 50th college reunion is approaching and he’d like to get back to his freshman-year weight.

    He certainly could use these drugs to lose weight, says Thomas Wadden, a clinical psychologist and obesity researcher at the University of Pennsylvania, who recently laid out this hypothetical in an academic paper. But should he? And what about the tens of millions of Americans 65 and older who aren’t simply trying to slim down for a cocktail party, but live with diagnosable obesity? Should they be on Wegovy or Zepbound?

    Already, seniors make up 26.6 percent of the people who have been prescribed these and other GLP-1 agonists, including Ozempic, since 2018, according to a report from Truveta, which draws data from a large network of health-care systems. In the coming years, that proportion could rise even higher: The bipartisan Treat and Reduce Obesity Act, introduced in Congress last July, would allow Medicare to cover drug treatments for obesity among its roughly 50 million Part D enrollees above the age of 65; in principle, about two-fifths of that number would qualify as patients. Even if this law doesn’t pass (and it’s been introduced half a dozen times since 2012), America’s retirees will continue to be prescribed these drugs for diabetes in enormous numbers, and they’ll be losing weight on them as well. One way or another, the Boomers will be giving shape to our Ozempic Age.

    Economists say the cost to Medicare of giving new drugs for obesity to just a fraction of this aging generation would be staggering—$13.6 billion a year, according to an estimate published in The New England Journal of Medicine last March. But the health effects of such a program might also be unsettling. Until recently, the very notion of prescribing any form of weight loss whatsoever to an elderly patient—i.e., someone 65 or older—was considered suspect, even dangerous. “Advising weight loss in obese older adults is still shunned in the medical community,” the geriatric endocrinologist Dennis Villareal and his co-authors wrote in a 2013 “review of the controversy” for a medical journal. More than a decade later, clinicians are still struggling to reach consensus on safety, Villareal told me.

    Ample research shows that interventions for seniors with obesity can resolve associated complications. Wadden helped run a years-long, randomized trial of dramatic calorie reduction—using liquid meal replacements, in part—and stringent exercise advice for thousands of overweight adults with type 2 diabetes. “Clearly the people who were older did have benefits in terms of improved glycemic control and blood-pressure control,” he told me. Other, smaller studies led by Villareal find that older people who succeed at losing weight through diet and exercise end up feeling more robust.

    Such outcomes are significant on their own terms, says John Batsis, who treats and studies geriatric obesity at the UNC School of Medicine. “When we talk about older adults, we really need to be thinking about what’s important to older adults,” he told me. “It’s for them to be able to get on the floor and play with their grandchildren, or to be able to walk down the hallway without being completely exhausted.” But weight loss can also have adverse effects. When a person addresses their obesity through dieting alone, as much as 25 percent of the weight they lose derives from loss of muscle, bone, and other fat-free tissue. For seniors who, through natural aging, are already near the threshold of developing a functional impairment, a sudden drop like this could be enfeebling. Wadden’s trial found that, among the people who were on the weight-loss program for more than a decade, their risk of fracture to the hip, shoulder, upper arm, or pelvis increased by 39 percent. An analogous increase has turned up in studies of patients who undergo bariatric surgery, Batsis told me.

    The effect of dieting on muscle and bone can be attenuated, but not prevented, through resistance training. And obesity itself—which is associated with higher bone density, but perhaps also reduced bone quality—may pose its own fracture risks, Batsis said. But even when a weight-loss treatment benefits an older patient, what happens when it ends? People tend to regain fat, but they don’t recover bone and muscle, Debra Waters, the director of gerontology research at the University of Otago, in New Zealand, told me. That makes the long-term effects of these interventions for older adults very murky. “What happens when they’re 80? Are they going to have really poor bone quality, and be at higher risk of fracture? We don’t know,” Waters said. “It’s a pretty big gamble to take, in my opinion.”

    Villareal told me that doctors should apply “the general principle of starting slow and going slow” when their older patients are trying to lose weight. But that approach doesn’t necessarily square with the rapid and remarkable weight loss seen in patients who are taking semaglutide or tirzepatide, which may produce a greater proportional loss of muscle and bone. (For semaglutide, it appears to be about 40 percent.)

    Then again, when given to laboratory animals, GLP-1 drugs seem to tamp down inflammation in the brain; and they’re now in clinical trials to see whether they might slow the progression of Alzheimer’s disease and dementia. Their multiple established benefits could also help seniors address several chronic problems—diabetes, obesity, fatty liver disease, and kidney disease, for instance—all at once. “Such a ‘one-stop shop’ approach can lead to reduction of medication burden, adverse drug events, hypoglycemic episodes, medication costs, and treatment nonadherence,” one team of geriatricians proposed in 2019.

    Overall, Batsis remains optimistic. “As a clinician, I’m very excited about these medications,” he told me. As a scientist, though, he’s inclined to wait and see. It’s surely true that some degree of weight loss is a great idea for some older patients. “But the million-dollar question is: What’s the sweet spot? How much weight is really enough? Is it 5 to 10 percent? Or is it 25 percent? We don’t know.” Waters said that if Medicare is going to pay for people’s Wegovy, then it should also cover scans of their body composition, to help predict how weight loss might affect their muscles and bones. Wadden said he thinks that treatments should be limited to people who have specific, weight-related complications. For everyone else—as for the hypothetical 72-year-old man who is prepping for his college reunion—he counsels prudence.

    To some extent, such advice is beside the point. Older people are already on Ozempic, and they’re already on Trulicity, and some of them are already taking GLP-1 drugs as a treatment for obesity. Truveta reported that the patients in its member health-care systems who are over 65 have received 281,000 prescriptions for GLP-1 drugs across the past five years. Given the network’s size, one can assume that at least 1 million seniors, overall, have already tried these medications. Millions more will try them in the years to come. If we still have questions about their use, mass experience will start providing answers.

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    Daniel Engber

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