Effect of chloroquine and hydroxychloroquine on COVID-19 virological outcomes: An updated meta-analysis

As anti-malarial drugs have been found to inhibit Corona viruses in vitro, studies have evaluated the effect of these drugs inCOVID-19 infection. We conducted an updated meta-analysis of clinical trials and observational studies published till June 2020. Patients with reverse transcription polymerase chain reaction (RT-PCR) confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (COVID-19) infection were included. The drugs used in the intervention group are Chloroquine (CQ)/Hydroxychloroquine (HCQ) with or without Azithromycin. The primary outcome is time to achieve virological cure. Of 1040 citations, 11 studies provided data of 1215 patients. Compared to control, CQ/HCQ has no significant effect on the time to negative COVID-19 RT-PCR results, neither in clinical trials (mean difference [MD] 1.55; 95% confidence interval [CI] - 0.7 to 3.79; P = 0.18; n = 180), nor in observational studies (MD 1.14; 95%CI - 11.98 to 14.26; P = 0.86, n = 407). CQ/HCQ did not affect the virological cure after day 3, 7, 10, 14, 21 and 28; except after day 5, as shown by a single small non-randomised trial (odds ratio [OR] 9.33; 95% CI 1.51 to 57.65; P = 0.02, n = 30). Pooled data from 2 observational studies showed a significant effect of CQ/HCQ on virological cure by after day 10 (OR 7.86; 95% CI 4.4 to 14.04, P < 0.001, n = 373) and day 14 (OR 6.37; 95% CI 3.01 to 13.48, P < 0.001, n = 407). The GRADE evidence generated was of "very low-quality/certainty". To conclude, CQ/HCQ does not affect the time to virological cure compared to usual/standard of care in COVID-19 infection. Recurrent infection in a smaller number of patients was noted in the CQ/HCQ group. As the evidence generated was of "very low-quality/certainty)", large good quality studies are needed to confirm the present findings.