CLINICAL OUTCOMES ASSOCIATED WITH IVERMECTIN USE IN COVID-19: AN UPDATED SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Despite exhaustive efforts by the global healthcare to treat COVID-19, the death toll continues to rise. Ivermectin, a known anti-parasitic agent, when re-purposed for treating COVID-19, has demonstrated positive results in several studies. We aim to evaluate the benefit and risk of Ivermectin therapy in COVID-19 patients. METHODS: We conducted a systematic search for full-text manuscripts published from February 1, 2020, to August 15, 2021, that focused on the efficacy and safety of Ivermectin use in COVID-19. Overall mortality and need for intensive care unit (ICU) admission were primary outcomes;secondary outcomes were adverse effects, need for mechanical ventilation, viral clearance, time to viral clearance, need for hospitalization, and length of hospital stay. Random-effects models were used for the quantitative and qualitative analyses. RESULTS: A total of 52 studies (n= 17561) were included in the qualitative analysis and out of these, 44 studies (n=14019) were included in the quantitative analysis. In the qualitative analysis of Ivermectin treatment, a mortality rate of 3.6%, ICU admission rate of 5.4%, mechanical ventilation rate of 3.9%, and adverse event rate of 6.6% were observed. In the overall mortality meta-analysis, odds of death were lower in the Ivermectin-arm compared to the non-Ivermectin arm (OR 0.54, p=0.009). However, in the subgroup analysis of 15 randomized controlled trials, we observed lower odds of mortality in the mild/moderate sub-group (OR 0.31, p=0.06) but without statistical significance. In the severe/critical sub-group, odds were only marginally lowered and were not statistically significant.(OR 0.86, p=0.56). The benefit with Ivermectin was not statistically significant in the meta-analysis of the need for ICU admission (OR 0.48, p=0.17), mechanical ventilation (OR=0.75, p=0.12) and duration of hospitalization (MD -1.80, p= 0.06). The meta-analysis of adverse effects was inconclusive (OR 0.87, p=0.30). Ivermectin, frequently used as adjunctive treatment, was linked with higher odds of achieving viral clearance (OR 3.52, p=0.0002), in a shorter duration (MD -4.12, p=0.02) as well as reduction in the need for hospitalization (OR 0.34, p=0.008). CONCLUSIONS: In the updated quantitative analysis, we found that mortality benefit with Ivermectin treatment is uncertain. Trends of decreased need for ICU admissions and mechanical ventilation, and duration of hospitalization were observed but were not significant. Mostly as an adjuvant treatment, Ivermectin may help accelerate viral clearance as well as reduce the need for hospitalization. Meta-analysis for adverse events suggested that there may be no difference in the adverse event rate with Ivermectin and other treatments, but this cannot be concluded with confidence. The qualitative analysis showed that Ivermectin led to better clinical outcomes in COVID-19 patients and a lower incidence of adverse events. CLINICAL IMPLICATIONS: Well-designed larger observational studies and clinical trials are needed to confirm Ivermectin's mortality benefit in COVID-19 and to further investigate its ideal dosage and timing in the disease course, drug interactions, and possible synergistic drug combinations to achieve maximum benefit. We also need to evaluate the impact of Ivermectin in patients infected with the newly emerging strains and its role in vaccinated patients. Finally, we recommend physicians to exercise caution while prescribing Ivermectin for COVID-19 while we await evidence-based guidelines. DISCLOSURES: No relevant relationships by Vikas Bansal, source=Web Response No relevant relationships by Abhishek Bhurwal, source=Web Response No relevant relationships by Shree Spandana Ghanta, source=Web Response No relevant relationships by Smruti Karale, source=Web Response No relevant relationships by Rahul Kashyap, source=Web Response No relevant relationships by Hira Khan, source=Web Response No relevant relationships by Janaki Makadia, source=Web Response No relevant relationsh ps by Ishita Mehra, source=Web Response No relevant relationships by HEMANT MUTNEJA, source=Web Response No relevant relationships by ROMIL SINGH, source=Web Response No relevant relationships by Muhammad Tayyeb, source=Web Response No relevant relationships by Aysun Tekin, source=Web Response