The Rise and Fall of Hydroxychloroquine for the Treatment and Prevention of COVID-19

Abstract

The efficacy and safety of hydroxychloroquine (HCQ) for the prevention and treatment of COVID-19 has received great attention, and most notably, the enthusiasm for HCQ has been one of politicization rather than science. Laboratory studies and case series published early in the pandemic supported its efficacy. The scientific community raced to conduct observational and randomized evaluations of the drug in all stages of the disease, including prophylaxis, early treatment, and advanced disease. Yet a divisive media response affected recruitment, funding, and subsequent enthusiasm for continuing scientific investigations. Of the more than 300 HCQ trials registered, fewer than 50% report having recruited any patients, and most trials might fail to achieve any useful portions of their intended sample size. Multiple observational studies and two large randomized trials have demonstrated HCQ does not offer efficacy against COVID-19 in hospitalized patients. Prophylaxis studies and early treatment studies provided heterogeneous results and are plagued by low event rates and poor study outcome monitoring. Emerging high-quality evaluations of prophylaxis and early treatment do not support a role for HCQ in these populations. The story of HCQ for COVID-19 has followed a pattern of initial enthusiasm supported by poor quality evidence, followed by disappointment based on more rigorous evaluations. The experience of HCQ in the COVID-19 era calls for the depoliticization of science away from media glare.

Figure 1.

Number of active registered trials investigating hydroxychloroquine by date among patient populations of prophylaxis, outpatient, and hospitalized settings. This figure appears in color at www.ajtmh.org.