Safety and Efficacy of Hydroxychloroquine in COVID-19: A Systematic Review and Meta-Analysis

Ullah, Waqas; M. Abdullah, Hafez; Roomi, Sohaib; Sattar, Yasar; Almas, Talal; Narayana Gowda, Smitha; Saeed, Rehan; Mukhtar, Maryam; Ahmad, Ammar; Oliver, Tony; Alraies, M. Chadi; Haas, Donald C.; Fischman, David L.

BACKGROUND: During the initial phases of the coronavirus disease 2019 (COVID-19) epidemic, there was an unfounded fervor surrounding the use of hydroxychloroquine (HCQ); however, recently, the Centers for Disease Control and Prevention (CDC) has recommended against routine use of HCQ outside of study protocols citing possible adverse outcomes. METHODS: Multiple databases were searched to identify articles on COVID-19. An unadjusted odds ratio (OR) was used to calculate the safety and efficacy of HCQ on a random effect model. RESULTS: Twelve studies comprising 3,912 patients (HCQ 2,512 and control 1400) were included. The odds of all-cause mortality (OR: 2.23, 95% confidence interval (CI): 1.58 - 3.13, P value < 0.00001) were significantly higher in patients on HCQ compared to patients on control agent. The response to therapy assessed by negative repeat polymerase chain reaction (PCR) (OR: 1.83, 95% CI: 0.50 - 6.75, P = 0.36), radiological resolution (OR: 1.98, 95% CI: 0.47 - 8.36, P value = 0.36) and the need for invasive mechanical ventilation (IMV) (OR: 1.21, 95% CI: 0.34 - 4.33, P value = 0.76) were identical between the two groups. Overall, four times higher odds of net adverse events (NAEs) were observed in the HCQ group (OR: 4.59, 95% CI 1.73 - 12.20, P value = 0.02). The measures for individual safety endpoints were also numerically lower in the control arm; however, none of these values reached the level of statistical significance. CONCLUSIONS: HCQ might offer no benefits in terms of decreasing the viral load and radiological improvement in patients with COVID-19. HCQ appears to be associated with higher odds of all-cause mortality and NAEs.