Effectiveness and Toxicity of Ivermectin for the Management of COVID-19: A Meta-Analysis

Authors

DOI:

https://doi.org/10.56294/hl2025624

Keywords:

Ivermectin, COVID-19, meta-analysis, treatment outcomes, publication bias, antiviral therapy

Abstract

Ivermectin was recently suggested as a possible COVID-19 therapy, yet its clinical efficacy and safety remain controversial. This meta-analysis systematically reviews studies from the key databases of PubMed, Elsevier, Scopus, and Web of Science using the Boolean operator to effect of ivermectin on various COVID outcomes including symptom reduction, mortality, and side effects. Relevant studies’ data were included and assessed with a random-effects classicalapproximatingStandardized Mean Difference (SMD). We created forest plots to visualize the treatment effect based on several levels of COVID severity and dose and produced funnel plots to assess publication bias. The findings indicate that ivermectin does not provide a significant clinical benefit compared to standard care. Furthermore, the ivermectin group exhibited a higher incidence of adverse effects, raising safety concerns. Current evidence does not support the use of ivermectin as a primary therapy for COVID-19. Well-designed, rigorously controlled studies are essential to identify safer and more effective treatment options.

References

1. Panahi Y, Gorabi AM, Talaei S, Beiraghdar F, Akbarzadeh A, Tarhriz V, Mellatyar H. An overview on the treatment and prevention against COVID-19. Virology Journal. 2023 Feb 8;20(1):23.https://doi.org/10.1016/j.clim.2020.108427

2. Martinez MA. Efficacy of repurposed antiviral drugs: Lessons from COVID-19 . Drug discovery today. 2022 Jul 1; 27(7):1954-60. https://doi.org/10.1016/j.drudis.2022.02.01

3. Degtyarev DN. Can the SARS-COV-2 virus be considered a causative agent of TORCH infections in newborn babies? Neonatologiya: novosti, mneniya, obuchenie [Neonatology: News, Opinions, Training]. 2021;9(1):5-7. https://doi.org/10.33029/2308-2402-2021-9-1-5-7

4. Bodaghi A, Fattahi N, Ramazani A. Biomarkers: Promising and valuable tools towards diagnosis, prognosis, and treatment of COVID-19 and other diseases. Heliyon. 2023 Feb 1;9(2).https://doi.org/10.1183/16000617.0138-2021

5. Lopez Bernal, J., Andrews, N., Gower, C., Gallagher, E., Simmons, R., Thelwall, S., Stowe, J., Tessier, E., Groves, N., Dabrera, G. and Myers, R., 2021. Effectiveness of COVID-19 vaccines against the B. 1.617. 2 (Delta) variant. New England Journal of Medicine, 385(7), pp.585-594.10.1056/NEJMoa2108891

6. Andrews N, Stowe J, Kirsebom F, Toffa S, Rickeard T, Gallagher E, Gower C, Kall M, Groves N, O’Connell AM, Simons D. Effectiveness of COVID-19 vaccines against the Omicron (B. 1.1. 529) variant of concern. MedRxiv. 2021 Dec 14:2021-12.https://doi.org/10.1101/2021.12.14.21267615

7. Thompson MG, Stenehjem E, Grannis S, Ball SW, Naleway AL, Ong TC, DeSilva MB, Natarajan K, Bozio CH, Lewis N, Dascomb K. Effectiveness of COVID-19 vaccines in ambulatory and inpatient care settings. New England Journal of Medicine. 2021 Oct 7;385(15):1355-71.DOI: 10.1056/NEJMoa2110362

8. Marfe G, Perna S, Shukla AK. Effectiveness of COVID-19 vaccines and their challenges. Experimental and therapeutic medicine. 2021 Dec;22(6):1407. https://doi.org/10.3892/etm.2021.10843

9. Kavaliunas A, Ocaya P, Mumper J, Lindfeldt I, Kyhlstedt M. Swedish policy analysis for COVID-19 .Health Policy and Technology. 2020 Dec 1;9(4):598-612. https://doi.org/10.1016/j.hlpt.2020.08.009

10. Gulick RM, Pau AK, Daar E, Evans L, Gandhi RT, Tebas P, Ridzon R, Masur H, Lane HC, NIH COVID-19 Treatment Guidelines Panel, Adimora AA. National Institutes of Health COVID-19 treatment guidelines panel: perspectives and lessons learned. Annals of Internal Medicine. 2024 Nov;177(11):1547-57. https://doi.org/10.1016/j.cmi.2023.01.010

11. Ngan DK, Xu T, Xia M, Zheng W, Huang R. Repurposing drugs as COVID-19 therapies: A toxicity evaluation. Drug discovery today. 2022 Jul 1;27(7):1983-93. https://doi.org/10.1016/j.drudis.2022.04.001

12. Shirazi FM, Mirzaei R, Nakhaee S, Nejatian A, Ghafari S, Mehrpour O. Repurposing the drug, ivermectin, in COVID-19 : toxicological points of view. European Journal of Medical Research. 2022 Feb 5;27(1):21.Sakamuru, S., Huang, R. and Xia, M., 2022. Use of Tox21 Screening Data to Evaluate the COVID-19 Drug Candidates for Their Potential Toxic Effects and Related Pathways. Frontiers in Pharmacology, https://doi.org/10.1186/s40001-022-00645-8

13. Nakamura S, Huang R, Xia M. Use of Tox21 screening data to evaluate the COVID-19 drug candidates for their potential toxic effects and related pathways. Frontiers in Pharmacology. 2022 Jul 14; 13:935399. https://doi.org/10.3389/fphar.2022.935399

14. Bhimraj A, Morgan RL, Shumaker AH, Lavergne V, Baden L, Cheng VC, Edwards KM, Gandhi R, Muller WJ, O’Horo JC, Shoham S. Infectious Diseases Society of America Guidelines on the treatment and management of patients with COVID-19 (April 2020). Clinical Infectious Diseases. 2024 Jun 15;78(7):e83-102. https://doi.org/10.1093/cid/ciaa478

15. Yuan Y, Jiao B, Qu L, Yang D, Liu R. The development of COVID-19 treatment. Frontiers in immunology. 2023 Jan 26;14:1125246.https://doi.org/10.3389/fimmu.2023.1125246

16. Xie Y, Choi T, Al-Aly Z. Association of treatment with nirmatrelvir and the risk of post–COVID–19 condition. JAMA Internal Medicine. 2023 Jun 1;183(6):554-64.https://doi.org/10.1001/jamainternmed.2023.0743

17. McAfee NW, Schumacher JA, Carpenter RK, Ahmad Z. College student mental health, treatment utilization, and reduced enrollment: Findings across a state university system during the COVID-19 pandemic. Journal of American College Health. 2025 Feb 7;73(2):803-12.https://doi.org/10.1080/07448481.2023.2248495

18. Cao Z, Gao W, Bao H, Feng H, Mei S, Chen P, Gao Y, Cui Z, Zhang Q, Meng X, Gui H. VV116 versus nirmatrelvir–ritonavir for oral treatment of COVID-19 . New England Journal of Medicine. 2023 Feb 2;388(5):406-17.https://doi.org/10.1056/NEJMoa2208822

19. Konitsioti AM, Laurent S, Ellenberger D, Stahmann A, Rommer P, Haas J, Warnke C. MS treatment trends before, during, and after the COVID-19 pandemic: insights from the German MS Register. Journal of Neurology. 2025 Apr;272(4):294.https://doi.org/10.1007/s00415-025-13010-6

20. Drysdale M, Chang R, Guo T, Duh MS, Han J, Birch H, Sharpe C, Liu D, Kalia S, Van Dyke M, DerSarkissian M. Impact of treatment of COVID-19 with sotrovimab on post-acute sequelae of COVID-19 (PASC): an analysis of National COVID Cohort Collaborative (N3C) data. Infection. 2025 Mar 22:1-7.https://doi.org/10.1007/s15010-025-02505-z

21. Pourkarim F, Pourtaghi‐Anvarian S, Rezaee H. Molnupiravir: A new candidate for COVID‐19 treatment. Pharmacology research & perspectives. 2022 Feb;10(1):e00909.https://doi.org/10.1002/prp2.909

22. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, Kovalchuk E, Gonzalez A, Delos Reyes V, Martín-Quirós A, Caraco Y, Williams-Diaz A, Brown ML, Du J. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. New England Journal of Medicine. 2022 Feb 10;386(6):509-20.https://doi.org/10.1056/NEJMoa2116044

23. Lei S, Chen X, Wu J, Duan X, Men K. Small molecules in the treatment of COVID-19. Signal transduction and targeted therapy. 2022 Dec 5;7(1):387.https://doi.org/10.1038/s41392-022-01249-8

24. Wang L, Berger NA, Davis PB, Kaelber DC, Volkow ND, Xu R. COVID-19 rebound after Paxlovid and Molnupiravir during January-June 2022. MedRxiv. 2022 Jun 22.https://doi.org/10.1101/2022.06.21.22276724

25. Schulman S, Sholzberg M, Spyropoulos AC, Zarychanski R, Resnick HE, Bradbury CA, Connors JM, Falanga A, Iba T, Kaatz S, Levy JH. ISTH guidelines for antithrombotic treatment in COVID‐19. Journal of Thrombosis and Haemostasis. 2022 Oct 1;20(10):2214-25.https://doi.org/10.1111/jth.15808

26. Mazza MG, Palladini M, Poletti S, Benedetti F. Post-COVID-19 depressive symptoms: epidemiology, pathophysiology, and pharmacological treatment. CNS drugs. 2022 Jul;36(7):681-702.https://doi.org/10.1007/s40263-022-00931-3

27. Robinson PC, Liew DF, Tanner HL, Grainger JR, Dwek RA, Reisler RB, Steinman L, Feldmann M, Ho LP, Hussell T, Moss P. COVID-19 therapeutics: Challenges and directions for the future. Proceedings of the National Academy of Sciences. 2022 Apr 12;119(15):e2119893119.https://doi.org/10.1073/pnas.2119893119

28. Caraco Y, Crofoot GE, Moncada PA, Galustyan AN, Musungaie DB, Payne B, Kovalchuk E, Gonzalez A, Brown ML, Williams-Diaz A, Gao W. Phase 2/3 trial of molnupiravir for treatment of Covid-19 in nonhospitalized adults. NEJM evidence. 2022 Jan 25;1(2):EVIDoa2100043.https://doi.org/10.1056/EVIDoa2100043.

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Published

2025-08-06

How to Cite

1.
Singla A, Sudheer K, Sahu S, Mishra R, Chandna M, Mane D. Effectiveness and Toxicity of Ivermectin for the Management of COVID-19: A Meta-Analysis. Health Leadership and Quality of Life [Internet]. 2025 Aug. 6 [cited 2025 Aug. 30];4:624. Available from: https://hl.ageditor.ar/index.php/hl/article/view/624