Critical thinking about medicine or any topic requires weighing multiple sources against one another and distinguishing between degrees of certainty, not ruling out all sources of evidence but one and equating “unproven” with “false.” The approach to health information increasingly taken by public officials, reporters, and social media—under which any statement is “unproven” and must be assumed harmful, barring some definitive pronouncement by public health authorities to the contrary—is thus not only authoritarian but also damaging to public health and science as a whole.
Imperial County, California, a poor, largely Hispanic agricultural region in the southeastern corner of the state, has been hit hard by Covid-19. By the end of January, according to the New York Times’s Covid-19 database, Imperial County had suffered 845 Covid deaths, or 4.7 per thousand inhabitants—a rate almost 80 percent higher than the U.S. average. The case fatality rate in Imperial County is 1.44 percent, the second-highest in California—and was significantly higher, 2.10 percent, at the end of October 2021 before the Omicron wave.
Two doctors in Imperial County, though—George Fareed and Brian Tyson, who run the All Valley Urgent Care network of medical centers—claim to have done far better with their Covid-19 patients. In fact, they claim near-perfect success: in a book that they published last January, they claim to have seen more than 7,000 patients and had only three deaths, all among patients who began treatment in later disease stages. A statistical analysis of part of their results by the statistician Mathew Crawford, included in their book, counts only seven hospitalizations and three deaths among 4,376 patients seen up through March 13, 2021—a reduction in hospitalization risk of well over 90 percent from the county average, even after (admittedly imperfect) statistical adjustments for differences in age between Fareed and Tyson’s patients and the general population.
According to prevailing medical views, Fareed and Tyson’s claimed results should be impossible. The doctors’ first protocol was based around hydroxychloroquine (HCQ), a repurposed anti-malarial drug, with other drugs such as ivermectin as more recent additions. Received opinion on the drugs is that ivermectin is at best unproven in treating Covid-19 (the Food and Drug Administration maintains an official webpage warning against using it as a treatment for the virus), and that HCQ has been actively disproved: early optimism from laboratory experiments and small clinical studies did not hold up in larger, more rigorous trials.
Such opinions have influenced not just news coverage but also the moderation policies of social media platforms, which have imposed ever-stricter rules against “misinformation” (meaning, in practice, contradicting American public health authorities). After Fareed and Tyson spoke by invitation at a meeting of the Imperial County Board of Supervisors, the Los Angeles Times ran an article noting that the Imperial County Medical Society “had urged supervisors to ‘not contribute to the dissemination of false or misleading information by legitimizing unproven treatments.’” The paper also quoted an executive at an Imperial County hospital, saying, “We need to stick with what we know is approved by the FDA for COVID-19 treatments. . . . Misinformation itself ought to be stopped.” In December, Twitter also suspended Tyson’s account for breaking its policies against Covid misinformation.
The dismissal of hydroxychloroquine as a possible Covid-19 treatment, however, was never based on solid science. The Los Angeles Times article reveals a fundamentally authoritarian worldview: medical claims are “unproven,” and dangerous for the public to discuss, until some official body endorses them—an approach that threatens public health and science alike.
Interest in hydroxychloroquine as a coronavirus treatment stretches back at least to 2005, when an in vitro study showed that chloroquine, a very similar compound, might protect against SARS infection. Based on laboratory studies and small clinical trials, medical authorities in China and South Korea recommended chloroquine as a Covid-19 treatment in February 2020.
Some doctors outside East Asia followed. Vladimir Zelenko, a doctor in a Hasidic community in New York, advocated a combination of HCQ, azithromycin (an antibiotic to guard against secondary infections), and a zinc supplement: HCQ increases the uptake of zinc ions into cells, a property that Zelenko surmised might provide antiviral effects. In an open letter in April 2020, Zelenko claimed to have treated about 1,450 patients, including 405 that he judged “high risk,” with only two deaths. Luigi Cavanna, a doctor in Piacenza, Italy, also claimed about the same time that thanks to an HCQ treatment protocol, none of his patients had died and only 5 percent were hospitalized—one-sixth the contemporaneous Italian hospitalization rate of over 30 percent. Many more systematic “observational” studies of HCQ—comparing patients in a hospital or elsewhere who received a drug (because of their own or a doctor’s choice) with those who did not—returned good results both as a treatment of Covid-19 cases (including one large study from the Henry Ford Health System in metropolitan Detroit) and for prevention of Covid-19 in individuals at high exposure risk. One especially striking example of the latter is a set of 11 “case-control” studies from India, where medical authorities recommended but did not mandate a weekly prophylactic dose of HCQ for medical workers. Most of these studies found that workers who took HCQ had reduced odds of testing positive for SARS-CoV-2 antibodies, with especially marked reductions for those who took six or more doses of the protocol.
Medical researchers tend to discount doctors’ reports and observational studies—which, granted, have many potential biases that can’t always be spotted or corrected. For instance, observational studies can underestimate the efficacy of a treatment that’s given more often to sicker patients—or overestimate it, if health-conscious patients are more likely to demand experimental treatments, or if doctors who give ineffective experimental drugs are also more likely to give effective experimental drugs (this latter point was a common and valid criticism of the Henry Ford study). So doctors generally consider randomized trials, which avoid these classes of bias, to be more reliable—though they have drawbacks, too, such as considerably greater expense and, therefore, typically smaller sample sizes.
And most analyses of randomized trials of HCQ—on the basis of which mainstream medical opinion decided that it doesn’t work for Covid-19—do draw negative conclusions. For instance, a February 2021 review by Cochrane, an organization that produces comprehensive reviews of randomized trials, concludes, “HCQ for people infected with COVID‐19 has little or no effect on the risk of death and probably no effect on progression to mechanical ventilation.” Another meta-analysis in Nature by Cathrine Axfors et al. estimates an 11 percent increase in risk of death on the basis of 26 randomized trials.
The results of both meta-analyses were essentially determined by two large, similar trials: the Solidarity trial run by the World Health Organization and the Recovery trial at the University of Oxford. These trials accounted together for over 97 percent of the statistical weight in Cochrane’s main analysis, and both claimed to rule out more than a tiny benefit of HCQ for hospitalized Covid-19 patients.
But neither trial disproves claims such as Fareed and Tyson’s. First and most importantly, both trials were on hospitalized patients and are not necessarily applicable to “outpatients” earlier in the disease course. Antiviral treatments work better earlier: for instance, oseltamivir (also known as Tamiflu), an antiviral influenza treatment, works well if started within two days of symptom onset, but not later. In Covid-19, viral load peaks soon after symptom onset, and viral replication has already ceased in most hospitalized patients, guaranteeing that antiviral treatments will have limited effect. One review in The Lancet found that dozens of studies consistently find that viral load in Covid-19 peaks in the first week of symptoms and that “No study detected live virus beyond day 9 of illness.”