Paxlovid is a paradoxlovid. The game-changing antiviral swooped in during the pandemic’s worst winter with the promise of slowing COVID deaths to a trickle. But since it became widely available this spring, death rates have hardly budged.
According to the White House, the problem is not the drug but the fact that too few people are taking it. A recent CDC report found that from April to July, less than one-third of America’s 80-plus-year-olds with COVID ended up taking Paxlovid, even though they had the most to gain from doing so. What gives? Some Americans may be having trouble accessing Paxlovid, but clearly, a significant proportion of patients and doctors are just saying no to antiviral drugs. There are no national statistics on Paxlovid refusal, so I talked with physicians around the country to learn more about their motivations. Who are the anti-Paxxers, and how dangerous is their dogma?
First things first: Paxlovid hesitancy does seem to be political, but that’s not the whole story. As a rule, fewer prescriptions of the drug are given out per capita in red states than in blue ones: Wyoming, for example, appears to be the nation’s leading anti-Paxxer state, with just one course of treatment given out for every 125 residents; in Rhode Island, the most Pax-enthusiastic state, it’s one in 28. (I’m using courses of treatment per capita rather than per COVID case because of the general unreliability of case data these days and differences in testing and reporting practices among states.)
Still, clinicians working in deep-red parts of the country told me that, on this matter at least, their patients are not significantly divided by politics. “Republicans and Democrats both love Paxlovid,” says Jason Bronner, the medical director of primary care at St. Luke’s Medical System, in Idaho. Some 20 to 30 percent of his COVID patients decline to take the drug, he told me, but they don’t appear to be driven by the same polarized attitudes he sees around vaccines. Jessica Kalender-Rich, a geriatrician at the University of Kansas Health System, told me that she still gets occasional requests for ivermectin, and that some of her patients insist that COVID is a hoax. But the ones who outright refuse Paxlovid are not obsessing over microchips or government overreach. Instead, they mostly tell her that they’re worried about treatment side effects and rebound infections of the virus.
Rebound COVID came up again and again when I asked doctors why their patients are hesitant to take Paxlovid. The link between the drug and a return of symptoms after an initial recovery has been the subject of much concern and debate since the spring; just last week, researchers reported in a study that has not yet been peer-reviewed that symptom rebound is more than twice as common among Paxlovid takers than among those who decline it. The fact that so many prominent figures in the federal government—including President Joe Biden, First Lady Jill Biden, CDC Director Rochelle Walensky, and White House Chief Medical Adviser Anthony Fauci—have now had rebound certainly doesn’t help inspire confidence. One of Kalender-Rich’s patients specifically cited Fauci’s experience when refusing the drug. (The next day, the patient felt worse and accepted a prescription.)
Rebound may not be dangerous, but you have to admit that it doesn’t sound like a good time. “People will say, ‘I’d rather be really sick for four or five days than just kind of sick for two weeks,’” says Adam Fiterstein, the chief of urgent care at the New York medical network ProHealth. The threat of rebound might be especially scary for geriatric patients and their family, because it means spending more time alone. “For some of these older adults, that isolation time is actually way worse than the virus at this point in the pandemic,” Kalender-Rich said. Paxlovid mouth—a bitter, metallic taste that can last throughout the course of treatment—can also be a concern for the elderly, who may already suffer from lack of appetite or other issues that restrict their eating.
Drug interactions are another source of worry for the anti-Paxxers. Official COVID-treatment guidelines warn that the antiviral may have ill effects when combined with any of more than 100 other medications. Geriatric patients in particular might need to tweak their daily regimens of pills while under treatment with Paxlovid, Kalender-Rich told me. That’s hardly ever a problem medically, she said, but some people are still reluctant to make the change, especially if a previous doctor told them to never, ever skip a dose.
These potential downsides are extra salient for people who don’t fear COVID like they used to. The patients who refuse Paxlovid are the ones who are doing well, Bronner said: “They don’t feel totally sick and are not scared like they were in previous waves.” Hundreds of Americans are still dying daily from COVID, but any given community might have seen only a handful of severe cases and deaths since the spring. Many patients “don’t feel like they need to take a medicine, because their neighbor was fine,” Kalender-Rich said.
Doctors too can be anti-Paxxers. Hans Duvefelt, a primary-care physician in rural Maine, won’t prescribe Paxlovid to his patients. He told me via email that he avoids it on account of rebound risk, side effects, kidney concerns, and drug interactions. “Paxlovid is an inferior choice,” he said, when compared with molnupiravir, another COVID antiviral. To be clear, the data hold that molnupiravir is less effective than Paxlovid at preventing hospitalization and death. Also, a June preprint found that patients treated with molnupiravir rebounded at least as often as those treated with Paxlovid. Duvefelt did not respond to follow-up questions, so I couldn’t ask him about these data.
Other doctors believe in the good Paxlovid can do but still struggle with the decision to prescribe. “This is a much more nuanced risk-benefit discussion than giving somebody amoxicillin for strep throat,” Jeremy Cauwels, the chief physician at Sanford Health in South Dakota, told me. “If you’re looking at that as an ER doctor, who by definition has no follow-up with the patient, it’s very hard to say, ‘I’m going to give you a drug that interacts with lots of medications.’” Persistent uncertainty about exactly how much Paxlovid helps people who are up to date on their COVID shots doesn’t help.
Regardless of what’s causing Paxlovid hesitancy, the exact stakes are difficult to define. Last month, Ashish Jha, the Biden administration’s COVID-19 response coordinator, told The New York Times that daily deaths from the pandemic could drop by almost 90 percent if every COVID patient over the age of 50 were treated with Paxlovid or monoclonal antibodies. The doctors I spoke with mostly didn’t dispute this; Kalender-Rich said she “would believe a number closer to 75 percent” but agreed with the general sentiment. That said, none of the doctors I spoke with could point me toward any specific cases where one of their patients refused Paxlovid only to end up severely ill or dead. And no one knows how many deaths could be reduced specifically by attacking anti-Paxxer beliefs as opposed to, say, removing barriers to access and encouraging more testing.
Because anti-Paxxerism appears to be less organized and ideological than anti-vaxxerism, some favored strategies to combat the latter—targeting influencers on social media, for example—might not work. The doctors I spoke with said that the best venue for changing minds is the exam room. “It really comes down to a face-to-face conversation” about the risks and benefits of the drug, Cauwels said: “Our patients still trust us enough to have that conversation.”
Pax-hesitant providers, on the other hand, may just need a bit more time to feel convinced that the drug is safe and effective when used correctly; some may be waiting on more data from large, randomized clinical trials. “Across different parts of the country, adoption of new things is always going to be slower,” Kalender-Rich said. That’s not exactly a comforting thought when hundreds of people are still dying every day, but it does suggest, at the very least, that we have something to look forward to.