Hydroxychloroquine/Chloroquine in COVID-19 With Focus on Hospitalized Patients – A Systematic Review

Background

In the beginning of the COVID-19 pandemic, many hospitalized patients received empiric hydroxychloroquine/chloroquine (HC/CQ). Although some retrospective-observational trials suggested potential benefit, all subsequent randomized clinical trials (RCTs) failed to show benefit and use generally ceased. Herein, we summarize key studies that clinicians advising patients on HC/CQ’s efficacy:safety calculus in hospitalized COVID-19 patients would want to know about in a practical one-stop-shopping source.

Methods

Pubmed and Google were searched on November 4, 2021. Search words included: COVID-19, hydroxychloroquine, chloroquine, in vitro , animal studies, clinical trials, and meta-analyses. Studies were assessed for import and included if considered impactful for benefit:risk assessment.

Results

These searches led to inclusion of 12 in vitro and animal reports; 12 retrospective-observational trials, 19 interventional clinical trials (17 RCTs, 1 single-arm, 1 controlled but unblinded), and 51 meta-analyses in hospitalized patients.

Inconsistent efficacy was seen in vitro and in animal studies for coronaviruses and nil in SARS-CoV-2 animal models specifically. Most retrospective-observational studies in hospitalized COVID-19 patients found no efficacy; QT prolongation and increased adverse events and mortality were reported in some. All RCTs and almost all meta-analyses provided robust data showing no benefit in overall populations and subgroups, yet concerning safety issues in many.

Conclusions

HC/CQ have inconsistent anti-coronavirus efficacy in vitro and in animal models, and no convincing efficacy yet substantial safety issues in the overwhelming majority of retrospective-observational trials, RCTs, and meta-analyses in hospitalized COVID-19 patients. HC/CQ should not be prescribed for hospitalized COVID-19 patients outside of clinical trials.

Key Summary Points

Preclinical hydroxychloroquine/chloroquine in vitro studies found inconsistent activity against coronaviruses including SARS-CoV-2.

Preclinical hydroxychloroquine/chloroquine animals studies found inconsistent efficacy for coronaviruses in general and none for SARS-CoV-2.

The overhwelming majority of RCTs and retrospective-observational trials found no benefit for hydroxychloroquine/chloroquine in hospitalized COVID-19 patients, and many found concerning safety signals.

The majority of RCTs and retrospective-observational trials found no benefit for hydroxychloroquine/chloroquine in COVID-19 outpatients or for pre- or post-exposure prophylaxis, and some found concerning safety signals.

The overwhelming majority of meta-analyses found no benefit for hydroxychloroquine/chloroquine in COVID-19 inpatients, outpatients, or for prophylaxis, and many found concerning safety signals.