When David Boulware read in 2020 that a cheap and plentiful drug called ivermectin had shown some promise in treating COVID-19, he was eager to study it. Vaccines were slowly being rolled out in the United States, but COVID scientists knew it would be a while before they were available in the rest of the world, where worrisome variants were already beginning to circulate. The University of Minnesota physician and infectious disease researcher had seen a few small but encouraging studies on the drug, which was most often used by vets to treat parasites in horses and sheep (and sometimes lice and scabies in people). Boulware, who specializes in running clinical trials, set up the study early in 2021 with a methodology considered to be the gold standard: the randomized controlled trial, where one group of patients receives the drug, and the other gets a placebo.
In May, Boulware’s team put the word out about the study, aiming to recruit 1,100 volunteers. But then something strange happened: He began receiving hostile emails and messages on Twitter from people who fervently believed that ivermectin was a miracle cure for COVID-19 and that administering a placebo to some trial participants was therefore unethical. “Are you a reembodied NAZI Josef Mengele?” wrote one in an email. “WHAT ARE YOU THINKING? Eliminate your plan to abuse people as needless controls. You have a duty of care.”
Boulware was stunned. In decades of running similar trials for diseases including HIV/AIDS and tuberculosis, he had never received any feedback from strangers, let alone hate mail. But as all things COVID-19 seem to have become politicized, so too has clinical research. There is a growing divide between people who believe the key to ending the pandemic is in preventive measures—vaccines, masks, and distancing—and those who favor treatments. Clearly, these two public health approaches should not be mutually exclusive, but somehow in the current climate, they are. Angela Reiersen, a clinical researcher who is studying potential COVID treatments at Washington University in St. Louis, has seen this pattern play out on her own Twitter feed. “If I post something about vaccines as positive, then I will have a lot of people jumping on that and attacking me, and it’s these people who are all pro early treatment,” she told me. When she tweets good news about potential treatments, on the other hand, she has noticed that she provokes the ire of vaccine advocates. “They kind of seem to suppress any information about early treatment,” she said, “maybe because they feel like it’s going to make people think they don’t need to be vaccinated.”
Often, but not always, the divide is partisan, with the left on Team Prevention and the right on Team Treatment. President Trump sowed the seeds for this dynamic with his full-throated endorsement of the malaria drug hydroxychloroquine. Even after it turned out to be a dud, Trump, Fox News, some right-wing physicians, and other right-wing media outlets continued to tout its supposed benefits. As it happened, a raft of studies, including preliminary results from the first large trial, ultimately found that ivermectin was not terribly effective at treating COVID-19. Accordingly, Boulware has since moved on to studying other drugs (including a promising antidepressant called fluvoxamine, which I’ll come back to later). Yet despite the evidence against ivermectin, the same conservative pundits who promoted hydroxychloroquine have now taken up the ivermectin cause, and, with scant scientific evidence, tout both ivermectin and hydroxychloroquine as highly effective treatments.
Naturally, this has become embedded into politics. Last spring, a bill introduced in the Colorado General Assembly led by Rep. Stephanie Luck (R-Colo.) proposed legislation that would preemptively protect doctors who prescribe off-label medications, including ivermectin and hydroxychloroquine, from disciplinary actions for deviating from the standard of care. In June, Sen. Ron Johnson (R-Wisc.) was suspended from YouTube after he posted a video praising hydroxychloroquine and ivermectin. The right-wing physicians’ group America’s Frontline Doctors charges patients $90 to be connected with providers willing to prescribe hydroxychloroquine and ivermectin. The group also regularly repeats falsehoods about vaccines; a recent article quoted a doctor saying, “Vaccinated people should be put in quarantine, and should be isolated from the society.” The researchers I spoke with all warned that the conservative zeal for these treatments could have dangerous consequences—their followers might believe so strongly in miracle drugs that they decide not to get vaccinated. Should they become infected, they might take matters into their own hands, attempt to treat themselves with the drugs, and accidentally overdose. So widespread were recent reports of people poisoning themselves with ivermectin that they bought from livestock stores, the FDA issued a warning on Saturday, tweeting, “You are not a horse. You are not a cow. Seriously, y’all. Stop it.”
Yet researchers also criticized what they see as a knee-jerk reaction by some on the left against COVID treatments. To be sure, progressives’ skepticism of treatments isn’t nearly as pronounced as conservatives’ bias against vaccines, but earlier this summer, when a major study favoring ivermectin was retracted, some left-leaning pundits gloated. And there is one key piece of nuance that has been lost in outlets’ breathless reporting about treatments that don’t seem to work. In some cases, it may be appropriate for a doctor to prescribe a COVID drug for which the evidence is mixed or not robust—say, if a patient is suffering from a condition that disqualifies them from receiving standard treatment. When prescribing drugs, physicians generally follow guidelines from the National Institutes of Health, which are based on an extensive body of studies and clinical trials. But these guidelines aren’t law. Also, because they look at overall evidence of benefit to a population rather than focusing on individual patients, there are legitimate reasons to deviate from them. If doctors think certain drugs might help a patient for specific reasons, they are allowed to—and regularly do—prescribe drugs “off-label,” or for a purpose that’s different from their approved use. Currently, the NIH recommends only a few COVID-19 drugs for outpatients at risk of severe complications—certain kinds of monoclonal antibodies, as well as some steroids.
The researchers I spoke with all endorsed the idea that physicians should have some latitude to prescribe drugs outside of these recommendations for COVID on a case-by-case basis. “In a pandemic, you don’t really have time to do huge trials,” Reiersen said. “If you want to try to do something that works, then you might have to go with lower-quality evidence, as long as it’s a relatively safe drug.”
What’s more, over the last few months, it has become clear that while vaccines are our best weapon against the pandemic, they are only one tool in the face of stressed hospitals and ICU units at capacity. Treatments could help people who have health conditions that disqualify them from being vaccinated, or that prevent the vaccine from working well. They could also help children who are too young to be eligible for the vaccine, as well as people with nasty breakthrough infections.
And how about the people who simply refuse to get vaccinated? It’s tempting to dismiss them: Don’t want a vaccine? Great! Enjoy COVID! But in public health, there’s a principle called “harm reduction,” where you help people by making a dangerous activity safer, leaving your own biases and judgments out of it. (Perhaps the most famous example of this is needle exchange centers, which aim to prevent the spread of diseases, such as HIV and hepatitis, transmitted by shared needles.) “We should do what is best for people who are sick, or to prevent people from getting sick,” Reiersen said. “I just don’t understand why these things turn into polarized political issues. It’s ridiculous.”
Once politics is out of the equation, finding an effective treatment for COVID-19 shouldn’t be hard. Many drugs commonly used for other conditions have shown promise in reducing the severity of the disease. The problem is that proving they work is incredibly expensive—a single trial can cost tens of millions of dollars. Pharmaceutical companies have that kind of money, but since generic drugs are so cheap and plentiful already, there’s no financial incentive to run such trials. So, researchers must either rely on limited and fiercely competitive government funding or philanthropy, which can get back to—guess what—politics.
Case in point: Last year, a Silicon Valley entrepreneur, Steve Kirsch, founded the COVID-19 Early Treatment Fund to subsidize studies of promising repurposed drugs. Over the course of several months, Kirsch says he spent more than $6 million of his own money supporting these trials. But somewhere along the way, Kirsch became frustrated with the government’s unwillingness to recommend treatments on the basis of small trials with encouraging results. In a recent Zoom call with me, Kirsch railed against what he saw as a “corrupt” drug approval system. “These guys were twiddling their thumbs and focused on the vaccines and not funding or paying attention to any of these trials,” he said. In the last few months, he has tweeted critically about COVID-19 vaccines and masks, suggesting that the vaccines have killed more than 25,000 people. (They have not.) He promoted tweets by the California chapter of the anti-vaccine group Children’s Health Defense. Some researchers, who requested to remain anonymous, told me that even though Kirsch supported their work early on, recently they have sought to distance themselves from him.
Politics is also exacerbating a greater barrier to finding COVID treatments, namely that it’s hard to track down enough people to enroll in drug trials. At first, this problem seemed counterintuitive to me: In the midst of a raging pandemic, surely COVID patients would want to try out drugs that could help them. Yet that’s not always true, said Jeffrey Klausner, an epidemiologist and infectious disease scientist at the University of Southern California. Privacy rules make it difficult to enroll patients through testing sites. A COVID-19 diagnosis can be overwhelming, and enrolling in a trial is an extra hurdle for patients already feeling sick. The politicization of COVID treatments may make some potential participants wary of trying a drug they’ve never heard of. Indeed, at the beginning of the pandemic, Boulware’s team struggled to launch a trial to see whether hydroxychloroquine had any benefit at all. Hardly anyone signed up. “Half the population believed that hydroxychloroquine totally worked and that therefore it was unethical to be doing a clinical trial,” he said. “And the other half believe that it totally didn’t work.” Researchers worry that the recent reports of ivermectin self-dosing could scare people off of enrolling in any kind of treatment trials in the future.
Klausner finds all of this frustrating because he’s seen what can happen when trials to see what new benefits generic drugs might offer go right. During the HIV/AIDS epidemic, gay communities mobilized to spread the word about trials. “The community, through Act Up and other organizations, really was engaged,” Klausner said. “They were pushing community members to join studies.” Those trials paved the way for the generic medication that eventually became the basis for highly effective drug cocktails that made it possible for people who were infected to live long lives.
Most of the researchers I talked with believed that COVID-19 medications will have a similar trajectory. When we finally do find a treatment, it likely won’t be a single miracle drug but a combination of a few generic drugs, refined over the course of many trials. There is good news on this front. Earlier this month, researchers cleared a major hurdle in COVID treatment research by using an antidepressant called fluvoxamine: A large, randomized controlled trial showed that the drug reduced hospitalization rates by 30 percent. A mix of that drug plus one or two others may yield even better results. Figuring that out—through studies, small trials, and larger ones—will be a massive effort. One that will be a lot easier if politics don’t get in the way.
This piece has been updated.