Use of ivermectin in the treatment of COVID-19 in humans: integrative review

Authors

DOI:

https://doi.org/10.33448/rsd-v10i12.20835

Keywords:

Ivermectin; COVID-19; Treatment; Clinical studies.

Abstract

With the appearance of the first cases of infection by SARS-CoV-2, the WHO quickly declared a pandemic against COVID-19, due to the high speed and transmissibility of the disease. In this scenario, in addition to research for the development of new drugs and vaccines, existing and approved drugs have also been studied, through the repositioning of drugs, as an alternative for the treatment of COVID-19, as is the case with ivermectin. Since then, several clinical trials have been carried out around the world to evaluate the antiviral action of ivermectin against COVID-19. Thus, this integrative review aims to analyze the scientific literature dealing with clinical trials on the use of ivermectin as a treatment for COVID-19, describing the works, as well as discussing their results and limitations. The search for scientific studies published in electronic databases: PubMed, LILACS and SciELO was carried out, using the keywords “IVERMECTIN and COVID-19” and “IVERMECTIN and SARS-COV-2”. Articles published from 2019 onwards, which worked on the use of ivermectin as a treatment for COVID-19, were selected. The research found studies that showed both positive and negative results for the use of ivermectin in relation to some parameters of the treatment of COVID-19. However, the works in general have methodological limitations. Thus, current evidence on the use of this drug to treat patients with COVID-19 is inconclusive, indicating the need for further well-designed and structured clinical trials to confirm or rule out these findings.

References

Abbott (2021). Bula para o profissional de saúde. Revectina. Recuperado de https://dam.abbott.com/pt-br/documents/pdfs/nossas-bulas/r/BU-16-Revectina-bula-profissional-final.pdf

Abd-Elsalam, S., Noor, R. A., Badawi, R., Khalaf, M., Esmail, E. S., Soliman, S., Abd El Ghafar, M. S., Elbahnasawy, M., Moustafa, E. F., Hassany, S. M., Medhat, M. A., Ramadan, H. K., Eldeen, M., Alboraie, M., Cordie, A., & Esmat, G. (2021). Clinical study evaluating the efficacy of ivermectin in COVID-19 treatment: A randomized controlled study. Journal of medical virology, 93(10), 5833–5838. https://doi.org/10.1002/jmv.27122

Ahmed, S., Karim, M. M., Ross, A. G., Hossain, M. S., Clemens, J. D., Sumiya, M. K., Phru, C. S., Rahman, M., Zaman, K., Somani, J., Yasmin, R., Hasnat, M. A., Kabir, A., Aziz, A. B., & Khan, W. A. (2021). A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness. International journal of infectious, 103, 214–216. https://doi.org/10.1016/j.ijid.2020.11.191

Caly, L., Druce, J. D., Catton, M. G., Jans, D. A., & Wagstaff, K. M. (2020). The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral research, 178, 104787. https://doi.org/10.1016/j.antiviral.2020.104787

Chaccour, C., Casellas, A., Blanco-Di Matteo, A., Pineda, I., Fernandez-Montero, A., Ruiz-Castillo, P., Richardson, M. A., Rodríguez-Mateos, M., Jordán-Iborra, C., Brew, J., Carmona-Torre, F., Giráldez, M., Laso, E., Gabaldón-Figueira, J. C., Dobaño, C., Moncunill, G., Yuste, J. R., Del Pozo, J. L., Rabinovich, N. R., Schöning, V., … Fernández-Alonso, M. (2021). The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial. EClinicalMedicine, 32, 100720. https://doi.org/10.1016/j.eclinm.2020.100720

Camprubí, D., Almuedo-Riera, A., Martí-Soler, H., Soriano, A., Hurtado, J. C., Subirà, C., Grau-Pujol, B., Krolewiecki, A., & Muñoz, J. (2020). Lack of efficacy of standard doses of ivermectin in severe COVID-19 patients. PloS one, 15(11), e0242184. https://doi.org/10.1371/journal.pone.0242184

Dos Santos W. G. (2020). Natural history of COVID-19 and current knowledge on treatment therapeutic options. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 129, 110493. https://doi.org/10.1016/j.biopha.2020.110493

Elalfy, H., Besheer, T., El-Mesery, A., El-Gilany, A. H., Soliman, M. A., Alhawarey, A., Alegezy, M., Elhadidy, T., Hewidy, A. A., Zaghloul, H., Neamatallah, M., Raafat, D., El-Emshaty, W. M., Abo El Kheir, N. Y., & El-Bendary, M. (2021). Effect of a combination of nitazoxanide, ribavirin, and ivermectin plus zinc supplement (MANS.NRIZ study) on the clearance of mild COVID-19. Journal of medical virology, 93(5), 3176–3183. https://doi.org/10.1002/jmv.26880

European Medicines Agency. (2021). COVID-19 treatments: authorised. Recuperado de https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines/treatments-covid-19/covid-19-treatments-authorised

Fonseca, S. N. S., de Queiroz Sousa, A., Wolkoff, A. G., Moreira, M. S., Pinto, B. C., Valente Takeda, C. F., Rebouças, E., Vasconcellos Abdon, A. P., Nascimento, A., & Risch, H. A. (2020). Risk of hospitalization for Covid-19 outpatients treated with various drug regimens in Brazil: Comparative analysis. Travel medicine and infectious disease, 38, 101906. https://doi.org/10.1016/j.tmaid.2020.101906

Food and Drug Administration. (2021). Why You Should Not Use Ivermectin to Treat or Prevent COVID-19. Recuperado de https://www.fda.gov/consumers/consumer-updates/why-you-should-not-use-ivermectin-treat-or-prevent-covid-19

Galan, L., Santos, N., Asato, M. S., Araújo, J. V., de Lima Moreira, A., Araújo, A., Paiva, A., Portella, D., Marques, F., Silva, G., de Sousa Resende, J., Tizolim, M. R., Santos, P. L., Buttenbender, S. F., de Andrade, S. B., Carbonell, R., Da Rocha, J. G., de Souza, R., & da Fonseca, A. J. (2021). Phase 2 randomized study on chloroquine, hydroxychloroquine or ivermectin in hospitalized patients with severe manifestations of SARS-CoV-2 infection. Pathogens and global health, 115(4), 235–242. https://doi.org/10.1080/20477724.2021.1890887

Guo, Y. R., Cao, Q. D., Hong, Z. S., Tan, Y. Y., Chen, S. D., Jin, H. J., Tan, K. S., Wang, D. Y., & Yan, Y. (2020). The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Military Medical Research, 7(1), 11. https://doi.org/10.1186/s40779-020-00240-0

Hamed, M. A. (2020). An overview on COVID-19: reality and expectation. Bull Natl Res Cent. 44(1):86. doi: 10.1186/s42269-020-00341-9.

Heidary, F., & Gharebaghi, R. (2020) Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen. The Journal of Antibiotics 73, 593–602. https://doi.org/10.1038/s41429-020-0336-z

Jans, D. A., & Wagstaff, K. M. (2020). Ivermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal?. Cells, 9(9), 2100. https://doi.org/10.3390/cells9092100

Kaur, H., Shekhar, N., Sharma, S., Sarma, P., Prakash, A., & Medhi, B. (2021). Ivermectin as a potential drug for treatment of COVID-19: an in-sync review with clinical and computational attributes. Pharmacological reports : PR, 73(3), 736–749. https://doi.org/10.1007/s43440-020-00195-y

Khan, M., Khan, M., Debnath, C. R., Nath, P. N., Mahtab, M. A., Nabeka, H., Matsuda, S., & Akbar, S. (2020). Ivermectin Treatment May Improve the Prognosis of Patients With COVID-19. Archivos de bronconeumologia, 56(12), 828–830. https://doi.org/10.1016/j.arbres.2020.08.007

Köche, J. C. (2011). Fundamentos de metodologia científica: teoria da ciência e iniciação à pesquisa. Petrópolis, RJ: Vozes.

Li, N., Zhao, L., & Zhan, X. (2020). Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. Cell Physiol, 236, 2959–2975. https://doi.org/10.1002/jcp.30055

Lima-Morales, R., Méndez-Hernández, P., Flores, Y. N., Osorno-Romero, P., Sancho-Hernández, C. R., Cuecuecha-Rugerio, E., Nava-Zamora, A., Hernández-Galdamez, D. R., Romo-Dueñas, D. K., & Salmerón, J. (2021). Effectiveness of a multidrug therapy consisting of Ivermectin, Azithromycin, Montelukast, and Acetylsalicylic acid to prevent hospitalization and death among ambulatory COVID-19 cases in Tlaxcala, Mexico. International journal of infectious diseases, 105, 598–605. https://doi.org/10.1016/j.ijid.2021.02.014

Lima, W. G., Brito, J., Overhage, J., & Nizer, W. (2020). The potential of drug repositioning as a short-term strategy for the control and treatment of COVID-19 (SARS-CoV-2): a systematic review. Archives of virology, 165(8), 1729–1737. https://doi.org/10.1007/s00705-020-04693-5

López-Medina, E., López, P., Hurtado, I. C., Dávalos, D. M., Ramirez, O., Martínez, E., Díazgranados, J. A., Oñate, J. M., Chavarriaga, H., Herrera, S., Parra, B., Libreros, G., Jaramillo, R., Avendaño, A. C., Toro, D. F., Torres, M., Lesmes, M. C., Rios, C. A., & Caicedo, I. (2021). Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial. JAMA, 325(14), 1426–1435. https://doi.org/10.1001/jama.2021.3071

Mahmud, R., Rahman, M. M., Alam, I., Ahmed, K., Kabir, A., Sayeed, S., Rassel, M. A., Monayem, F. B., Islam, M. S., Islam, M. M., Barshan, A. D., Hoque, M. M., Mallik, M. U., Yusuf, M. A., & Hossain, M. Z. (2021). Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial. The Journal of international medical research, 49(5). https://doi.org/10.1177/03000605211013550

Melo, J. R. R.; Duarte, E. C.; Moraes, M. V.; Fleck, K. & Arrais, P. S. D. (2021). Automedicação e uso indiscriminado de medicamentos durante a pandemia da COVID-19. Cad. Saúde Pública 37(4). doi: 10.1590/0102-311X00053221

Mendes, K. D. S., Silveira, R. C. de C. P., & Galvão, C. M. (2019). Uso De Gerenciador De Referências Bibliográficas Na Seleção Dos Estudos Primários Em Revisão Integrativa. Texto & Contexto - Enfermagem, 28. https://doi.org/10.1590/1980-265x-tce-2017-0204

Ministério da Saúde. (2021). Ivermectina para o tratamento de pacientes com COVID-19. Recuperado de https://www.gov.br/saude/pt-br/coronavirus/publicacoes-tecnicas/notas-tecnicas/nota-tecnica-ivermectina-covid-19

Mishra, S. K., & Tripathi, T. (2021). One year update on the COVID-19 pandemic: Where are we now?. Acta tropica, 214, 105778. https://doi.org/10.1016/j.actatropica.2020.105778

Molento M. B. (2020). COVID-19 and the rush for self-medication and self-dosing with ivermectin: A word of caution. One health (Amsterdam, Netherlands), 10, 100148. https://doi.org/10.1016/j.onehlt.2020.100148

National Institute of Health. (2021). Antiviral Drugs That Are Approved or Under Evaluation for the Treatment of COVID-19. Recuperado de https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/

Pan American Health Organization. (2021). Ongoing Living Update of COVID-19 Therapeutic Options: Summary of Evidence. Rapid Review, 6 May 2021. Recuperado de https://iris.paho.org/bitstream/handle/10665.2/52719/PAHOIMSEIHCOVID-1921015_eng.pdf?sequence=39&isAllowed=y

Pandey, S., Pathak, S. K., Pandey, A., Salunke, A. A., Chawla, J., Sharma, A., Sharma, S., Thivari, P., & Ratna, H. (2020). Ivermectin in COVID-19: What do we know?. Diabetes & metabolic syndrome, 14(6), 1921–1922. https://doi.org/10.1016/j.dsx.2020.09.027

Portmann-Baracco, A., Bryce-Alberti, M., & Accinelli, R. A. (2020). Antiviral and Anti-Inflammatory Properties of Ivermectin and Its Potential Use in COVID-19. Propiedades antivirales y antiinflamatorias de ivermectina y su potencial uso en COVID-19. Archivos de bronconeumologia, 56(12), 831. https://doi.org/10.1016/j.arbres.2020.06.011

Pott-Junior, H., Bastos Paoliello, M. M., Miguel, A., da Cunha, A. F., de Melo Freire, C. C., Neves, F. F., da Silva de Avó, L. R., Roscani, M. G., Dos Santos, S. S., & Chachá, S. (2021). Use of ivermectin in the treatment of Covid-19: A pilot trial. Toxicology reports, 8, 505–510. https://doi.org/10.1016/j.toxrep.2021.03.003

Rajter, J. C., Sherman, M. S., Fatteh, N., Vogel, F., Sacks, J., & Rajter, J. J. (2021). Use of Ivermectin Is Associated With Lower Mortality in Hospitalized Patients With Coronavirus Disease 2019: The Ivermectin in COVID Nineteen Study. Chest, 159(1), 85–92. https://doi.org/10.1016/j.chest.2020.10.009

Samaddar, A., Grover, M., & Nag, V. L. (2020). Pathophysiology and Potential Therapeutic Candidates for COVID-19: A Poorly Understood Arena. Frontiers in pharmacology, 11, 585888. https://doi.org/10.3389/fphar.2020.585888

Schmith, V. D., Zhou, J. J., & Lohmer, L. (2020). The Approved Dose of Ivermectin Alone is not the Ideal Dose for the Treatment of COVID-19. Clinical pharmacology and therapeutics, 108(4), 762–765. https://doi.org/10.1002/cpt.1889

Shahbaznejad, L., Davoudi, A., Eslami, G., Markowitz, J. S., Navaeifar, M. R., Hosseinzadeh, F., Movahedi, F. S., & Rezai, M. S. (2021). Effects of Ivermectin in Patients With COVID-19: A Multicenter, Double-Blind, Randomized, Controlled Clinical Trial. Clinical. Therapeutics. https://doi.org/10.1016/j.clinthera.2021.04.007

Sharun, K., Shyamkumar, T. S., Aneesha, V. A., Dhama, K., Pawde, A. M., & Pal, A. (2019). Current therapeutic applications and pharmacokinetic modulations of ivermectin. Veterinary world, 12(8), 1204–1211. https://doi.org/10.14202/vetworld.2019.1204-1211

Souza, M. T., Silva, M. D., & Carvalho, R. (2010). Revisão integrativa: o que é e como fazer Integrative review: what is it? How to do it? Einstein 8(1), 102-106. https://doi.org/10.1590/S1679-45082010RW1134

Trivedi, N., Verma, A., & Kumar, D. (2020). Possible treatment and strategies for COVID-19: review and assessment. European review for medical and pharmacological sciences, 24(23), 12593–12608. https://doi.org/10.26355/eurrev_202012_24057

World Health Organization. (2021). Weekly operational update on COVID-19 31 May 2021. Recuperado de https://www.who.int/publications/m/item/weekly-operational-update-on-covid-19-31-may-2021

Wulan, W. N., Heydet, D., Walker, E. J., Gahan, M. E., & Ghildyal, R. (2015). Nucleocytoplasmic transport of nucleocapsid proteins of enveloped RNA viruses. Frontiers in microbiology, 6, 553. https://doi.org/10.3389/fmicb.2015.00553

Xavier, A. R., Silva, J. S., Almeida, J. P. C. L., Conceição, J. F. F., Lacerda, G. S., & Kannan, S. (2020). COVID-19: manifestações clínicas e laboratoriais na infecção pelo novo coronavírus. J Bras Patol Med Lab, 56 (1), 1-9. https://doi.org/10.5935/1676-2444.20200049

Published

01/10/2021

How to Cite

MACIEL, N.; NEIS , V. B.; TENFEN , A. Use of ivermectin in the treatment of COVID-19 in humans: integrative review. Research, Society and Development, [S. l.], v. 10, n. 12, p. e564101220835, 2021. DOI: 10.33448/rsd-v10i12.20835. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/20835. Acesso em: 22 nov. 2024.

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Section

Review Article