COVID-19 research briefs: Corticosteroids reduce mortality in patients on oxygen; postexposure hydroxychloroquine ineffective

Reference

Boulware DR, Pullen MF, Bangdiwala AS, et al. A randomized trial of hydroxychloroquine as postexposure prophylaxis for Covid-19. N Engl J Med. Published online June 3, 2020. doi: 10.1056/NEJMoa2016638

Synopsis

Research Brief #36: The RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial randomized 11,320 hospitalized patients with suspected or confirmed COVID-19 into 1 of 6 open-label arms: azithromycin, lopinavir-ritonavir, tocilizumab, convalescent plasma, low-dose dexamethasone (6 mg once daily for 10 days), or usual care. This study, from researchers at Oxford University, reports the results from the comparison of low-dose dexamethasone (n = 2104) with usual care (n = 4321). The primary outcome was 28-day mortality. The mean age of participants was 66 years, 36% were women, and 56% had at least one major comorbidity. The groups were balanced at baseline. At the time the manuscript was written, 82% of patients had a positive test result for COVID-19, 9% had a test result pending, and 9% apparently had a negative result. Follow-up was fairly complete (95%) and there were few crossovers (7% in the usual care group received dexamethasone). The use of remdesivir was rare. Mortality was significantly reduced overall (21.6% vs 24.6%; P < .001; number needed to treat [NNT] = 33). The degree of benefit was strongly associated with the severity of illness. The benefit was greatest for the patients who required mechanical ventilation (29.0% vs 40.7%; P < .001; NNT = 9); patients who required oxygen but not mechanical ventilation benefitted somewhat less (21.5% vs 25.0%; P = .002; NNT = 29). No benefit (and, in fact, a trend toward harm) was observed for hospitalized patients who did not require either oxygen or mechanical ventilation (17.0% vs 13.2%; P = NS). The latter finding has important implications for the care of outpatients who do not receive oxygen: They should not be given a glucocorticoid in the absence of another compelling indication.

Reference: Horby P, Lim WS, Emberson J, for the RECOVERY Collaborative Group. Effect of dexamethasone in hospitalized patients with COVID-19 — preliminary report. medRxiv preprint published online June 22, 2020. doi.org/10.1101/2020.06.22.20137273.

Research Brief #37: This study is different from all other hydroxychloroquine (HCQ) studies in that it studied postexposure prophylaxis in healthy patients. The authors identified patients who had either a high-risk exposure to someone with confirmed COVID-19 — defined as exposure of at least 10 minutes, from less than 6 feet away, and without facial covering — or a moderate-risk exposure, which included a face mask but no eye shield. The authors randomized 821 initially asymptomatic persons within 4 days of exposure to receive hydroxychloroquine (800 mg once, then 600 mg in 6 to 8 hours, and then 600 mg once daily for 4 days) or matching placebo. The primary outcome was laboratory confirmed or clinically suspected COVID-19 (testing was not yet widely available) in the 14 days after enrollment. Healthcare workers accounted for two-thirds of the patients; the median age of all patients was 40 years. There was no difference between groups in the primary outcome: 49/414 (11.8%) in the HCQ group reported infection versus 58/407 (14.3%) in the placebo group (risk difference -2.4%; 95% CI -7.0 to 2.2). The findings were the same at 5, 10, and 14 days.

Reference: Boulware DR, Pullen MF, Bangdiwala AS, et al. A randomized trial of hydroxychloroquine as postexposure prophylaxis for Covid-19. N Engl J Med. Published online June 3, 2020. doi: 10.1056/NEJMoa2016638.