Hydroxychloroquine for the management of COVID-19: Hope or Hype? A Systematic review of the current evidence

Umesh Devappa Suranagi; Harmeet Singh Rehan; Nitesh Goyal

A study group from Wuhan University, China conducted an RCT to demonstrate the efficacy of HCQ in COVID-19 patients. 62 patients were randomized 1:1 with HCQ 400mg for 5 days including standard care as compared with standard care alone. Time taken to clinical recovery (TTCR), clinical characteristics, and radiological results were assessed at baseline and 5 days after treatment with HCQ. Researchers reported that TTCR, body temperature recovery time and cough remission time were significantly shortened in the HCQ treatment group. Besides, a larger proportion of patients with improved pneumonia were in the HCQ treatment group (80.6%) as compared with the control group (54.8%). Four patients in the control group progressed to severe illness. The researchers concluded that HCQ significantly shortens TTCR and promotes the resolution of pneumonia in COVID-19 patients. 26 A six-day pilot, uncontrolled, non-comparative observational follow-up study was conducted by French investigators to assess the Clinical and microbiological effect of a combination of HCQ and azithromycin in 80 COVID-19 patients. The investigators reported that all patients but two (an 86 yr old succumbed to illness, a 74 yr old needed ICU) showed clinical improvement with the combination therapy. qPCR testing showed a rapid fall of nasopharyngeal viral load-83% and 93% patients were negative at Day 7, and Day 8 respectively. 97.5% of respiratory samples were negative for virus cultures at Day 5. The researchers urged to evaluate the combination strategy to treat patients in early course and avoid the spread of the disease. 27 Imitating the previous non-randomized open label study by Gautret et al 23 another group of French investigators intended to evaluate the rapid antiviral clearance or clinical benefit with the Combination of HCQ and azithromycin in patients with severe COVID-19. The researchers prospectively assessed the virological clearance and clinical outcome in 11 patients. They used similar dosage regimen of HCQ (600 mg/d for 10 days) and azithromycin (500 mg Day 1 and 250 mg days 2 to 5) as used by Gautret et al 23 , they noted that in contrast to the previous findings, the current study had 8 out of 10 patients (except one death) remaining positive for SARS-CoV2 RNA at days 5 to 6 after treatment initiation, one patient died within 5 days, two were transferred to ICU, and one patient dropped out due to prolongation of QT interval. Investigators concluded that there is no evidence of a strong antiviral activity or clinical benefit of the combination of HCQ and azithromycin for the treatment of hospitalized patients with severe COVID-19. 24 In a retrospective study, group of American researchers reported increased QT interval in 84 COVID-19 patients treated with Hydroxychloroquine/azithromycin combination. The authors noted that in 30% of patients, increase in QTc was greater than 40ms and 11% patients showed QTc increase to greater than 500ms, they commented that development of acute renal failure during the therapy could be a strong predictor of extreme QTc prolongation. 44 (Table 3) Table 3 Summary of preprint articles reporting the use of HCQ in treatment of COVID-19 patients All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity.