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.

Efficacy and Safety of Anti-malarial Drugs (Chloroquine and Hydroxy-Chloroquine) in Treatment of COVID-19 Infection: A Systematic Review and Meta-Analysis.

Background: Anti-malarial drugs inhibit coronaviruses in-vitro. Few published studies have evaluated the safety and efficacy of these drugs in the treatment of COVID-19 infection. Materials and Methods: This is a systematic review and meta-analysis of clinical trials and observational studies. Major database searches were carried out up until June 5, 2020. Participants admitted with RT-PCR-confirmed SARS Cov-2 (COVID-19) infection were included. The "Intervention group" received anti-malarial drugs with or without other drugs (Azithromycin) administered as an adjunct to the standard treatment/care. The "Control group" received treatment except anti-malarial drugs. The primary outcome is "all-cause mortality." Secondary outcome measures were effects on clinical and laboratory parameters and adverse events. Results: Of 3,472 citations, 17 (six clinical trials and 11 observational studies) studies provided data of 8,071 participants. Compared to the control, Hydroxy-chloroquine (HCQ) has no significant effect on mortality [(OR 0.87; 95% CI 0.46-1.64); eight observational studies; N = 5,944]. Data from a single, small non-randomized trial (N = 42) also reached a similar conclusion (OR 1.94; 95% CI 0.07-50.57; p = 0.69). Compared to the control, HCQ plus Azithromycin (AZM) significantly increased mortality [(OR 2.84; 95% CI 2.19-3.69); four observational studies; N = 2,310]. Compared to the control, risk of any adverse event was significantly increased in HCQ group [(OR 3.35; 95% CI 1.58-7.13); four clinical trials; N = 263]. Compared to control, risk of adverse cardiac events (abnormal ECG, arrhythmia, or QT prolongation) were not significantly increased in HCQ group (but significantly increased in the HCQ plus AZM group). The GRADE evidence generated for all the outcomes was of "very low-quality." Conclusions: As very low quality evidence suggests an increased risk of mortality and adverse event with HCQ plus Azithromycin combination (not HCQ alone), caution should be exercised while prescribing this combination for treatment of hospitalized adults with COVID-19 infection. Good quality, multi-centric RCTs (including both hospitalized and non-hospitalized patients) are required for any firm recommendation to be made during the ongoing pandemic. OSF Protocol Registration Link: https://osf.io/6zxsu.