Researchers had been exploring the use of antimalarials like HCQ and chloroquine (CQ) against viral infections for decades, so the recommendation wasn’t totally implausible. CQ had shown promise against the 2002 outbreak of sudden acute respiratory syndrome (SARS), another coronavirus, by inhibiting viral replication.

In addition, some hypothesized that CQ or HCQ could inhibit immune response that could lead to lung and other organ damage in patients with COVID-19.

Trump’s initial endorsements came from two sources. A letter in BioScience Trends summarized the experience of a Chinese medical group, reporting that “results from more than 100 patients have demonstrated that chloroquine phosphate is superior to the control treatment in inhibiting the exacerbation of pneumonia, improving lung imaging findings, promoting a virus negative conversion, and shortening the disease course.” The letter, however, included no additional detail about study design, patient selection criteria, outcomes, or safety. Read the letter at https://apha.us/BioSciTrends.

An International Journal of Antimicrobial Agents study out of France included more detail but still had significant limitations. Read that study at https://apha.us/HCQFrance.

The French study had a very small sample size—42 patients were enrolled, of whom 16 were controls. Still, it found that patients who were positive for COVID-19 and were treated with HCQ, sometimes in combination with azithromycin depending on a patient’s clinical presentation, had a significantly reduced viral load compared with controls.

HCQ hype was born. Though evidence supporting their effectiveness was scant, FDA approved HCQ and CQ for COVID-19 treatment by EUA on March 28. EUA was granted based on SARS-CoV-2’s potential to cause life-threatening disease; a reasonable belief that HCQ/CQ could effectively treat COVID-19 based on the limited in vitro and anecdotal clinical data in case series, and that the drugs’ known and potential benefits outweighed their known and potential risks; and the lack of an adequate, approved, and available alternative treatment.

Literature about HCQ and COVID-19 began to proliferate, but most consisted entirely of speculation (https://apha.us/Speculation), hypothesis (https://apha.us/Hypothesis), calls for further study (https://apha.us/FurtherStudy), or trial design proposals (https://apha.us/Proposal).