RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis

Abstract

Background Hydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit. Although generally safe when used for approved indications such as autoimmune disease or malaria, the safety and benefit of these treatment regimens are poorly evaluated in COVID-19. MethodsWe did a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. We included patients hospitalised between Dec 20, 2019, and April 14, 2020, with a positive laboratory finding for SARS-CoV-2. Patients who received one of the treatments of interest within 48 h of diagnosis were included in one of four treatment groups (chloroquine alone, chloroquine with a macrolide, hydroxychloroquine alone, or hydroxychloroquine with a macrolide), and patients who received none of these treatments formed the control group. Patients for whom one of the treatments of interest was initiated more than 48 h after diagnosis or while they were on mechanical ventilation, as well as patients who received remdesivir, were excluded. The main outcomes of interest were in-hospital mortality and the occurrence of de-novo ventricular arrhythmias (non-sustained or sustained ventricular tachycardia or ventricular fibrillation). Findings 96 032 patients (mean age 53•8 years, 46•3% women) with COVID-19 were hospitalised during the study period and met the inclusion criteria. Of these, 14 888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81 144 patients were in the control group. 10 698 (11•1%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9•3%), hydroxychloroquine (18•0%; hazard ratio 1

COVID-19 Therapeutics Outcome: Systematic Review and Data Analysis

“…Another study could not con rm the bene ts of chloroquineand hydroxychloroquine for COVID-19 patients even if othermedications were added, such as macrolides (81). However,healthcare providers noticed lower hospital stays and an increasedfrequency of ventricular arrhythmias when the drugs wereadministered to COVID-19 patients (81).…”

“…However, despite the study lacking acontrol group and randomization, it reported thathydroxychloroquine decreased viral loads in treating subjects (24).The effects of hydroxychloroquine were considerably more potentwhen administered with azithromycin according to clinical necessity (49). Another study could not con rm the bene ts of chloroquineand hydroxychloroquine for COVID-19 patients even if othermedications were added, such as macrolides (81). However,healthcare providers noticed lower hospital stays and an increasedfrequency of ventricular arrhythmias when the drugs wereadministered to COVID-19 patients (81).…”

Perspectives on the Early Quality of Evidence Guiding the Therapeutic Management of SARS CoV-2: A Systematic Literature Review

“…A case in point is the issue with the real-world evidence on the e cacy of hydroxychloroquine [52]. This was a multi-national registry-based study which was one of the earliest evidences in support of hydroxychloroquine for the treatment of SARS-CoV-2.…”

Enantiomers of Chloroquine and Hydroxychloroquine Exhibit Different Activities Against SARS-CoV-2 in vitro, Evidencing S-Hydroxychloroquine as a Potentially Superior Drug for COVID-19

“…These include some medications commonly used for decades, such as chloroquine, [11][12][13] arbidol, 14 ribavirin, [15][16][17] lopinavir, etc., [18][19][20] The list also contains some drugs in development, for instance, remdesivir, 11,17 a previously studied drug candidate for treating Ebola infection. [21][22] Among the most notable and also controversial repurposed drugs are chloroquine (CQ) and hydroxychloroquine (HCQ) as shown in Figure 1A, with several initial promising results especially when combined with azithromycin or zinc supplement being reported, [23][24][25][26][27][28][29][30][31] only to be followed by contradicting reports [32][33][34][35][36][37] on lack of efficacy and presence of severe side effects, especially among the higher dosed patients. Based on the preclinical results, both CQ and HCQ have displayed inhibition of viral replication.…”