A Meta-analysis of Mortality, Need for ICU admission, Use of Mechanical Ventilation and Adverse Effects with Ivermectin Use in COVID-19 Patients

Karale, S.; Bansal, V.; Makadia, J.; Tayyeb, M.; Khan, H.; Ghanta, S. S.; Singh, R.; Tekin, A.; Bhurwal, A.; Mutneja, H.; Mehra, I.; Kashyap, R.

Importance/Background: Despite the global healthcare's exhaustive efforts to treat COVID-19, we still do not have an effective cure for it. Repurposing Ivermectin, a known antiparasitic agent, for treating COVID-19 has demonstrated positive results in several studies. We aim to evaluate the benefit and risk of Ivermectin in COVID-19. Methods: We conducted a systematic search for full-text manuscripts published from February 1, 2020 to March 27, 2021 that focused on efficacy and safety of Ivermectin therapy against COVID-19. The primary outcomes were overall mortality, need for intensive care unit (ICU) admission; secondary outcomes were - adverse effects, need for mechanical ventilation. Random-effects models were used for all analysis. Results: We included a total of 38 studies (n=15,002) in the qualitative analysis (Mortality N=28, ICU admission= 8, Mechanical Ventilation= 10, Adverse events=28) and out of these, 30 studies (n=11,291) were included in the quantitative analysis (Mortality N=22, ICU admission= 5, Mechanical Ventilation= 9, Adverse events=17). In the mortality meta-analysis, odds of death were lower in the Ivermectin-arm compared to the non-Ivermectin arm. (OR 0.39, 95% CI 0.22-0.70; I2=81%). Subgroup analysis of 12 randomized controlled trials with severity-based data showed mortality benefit overall (OR 0.33, 95% CI 0.15-0.72; I2=53%) and in the mild/moderate sub-group (OR 0.10, 95% CI 0.03-0.33; I2=0%). Benefit of Ivermectin in decreasing; the need for ICU admission (OR 0.48, 95% CI 0.17-1.37; I2=59%) and mechanical ventilation (OR 0.64, 95% CI 0.40-1.04; I2=17%) was not significant. The quantitative analysis of adverse effects with Ivermectin use was inconclusive (OR 0.92, 95% CI 0.64-1.33; I2=14%). Conclusion: Our meta-analysis suggests that Ivermectin could be an effective adjuvant therapy in reducing mortality, particularly in patients with mild-moderate clinical presentation of COVID-19. Trends of decreased need for ICU admissions and mechanical ventilation were observed but were not significant. The analysis for adverse effects was inconclusive.