ABSTRACT
BACKGROUND: Ivermectin became a popular choice for COVID-19 treatment among clinicians and the public following encouraging results from pre-print trials and in vitro studies. Early reviews recommended the use of ivermectin based largely on non-peer-reviewed evidence, which may not be robust. This systematic review and meta-analysis assessed the efficacy and safety of ivermectin for treating COVID-19 based on peer-reviewed randomized controlled trials (RCTs) and observational studies (OSs). METHODS: MEDLINE, EMBASE and PubMed were searched from 1 January 2020 to 1 September 2021 for relevant studies. Outcomes included time to viral clearance, duration of hospitalization, mortality, incidence of mechanical ventilation and incidence of adverse events. RoB2 and ROBINS-I were used to assess risk of bias. Random-effects meta-analyses were conducted. GRADE was used to evaluate quality of evidence. RESULTS: Three OSs and 14 RCTs were included in the review. Most RCTs were rated as having some concerns in regards to risk of bias, while OSs were mainly rated as having a moderate risk of bias. Based on meta-analysis of RCTs, the use of ivermectin was not associated with reduction in time to viral clearance, duration of hospitalization, incidence of mortality and incidence of mechanical ventilation. Ivermectin did not significantly increase incidence of adverse events. Meta-analysis of OSs agrees with findings from RCT studies. CONCLUSIONS: Based on very low to moderate quality of evidence, ivermectin was not efficacious at managing COVID-19. Its safety profile permits its use in trial settings to further clarify its role in COVID-19 treatment. PROTOCOL REGISTRATION: The review was prospectively registered in PROSPERO (CRD42021275302).