Effectiveness and Safety of Chloroquine or Hydroxychloroquine as a mono-therapy or in combination with Azithromycin in the treatment of COVID-19 patients: Systematic Review and Meta-Analysis

Ghazy, R. M.; Almaghraby, A.; Shaaban, R.; Kamal, A.; Beshir, H.; Moursi, A.; Taha, S. H. N.; Ramadan, A.

Many recent studies have investigated the role of either Chloroquine (CQ) alone, Hydroxychloroquine (HCQ) alone, or CQ/HCQ in combination with azithromycin (AZM) in management of the emerging coronavirus. This systematic review and meta-analysis of either published or preprint observational or interventional studies were conducted to assess the cure rate, duration of hospital stay, radiological progression, clinical worsening, need for mechanical ventilation, the occurrence of side effects, and mortality. A search of the online database through June 2020 was performed and examined the reference lists of pertinent articles for in-vivo studies only. Pooled relative risks (RRs), standard mean, of 95 % confidence intervals (CIs) were calculated with the random-effects model. Results: The duration of hospital stay was shorter in the standard care in comparison with HCQ group, the standard mean of hospital stay was 0.57, 95% CI, and 0.20-0.94. Overall virological cure, or more specifically at day 4, 10, and 14 among patients exposed to HCQ did not differ significantly from the standard care [(RR=0.92, 95% CI 0.78-1.15), (RR=1.11, 95% CI 0.74-1.65), (RR=1.21, 95%CI 0.70-2.01), and (RR=0.98, 95% CI, 0.76-1.27)] respectively. Radiological improvement or clinical worsening was not statistically different between HCQ and standard care [(RR=1.11, 95% CI 0.64-1.65) and (RR=1.28, 95% CI 0.33-4.99)]. The need for mechanical ventilation (MV) was not significant between the HCQ group and the standard care (RR= 1.5, 95%CI 0.78-2.89). Side effects were more reported in the HCQ group than the standard care (RR=3.14, 95% CI 1.58- 6.24). Mortality among HCQ was not affected by receiving HCQ (RR=3.14, 95% CI 1.58-6.24), meta-regression analysis revealed that country is a strong predictor of mortality. The duration of hospital stay among the HCQ and AZM didn not differ significantly from the standard care (standard mean= 0.77, 95% CI 0.46-1.08). Despite virological cure and need for MV did not differ significantly [(RR= 3.23, 95% CI 0.70-14.97) and (RR=1.27, 95%CI 0.7-2.13)] respectively. Mortality among the HCQ+AZM was more significantly higher than among the standard care (RR= 1.8, 95% CI 1.19-2.27). Conclusion: Despite the scarcity of published data of good quality, the effectiveness and safety of either HCQ alone or in combination with AZM in treating the pandemic of COVID-19 cannot be assured. Future randomized control trials need to be carried out to verify this conclusion.