Response to: “Risks of hydroxychloroquine use for COVID-19 prophylaxis”

To the Editor: Thank you to Sachdeva et al¹ for their interest in our letter, “Does hydroxychloroquine combat COVID-19? A timeline of evidence.”² As they noted, we reviewed the current literature supporting the preliminary evidence regarding the efficacy and safety of hydroxychloroquine (HCQ) as a treatment or prophylaxis for COVID-19. What we tried to emphasize is that many of these pilot studies, in our opinion, have been done under duress during a pandemic and are flawed. There is a vital need for additional high-quality prospective, randomized, placebo-controlled clinical studies to establish efficacy, safety, and guidelines for the use of HCQ to combat this virus before mainstreaming this therapy.³

The oft quoted French studies^{4 , 5} have been touted by the media and have obviously impressed several leaders of governments because these studies suggested that HCQ, a relatively cheap and heretofore readily available medication, could reduce the viral load in patients with COVID-19 and was noted to be especially efficacious if combined with azithromycin. However, the first study⁴ was small, with only 20 patients, lacked randomization, and had a short observation period. The second study⁵ lacked a control arm.

A recent Chinese trial involving 62 patients⁶ showed that HCQ treatment was associated with a shorter time to clinical recovery, manifested by a reduction in temperature and cough, than placebo. However, the participants in this study had mild disease. Therefore, it is not possible to extrapolate these results to those who are critically ill from COVID-19. Questions to be answered include but are not limited to:

• 1.Does the severity of the illness or amount of viral load impact whether the HCQ can be effectual?
• 2.Will HCQ be proven helpful in a larger prospective double-blinded and randomized study?
• 3.What dosage and schedule are the most appropriate in view of the potential for cardiac toxicity?
• 4.What are the guidelines for when this treatment should be initiated?

HCQ has been demonstrated to be antiviral but is also known for its successful anti-inflammatory actions that has resulted in it being used extensively in autoimmune diseases; it can significantly decrease the production of cytokines and, in particular, proinflammatory factors.⁷ Although the rheumatologic literature has demonstrated that HCQ is less toxic than chloroquine and a very safe medication, prolonged use and overdosing can still cause problems for our patients. Major concerns surround the potential for ventricular arrhythmias, QT prolongation, and other cardiac toxicities.

I applaud those at the front line trying desperately to help those suffering with this virus. A recent Wall Street Journal article reported data compiled from the Global Rheumatology Alliance (a coalition of rheumatologists); they reported that more than 5 dozen “people taking hydroxychloroquine and other treatments for chronic rheumatologic diseases have become infected with COVID-19, according to an analysis of emerging data that is a sign the drugs may not protect people from the new coronavirus.”⁸ These findings cast doubt on the effectiveness of HCQ prophylaxis.