The efficacy and safety of hydroxychloroquine for COVID-19 prophylaxis: A systematic review and meta-analysis of randomized trials

Abstract

Background Populations such as healthcare workers (HCW) that are unable to practice physical distancing are at high risk of acquiring Coronavirus disease-2019 (COVID-19). In these cases pharmacological prophylaxis would be a solution to reduce severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) transmission. Hydroxychloroquine has in vitro antiviral properties against SARS CoV-2. We therefore sought to determine the efficacy and safety of hydroxychloroquine as prophylaxis for COVID-19. Methods and findings We electronically searched EMBASE, MEDLINE, the Cochrane COVID-19 Register of Controlled Trials, Epistemonikos COVID-19, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform up to September 28th, 2020 for randomized controlled trials (RCTs). We calculated pooled relative risks (RRs) for dichotomous outcomes with the corresponding 95% confidence intervals (CIs) using a random-effect model. We identified four RCTs (n = 4921) that met our eligibility criteria. The use of hydroxychloroquine, compared to placebo, did not reduce the risks of developing COVID-19 (RR 0.82, 95% CI 0.65 to 1.04, moderate certainty), hospitalization (RR 0.72, 95% CI 0.34 to 1.50, moderate certainty), or mortality (RR 3.26, 95% CI 0.13 to 79.74, low certainty), however, hydroxychloroquine use increased the risk of adverse events (RR 2.76, 95% CI 1.38 to 5.55, moderate certainty). Conclusion Although pharmacologic prophylaxis is an attractive preventive strategy against COVID-19, the current body of evidence failed to show clinical benefit for prophylactic hydroxychloroquine and showed a higher risk of adverse events when compared to placebo or no prophylaxis.

Hydroxychloroquine For Prophylaxis Of COVID-19 In Health Workers: A Randomized Clinical Trial

“…Our trial is one of the several trials that have evaluated the efficacy and security of HCQ. Other trials with the same drug and population have found a lower number of infections in the HCQ groups, but without statistical significance in the analysis [20][21][22] . The doses and day of application vary considerably in the different essays, in general lower or for shorter time than ours, may have had an impact in the results and that some doses or days of therapy are insufficient to prevent infections.…”

Prophylaxis for covid-19: living systematic review and network meta-analysis

“…These findings are consistent with those reported in a meta-analysis of hydroxychloroquine prophylaxis against no prophylaxis, which did not find any statistical evidence of a benefit with hydroxychloroquine prophylaxis for the patient-important outcomes of SARS-CoV-2 infection, hospital admission and death. 38 The study also concluded that hydroxychloroquine is likely to increase the risk of adverse effects. 38 The risk of death is much lower in people at risk of covid-19 compared to those diagnosed with covid-19.…”

“…38 The study also concluded that hydroxychloroquine is likely to increase the risk of adverse effects. 38 The risk of death is much lower in people at risk of covid-19 compared to those diagnosed with covid-19. 7 Similarly, the risk of SARS-CoV-2 infection varies depending on pre-or post-exposure status and setting.…”

Prophylaxis against covid-19: living systematic review and network meta-analysis

“…These findings are consistent with those reported in a meta-analysis of hydroxychloroquine prophylaxis compared with no prophylaxis, which did not find any statistical evidence of a benefit with hydroxychloroquine prophylaxis for the patient important outcomes of SARS-CoV-2 infection, hospital admission, and mortality. 39 The study concluded that hydroxychloroquine is likely to increase the risk of adverse effects. 39 Furthermore, the data are consistent with three meta-analyses [40][41][42] and one network metaanalysis 8 evaluating ivermectin as treatment for covid-19.…”

“…39 The study concluded that hydroxychloroquine is likely to increase the risk of adverse effects. 39 Furthermore, the data are consistent with three meta-analyses [40][41][42] and one network metaanalysis 8 evaluating ivermectin as treatment for covid-19. In contrast with other meta-analyses, we rated the certainty as very low because of serious risk of bias and very serious imprecision.…”