Latest recommendations reject hydroxychloroquine, support remdesivir

ACP has retired its living practice points on the use of chloroquine or hydroxychloroquine alone or in combination with azithromycin for COVID-19, concluding that there is still insufficient evidence to support the efficacy or safety of these therapies. The practice points currently say that the drugs should not be used for prophylaxis or treatment of COVID-19, although they note that clinicians may choose to treat hospitalized COVID-19-positive patients with chloroquine or hydroxychloroquine alone or in combination with azithromycin in the context of a clinical trial, using shared and informed decision making with patients (and their families). The College's Scientific Medical Policy Committee reviewed the evidence released since the practice points were initially published in May and found that several trials had been halted and recently completed studies had high risk of bias and conflicting direction and magnitude of results, according to the update published by Annals of Internal Medicine on July 30.

The BMJ also published a rapid recommendation on COVID-19 treatment on July 30. Its new clinical practice guideline from an international group of experts makes a weak recommendation for the use of remdesivir in severe COVID-19 (defined as respiratory rate >30 breaths/min, respiratory distress, or oxygen saturation <94% on room air). A second recommendation supports continuation of randomized controlled trials of remdesivir. The recommendations were based on a systematic review, also published by The BMJ on July 30, which found low-certainty evidence that remdesivir may be effective in reducing time to clinical improvement and may decrease mortality in patients with severe COVID-19, but probably has no important effects on need for mechanical ventilation or hospital length of stay.

That review covered other drug treatments for COVID-19 as well. It found that glucocorticoids were the only intervention with evidence for a reduction in death compared with standard care (risk difference, 37 fewer per 1,000 patients; moderate certainty) and mechanical ventilation (risk difference, 31 fewer per 1,000 patients; moderate certainty). Three drugs were found to possibly reduce symptom duration: hydroxychloroquine (mean difference, −4.5 days; low certainty), remdesivir (mean difference, −2.6 days; moderate certainty), and lopinavir-ritonavir (mean difference, −1.2 days; low certainty). The review noted that hydroxychloroquine might increase the risk of adverse events compared with the other interventions, and remdesivir probably does not. However, the authors pointed out that their analysis of 23 randomized controlled trials found very low certainty of the evidence for most comparisons because of risk of bias and serious imprecision.

A cautionary note about the use of steroids for COVID-19 was offered by a JAMA Viewpoint published July 30. Strongyloides hyperinfection is a potentially severe, but preventable, complication of steroid therapy. The article explains that a majority of individuals with strongyloidiasis are asymptomatic, and the most common precipitator of hyperinfection is a corticosteroid. The parasite is prevalent in tropical and subtropical populations, including immigrants from those regions. “With more than 44 million first-generation immigrants residing in the US, many of whom work essential jobs and live in environments less conducive to social distancing, the convergence of risk for both chronic strongyloidiasis and COVID-19 infection could be common and is concerning,” the article said. The authors said that ivermectin could be used as a preventive strategy for at-risk patients, and they offer recommendations on testing and treatment of Strongyloides based on patients' infection risk and care setting.

Finally, a new industry-funded study compared outcomes from severe COVID-19 in patients treated in a remdesivir trial and a cohort who received standard care. At day 14, 74.4% of the 312 patients in the remdesivir cohort had recovered versus 59.0% of the 818 receiving standard care (adjusted odds ratio [OR], 2.03; 95% CI, 1.34 to 3.08; P<0.001). Mortality at 14 days was 7.6% versus 12.5% (adjusted OR, 0.38; 95% CI, 0.22 to 0.68; P=0.001). The study authors said that the results were “highly encouraging” and concordant with previously published preliminary data. “Ongoing studies and real-world data will further determine the optimal role of remdesivir for the treatment of COVID-19,” they wrote.