The impact of ivermectin on COVID-19 outcomes: a systematic review and meta-analysis

Abstract

Background: The COVID-19 pandemic, resulting in approximately seven million deaths globally, underscores the urgency for effective treatments. Ivermectin, among several repurposed drugs, garnered interest due to its antiviral properties. However, conflicting evidence from observational studies and randomized controlled trials raised questions about its efficacy and safety.

Method: This systematic review and meta-analysis followed MOOSE and PRISMA guidelines. Comprehensive searches were conducted in databases including Scopus, Embase, PubMed, and Web of Science up to April 2024. Data were extracted independently by two reviewers and analyzed using Comprehensive Meta-Analysis V3 software.

Results: Across 33 studies encompassing 15,376 participants, ivermectin showed no significant impact on critical outcomes such as mortality [risk ratio (RR) 0.911, 95% confidence intervals (CI) 0.732-1.135], mechanical ventilation (RR 0.727, 95% CI 0.521-1.016), polymerase chain reaction conversion (RR 1.024, 95% CI 0.936-1.120), ICU admissions (RR 0.712, 95% CI 0.274-1.850), or hospitalization rates (RR 0.735, 95% CI 0.464-1.165) compared to controls. However, it significantly reduced time to symptom alleviation (standardized mean difference -0.302, 95% CI -0.587 to -0.018) and sustained symptom relief (RR 0.897, 95% CI 0.873-0.921). Adverse event (AE) rates were similar between the ivermectin and control groups (RR 0.896, 95% CI 0.797-1.007). Meta-regression indicated older age and diabetes as predictors of AEs.

Conclusion: Despite its observed benefits in symptom management, ivermectin did not significantly influence critical clinical outcomes in COVID-19 patients. These findings highlight the importance of continued research to identify effective treatments for COVID-19, emphasizing the need for high-quality studies with robust methodology to inform clinical practice and public health policy effectively.

Keywords: COVID-19; ivermectin; meta-analysis; mortality; treatment efficacy.

Figure 1.

PRISMA flow diagram showing the study selection process, including records identified, screened, assessed for eligibility, and included in the analysis, with reasons for exclusions.

Figure 2.

Forest plot showing the pooled risk ratio for all-cause mortality among COVID-19 patients treated with ivermectin versus control groups.

Figure 3.

Forest plot showing the pooled risk ratio for the requirement of mechanical ventilation in COVID-19 patients treated with ivermectin versus control groups.

Figure 4.

Forest plot showing the pooled risk ratio for PCR negative conversion among COVID-19 patients treated with ivermectin versus control groups.

Figure 5.

Forest plot showing the pooled risk ratio for sustained alleviation of symptoms in COVID-19 patients treated with ivermectin versus control groups.

Figure 6.

Forest plot showing the pooled risk ratio for ICU admission among COVID-19 patients treated with ivermectin versus control groups.

Figure 7.

Forest plot showing the pooled risk ratio for hospitalization among COVID-19 patients treated with ivermectin versus control groups.

Figure 8.

Forest plot showing the pooled risk ratio for time to alleviation of all symptoms in COVID-19 patients treated with ivermectin versus control groups.

Figure 9.

Forest plot showing the pooled risk ratio for adverse events in COVID-19 patients treated with ivermectin versus control groups.

Figure 10.

Forest plot showing the pooled risk ratio for skin rash in COVID-19 patients treated with ivermectin versus control groups.

Figure 11.

Forest plot showing the pooled risk ratio for pneumonia in COVID-19 patients treated with ivermectin versus control groups.

Figure 12.

Forest plot showing the pooled risk ratio for nausea in COVID-19 patients treated with ivermectin versus control groups.

Figure 13.

Funnel plot showing the assessment of potential publication bias for all-cause mortality among the included studies.

Figure 14.

Funnel plot showing the assessment of potential publication bias for PCR negative conversion among the included studies.

Figure 15.

Funnel plot showing the assessment of potential publication bias for adverse events among the included studies, plotting standard error versus effect size.

Figure 16.

Funnel plot showing the assessment of potential publication bias for mechanical ventilation requirement among the included studies, plotting standard error versus effect size.