The Use of Chloroquine and Hydroxychloroquine for Prophylaxis and Treatment of COVID-19

Project Summary Title and Description

The Use of Chloroquine and Hydroxychloroquine for Prophylaxis and Treatment of COVID-19
The purpose of this review is to determine if hydroxychloroquine or chloroquine is effective and safe when used alone or when combined with azithromycin for the prophylaxis and treatment of COVID-19.
Authors of Report
Methodology description
On May 8, 2020, we comprehensively searched: PubMed-Medline, EMBASE-OVID, Scopus, Web of Science, the Cochrane Library, pre-prints and pre-proofs from the following web pages:,,, and Trial registry websites of the WHO, USA, and China:,, and The searches were very broad containing the agents under investigation “hydroxychloroquine or chloroquine” and the virus or disease state “SARS-CoV-2 or COVID-19”. As such, it would capture efficacy and harm outcome studies as well as active treatment and prophylaxis studies. We did not predefine outcomes to allow the broadest assessment of the literature base available. Three investigators independently selected studies, and disagreements were resolved by discussion. We used a pre-defined extraction sheet that was modified dynamically as new outcomes were identified in the studies. Extractions were performed independently by two authors and revised by two other authors. Discrepancies in extractions were resolved by discussion. Risk of bias assessments were performed independently by two investigators in comparative studies using the ROBINS-I tool for non-randomized studies of interventions and the Cochrane risk of bias 2.0 tool for randomized controlled trials. Discrepancies in risk of bias assessments were resolved by discussion. We only performed random effects meta-analyses of two RCTs for dichotomous outcomes. The inverse variance method was used, and effects were described as relative risks (RR) and their 95% confidence intervals. Heterogeneity of effects between RCTs were described with the I2 statistic, being a value >60% considered high heterogeneity. The certainty or quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach (27). GRADE profile v2 tables were developed in GRADEpro Guideline Development Tool.
Funding Source
Prepared by the University of Connecticut Evidence-based Practice Center under Contract No. HHSA290-2015-00012I | Task Order 1

Key Questions

1. Key Question 1: Is hydroxychloroquine or chloroquine effective and safe when used alone or when combined with azithromycin for the prophylaxis and treatment of COVID-19

Associated Extraction Forms

Associated Studies (each link opens a new tab)

Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial
Preliminary study of hydroxychloroquine sulfate in treating common coronavirus disease (COVID-19) patients in 20192020
Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial
Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study)
Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents 2020 (in press)2020
Clinical Outcomes of Hydroxychloroquine in Hospitalized Patients with COVID-19: A Quasi- Randomized Comparative Study2020
No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial
Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: a pilot observational study2020
No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection2020
Title Unavailable2020
The QT Interval in patients with SARS-CoV-2 infection treated with hydroxychloroquine/azithromycin2020
Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxychloroquine Alone or in Combination With Azithromycin in an Intensive Care Unit.
Experience with Hydroxychloroquine and Azithromycin in the COVID-19 Pandemic: Implications for QT Interval Monitoring
QT Interval Prolongation and Torsade De Pointes in Patients with COVID-19 treated with Hydroxychloroquine/Azithromycin
The Effect of Chloroquine, Hydroxychloroquine and Azithromycin on the Corrected QT Interval in Patients with SARS-CoV-2 Infection.2020
Chloroquine-induced QTc prolongation in COVID-19 patients2020
Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19
Hydroxychloroquine application is associated with a decreased mortality in critically ill patients with COVID-19
Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19).2020
Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease: A retrospective study
Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study.2020
Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19
Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19.2020
Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial.

Downloadable Data Content

  • XLSX Project Data