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

DOI record: { "DOI": "10.1101/2021.04.30.21256415", "URL": "http://dx.doi.org/10.1101/2021.04.30.21256415", "abstract": "<jats:title>Abstract</jats:title><jats:sec><jats:title>Importance</jats:title><jats:p>Repurposing Ivermectin, a known anti-parasitic 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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We conducted a systematic search for full-text manuscripts published from February 1, 2020, to August 15th, 2021 focusing on Ivermectin therapy against COVID-19. The primary outcomes were mortality, need for intensive care unit (ICU) admission; 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 all analyses.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We included a total of 52 studies (n=17561) in the qualitative analysis, out of these, 44 studies (n=14019) were included in the meta-analysis. In the mortality meta-analysis (N=29), odds of death were lower in the Ivermectin-arm compared to control (OR 0.54, p=0.009). Although lower odds of mortality were observed in various subgroup analyses of RCTs, they did not reach statistical significance: therapeutic RCTs: mild-moderate COVID-19 (OR 0.31, p=0.06), therapeutic RCTs: severe/critical COVID-19 (OR 0.86, p=0.56), inpatient RCTs: mild-moderate COVID-19 (OR 0.18, p=0.08), inpatient RCTs: severe/critical COVID-19 (OR 0.86, p=0.56). Ivermectin, mostly as adjuvant therapy, was associated with higher odds of viral clearance (N=22) (OR 3.52, p=0.0002), shorter duration to achieve viral clearance (N=8) (MD - 4.12, p=0.02), reduced need for hospitalization (N=6) (OR 0.34, p=008).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our meta-analysis suggests that the mortality benefit of Ivermectin in COVID-19 is uncertain. But as adjuvant therapy, Ivermectin may improve viral clearance and reduce the need for hospitalization.</jats:p></jats:sec><jats:sec><jats:title>Highlights</jats:title><jats:sec><jats:title>What We Already Know about This Topic</jats:title><jats:list list-type=\"order\"><jats:list-item><jats:p>COVID-19 is an ongoing global pandemic, for which Ivermectin has been tried on a therapeutic and prophylactic basis.</jats:p></jats:list-item><jats:list-item><jats:p>Results from several clinical trials and observational studies suggest that Ivermectin may improve survival and clinical outcomes with a good safety profile when compared with other treatments; however, the current evidence is limited..</jats:p></jats:list-item></jats:list></jats:sec><jats:sec><jats:title>What This Article Tells Us That Is New</jats:title><jats:list list-type=\"order\"><jats:list-item><jats:p>This systematic review and meta-analysis provide a summary of the latest literature on the efficacy and safety of Ivermectin use for COVID-19.</jats:p></jats:list-item><jats:list-item><jats:p>Based on our analysis of the latest evidence, we found that Ivermectin’s benefit in reducing mortality cannot be concluded with confidence. However, as an adjuvant therapy it may help reduce the need for hospitalization, duration for viral clearance while increasing the likelihood of achieving viral clearance.</jats:p></jats:list-item><jats:list-item><jats:p>We need more high-quality data for conclusive evidence regarding the benefit of Ivermectin in reducing the need for ICU admissions, mechanical ventilation and duration of hospital stay in COVID-19 patients.</jats:p></jats:list-item></jats:list></jats:sec></jats:sec>", "accepted": { "date-parts": [ [ 2021, 9, 17 ] ] }, "author": [ { "affiliation": [], "family": "Karale", "given": "Smruti", "sequence": "first" }, { "ORCID": "http://orcid.org/0000-0001-6047-5559", "affiliation": [], "authenticated-orcid": false, "family": "Bansal", "given": "Vikas", "sequence": "additional" }, { "affiliation": [], "family": "Makadia", "given": "Janaki", "sequence": "additional" }, { "affiliation": [], "family": "Tayyeb", "given": "Muhammad", "sequence": "additional" }, { "affiliation": [], "family": "Khan", "given": "Hira", "sequence": "additional" }, { "affiliation": [], "family": "Ghanta", "given": "Shree Spandana", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0003-3777-5670", "affiliation": [], "authenticated-orcid": false, "family": "Singh", "given": "Romil", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-1891-2118", "affiliation": [], "authenticated-orcid": false, "family": "Tekin", "given": "Aysun", "sequence": "additional" }, { "affiliation": [], "family": "Bhurwal", "given": "Abhishek", "sequence": "additional" }, { "affiliation": [], "family": "Mutneja", "given": "Hemant", "sequence": "additional" }, { "affiliation": [], "family": "Mehra", "given": "Ishita", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-4383-3411", "affiliation": [], "authenticated-orcid": false, "family": "Kashyap", "given": "Rahul", "sequence": "additional" } ], "container-title": [], "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2021, 5, 6 ] ], "date-time": "2021-05-06T16:08:53Z", "timestamp": 1620317333000 }, "deposited": { "date-parts": [ [ 2021, 9, 20 ] ], "date-time": "2021-09-20T08:59:03Z", "timestamp": 1632128343000 }, "group-title": "Infectious Diseases (except HIV/AIDS)", "indexed": { "date-parts": [ [ 2024, 5, 1 ] ], "date-time": "2024-05-01T16:17:29Z", "timestamp": 1714580249537 }, "institution": [ { "name": "medRxiv" } ], "is-referenced-by-count": 10, "issued": { "date-parts": [ [ 2021, 5, 4 ] ] }, "link": [ { "URL": "https://syndication.highwire.org/content/doi/10.1101/2021.04.30.21256415", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "246", "original-title": [], "posted": { "date-parts": [ [ 2021, 5, 4 ] ] }, "prefix": "10.1101", "published": { "date-parts": [ [ 2021, 5, 4 ] ] }, "publisher": "Cold Spring Harbor Laboratory", "reference": [ { "DOI": "10.23750/abm.v91i1.9397", "doi-asserted-by": "publisher", "key": "2021092001550866000_2021.04.30.21256415v2.1" }, { "DOI": "10.1016/S1473-3099(20)30120-1", "doi-asserted-by": "publisher", "key": "2021092001550866000_2021.04.30.21256415v2.2" }, { "key": "2021092001550866000_2021.04.30.21256415v2.3", "unstructured": "Domecq JP , Lal A , Sheldrick CR , et al. 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