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

Abstract

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.

COVID-19-neutralizing antibodies predict disease severity and survival

“…Remdesivir, a nucleotide analog active against SARS-CoV-2, has shown modest benefit in severe COVID-19 cases by improving time to recovery ( Beigel et al., 2020 ; Wang et al., 2020b ). Hydroxychloroquine was initially tested in patients based on in vitro studies ( Chen et al., 2020c ; Wang et al., 2020b ), but subsequent meta-analyses and randomized controlled trials have demonstrated no benefit in preventing or treating COVID-19 ( Boulware et al., 2020 ; Tang et al., 2020 ; Ullah et al., 2020 ). Morbidity and mortality due to COVID-19 is largely a consequence of adult respiratory distress syndrome (ARDS) caused by a combination of both hyperinflammatory and hypercoagulable states ( Domingo et al., 2020 ), and thus suppression of these will be key to improving outcomes, as evidenced by use of corticosteroids and current trials employing tocilizumab, an anti-IL-6 receptor antibody used to treat cytokine release syndrome ( Guaraldi et al., 2020 ).…”

COVID-19 neutralizing antibodies predict disease severity and survival

“…Hydroxychloroquine was initially tested in patients based on in vitro studies (Wang et al ., 2020; Z. Chen et al ., 2020), but subsequent meta-analyses and randomized controlled trials have demonstrated no benefit in preventing or treating COVID-19 (Boulware et al ., 2020; Tang et al ., 2020; Ullah et al ., 2020). Morbidity and mortality due to COVID-19 is largely a consequence of adult respiratory distress syndrome (ARDS) caused by a combination of both hyperinflammatory and hypercoagulable states (Domingo et al ., 2020).…”

Effect of Hydroxychloroquine on Clinical Improvement and Mortality Among Patients with COVID-19 Admitted to Four General Hospitals in Saudi Arabia

“…However, the results of these studies were conflicting as regards the ability of hydroxychloroquine to limit the radiologic progression [17][18][19]. Variability may be related to the difference in disease severity and time of re-assessment of chest imaging in different study designs.…”