Hydroxychloroquine and COVID-19 story: is the low-dose treatment the missing link? A comprehensive review and meta-analysis.

Hydroxychloroquine (HCQ) has been repurposed and used for the treatment of COVID-19 patients; however, its efficacy remains controversial, maybe partly due to the dosage, ranging from 200 to 800 mg/day, reported in different studies. Indeed, HCQ low dose (≤ 2.4 g/5 days) showed a lower risk of side effects compared to high doses. In this study, we performed a systematic review and meta-analysis to investigate the effect of low-dose HCQ used alone on three outcomes including in-hospital mortality, the need for mechanical ventilation, and ICU admission in COVID-19 patients. A systematic review of English literature was conducted from January 2020 to April 2022, in PubMed, Cochrane Library, and Google Scholar. Studies reporting a dosage of 400 mg twice the first day, followed by 200 mg twice for four days were included. Pooled odds ratios and 95% confidence intervals were calculated using random-effects models. Eleven studies (12,503 patients) were retained in the quantitative analysis, four observational cohort studies, and seven RCTs. When pooling both observational and RCTs, low-dose HCQ was associated with decreased mortality (OR = 0.73, 95% CI: [0.55-0.97], I = 58%), but not with mechanical ventilation need (OR = 1.03, 95% CI: [0.56-1.89], I = 67%) and ICU admission rate (OR = 0.70, 95% CI: [0.42-1.17], I = 47%). However, no effect was observed when pooling only RCTs. Despite RCTs limitations, treatment with low-dose HCQ was not associated with improvement in mortality, mechanical ventilation need and ICU admission rate in COVID-19 patients.