https://doi.org/10.4081/monaldi.2022.2062
The effect of ivermectin on non-severe and severe COVID-19 disease and gender-based difference of its effectiveness
Submitted: August 25, 2021
Accepted: January 13, 2022
Published: January 18, 2022
Accepted: January 13, 2022
Abstract Views: 3045
PDF: 2135
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
The COVID-19 pandemic has led to mortality and morbidity since December 2019. Many possible treatment options have been advised till date. The role of ivermectin in the treatment of COVID-19 disease remains controversial. The aim of our study was to evaluate the effect of ivermectin in hospitalized patients with non-severe and severe COVID-19 disease. We conducted a retrospective cohort study that compared outcomes in 2 groups of COVID-19 patients hospitalized at the largest tertiary care center of Pakistan. The study group was given ivermectin along with standard treatment of covid-19 disease; the comparison group was not. Data on mortality, inflammatory markers such as C-reactive protein (CRP) and ferritin, length of hospital stay and baseline characteristics were collected from Aga Khan University’s database from October 2020 till February 2021. Statistical analysis was done to determine the effectiveness of ivermectin in non-severe and severe COVID-19. Comparison of effectiveness of Ivermectin in both the genders was also conducted. The cohort included 188 patients out of which 90 were treated with ivermectin. Mortality and length of hospitalization was not found to be significantly different in the study group compared with the control group (5.6% vs 5.1%; p=0.87 and 5 days vs 4 days; p=0.27). Analysis of secondary outcomes did not yield statistically significant results, apart from ferritin levels which were significantly less in patients treated with ivermectin (547.1 vs 756.7; p=0.03). The ferritin and CRP levels in affected males were higher than in females on admission and discharge. Our findings suggest ivermectin does not significantly affect all-cause mortality, length of hospitalization and CRP levels in hospitalized COVID-19 patients. Large scale randomized controlled trials (RCTs) are required to further evaluate the role of ivermectin in covid-19 disease.
World Health Organization. Weekly epidemiological update on COVID-19. Available from: https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---18-may-2021
Government of Pakistan. COVID-19 Health Advisory Platform by Ministry of National Health Services Regulations & Coordination 2021. Available from: https://covid.gov.pk/stats/pakistan
Pan H, Peto R, Henao-Restrepo AM, et al. Repurposed antiviral drugs for Covid-19 - Interim WHO solidarity trial results. N Engl J Med 2021;38:497-511.
Hermine O, Mariette X, Tharaux PL, et al. Effect of tocilizumab vs usual care in adults hospitalized with COVID-19 and moderate or severe pneumonia: A randomized clinical trial. JAMA Intern Med 2021;181:32-40.
Agarwal A, Mukherjee A, Kumar G, et al. Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial). BMJ 2020;371:m3939.
Tufan A, Avanoğlu Güler A, Matucci-Cerinic M. COVID-19, immune system response, hyperinflammation and repurposing antirheumatic drugs. Turk J Med Sci 2020;50:620-32.
Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 2021;384:693-704.
Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus remdesivir for hospitalized adults with Covid-19. N Engl J Med 2021;384:795-807.
Yang SNY, Atkinson SC, Wang C, et al. The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer. Antiviral Res 2020;177:104760.
Wang X, Lv C, Ji X, et al. Ivermectin treatment inhibits the replication of Porcine circovirus 2 (PCV2) in vitro and mitigates the impact of viral infection in piglets. Virus Res 2019;263:80-6.
Priel A, Silberberg SD. Mechanism of ivermectin facilitation of human P2X4 receptor channels. J Gen Physiol 2004;123:281-93.
Zhang X, Song Y, Ci X, et al. Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice. Inflamm Res 2008;57:524-9.
Caly L, Druce JD, Catton MG, et al. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res 2020;178:104787.
Eurekalert [Internet]. Latest peer-reviewed research: Immediate global ivermectin use will end COVID-19 pandemic (2021, May 7). Last accessed on 19th July 2021. https://eurekalert.org/pub_releases/2021-05/fccc-lpr050621.php
No authors listed. Update to living WHO guideline on drugs for covid-19. BMJ 2021;372:n860.
Rajter JC, Sherman MS, Fatteh N, et al. Use of ivermectin is associated with lower mortality in hospitalized patients with coronavirus disease 2019: the ivermectin in COVID nineteen study. Chest 2021;159:85-92.
Chaccour C, Casellas A, Blanco-Di Matteo A, et al. 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 2021;32:100720.
López-Medina E, López P, Hurtado IC, et al. Effect of ivermectin on time to resolution of symptoms among adults with mild COVID-19: A randomized clinical trial. JAMA 2021;325:1426-35.
Ahmed Elgazzar BH, Shaimaa Abo Youssef, Basma Hany, et al. Efficacy and safety of ivermectin for treatment and prophylaxis of COVID-19 pandemic. Research Square 2021 (Withdrawn). Available from: https://assets.researchsquare.com/files/rs-100956/v2/c11416a2-d0bd-494f-abc8-3cbf8c605b10.pdf?c=1631861037
Morteza Shakhsi N, Nematollah G, Peyman N, et al. Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial. Research Square 2021. Available from: https://www.researchsquare.com/article/rs-109670/v1
Ravikirti, Roy R, Pattadar C, et al. Ivermectin as a potential treatment for mild to moderate COVID-19 – A double blind randomized placebo-controlled trial. medRxiv 2021:2021.01.05.21249310.
Gorial FI, Mashhadani S, Sayaly HM, et al. Effectiveness of ivermectin as add-on therapy in COVID-19 management (Pilot Trial). medRxiv 2020:2020.07.07.20145979.
Chachar AZK, Kahn KA, Asif M, et al. Effectiveness of ivermectin in SARS-CoV-2/COVID-19 patients. Int J Sci 2020;9:31-5.
National Institutes of Health. Table 2c. Ivermectin: Selected Clinical Data: NIH; 2021. Updated 11 February 2021. Available from: https://www.covid19treatmentguidelines.nih.gov/tables/table-2c/
Camprubí D, Almuedo-Riera A, Martí-Soler H, et al. Lack of efficacy of standard doses of ivermectin in severe COVID-19 patients. PLoS One 2020;15:e0242184.
Wimmersberger D, Coulibaly JT, Schulz JD, et al. Efficacy and safety of ivermectin against trichuris trichiura in preschool-aged and school-aged children: A randomized controlled dose-finding trial. Clin Infect Dis 2018;67:1247-55.
Smit MR, Ochomo EO, Aljayyoussi G, et al. Human direct skin feeding versus membrane feeding to assess the mosquitocidal efficacy of high-dose ivermectin (IVERMAL Trial). Clin Infect Dis 2019;69:1112-9.
Buonfrate D, Salas-Coronas J, Muñoz J, et al. Multiple-dose versus single-dose ivermectin for Strongyloides stercoralis infection (Strong Treat 1 to 4): a multicentre, open-label, phase 3, randomised controlled superiority trial. Lancet Infect Dis 2019;19):1181-90.
European Medicine Agency. EMA advises against use of ivermectin for the prevention or treatment COVID-19 outside randomised clinical trials. 2021, March 22. Last accessed on 19th July 2021. Available from: https://www.ema.europa.eu/en/news/ema-advises-against-use-ivermectin-prevention-treatment-covid-19-outside-randomised-clinical-trials
National Institutes of Health. COVID-19 treatment. Ivermectin. Available from: www.covid19treatmentguidelines.nih.gov/antiviral-therapy/ivermectin/
Padhy BM, Mohanty RR, Das S, Meher BR. Therapeutic potential of ivermectin as add on treatment in COVID 19: A systematic review and meta-analysis. J Pharm Pharm Sci 2020;23:462-9.
Okumuş N, Demirtürk N, Çetinkaya RA, et al. Evaluation of the effectiveness and safety of adding ivermectin to treatment in severe COVID-19 patients. BMC Infect Dis 2021;21:411.
Lepist EI, Phan TK, Roy A, et al. Cobicistat boosts the intestinal absorption of transport substrates, including HIV protease inhibitors and GS-7340, in vitro. Antimicrob Agents Chemother 2012;56:5409-13.
Drewe J, Gutmann H, Fricker G, et al. HIV protease inhibitor ritonavir: a more potent inhibitor of P-glycoprotein than the cyclosporine analog SDZ PSC 833. Biochem Pharmacol 1999;57:1147-52.
Hampton T. Insight on sex-based immunity differences, with COVID-19 implications. JAMA 2020;324:1274.
Haitao T, Vermunt JV, Abeykoon J, et al. COVID-19 and sex differences: Mechanisms and biomarkers. Mayo Clin Proc 2020;95:2189-203.
Takahashi T, Iwasaki A. Sex differences in immune responses. Science 2021;371:347348.
Jin JM, Bai P, He W, et al. Gender differences in patients with COVID-19: Focus on severity and mortality. Front Public Health 2020;8:152.
Mangia C, Russo A, Civitelli S, et al. [Sex/gender differences in COVID-19 lethality: what the data say, and do not say].[Article in Italian]. Epidemiol Prev 2020;44:400-6.
Vahidy FS, Pan AP, Ahnstedt H, et al. Sex differences in susceptibility, severity, and outcomes of coronavirus disease 2019: Cross-sectional analysis from a diverse US metropolitan area. PLoS One 2021;16:e0245556.
Oudit GY, Pfeffer MA. Plasma angiotensin-converting enzyme 2: novel biomarker in heart failure with implications for COVID-19. Eur Heart J 2020;41:1818-20.
Galasso V, Pons V, Profeta P, et al. Gender differences in COVID-19 attitudes and behavior: Panel evidence from eight countries. Proc Natl Acad Sci USA 2020;117:27285-91.
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-62.
Zhou B, She J, Wang Y, et al. Utility of ferritin, procalcitonin, and C-reactive protein in severe patients with 2019 novel coronavirus disease. Research Square 2020. Available from: https://www.researchsquare.com/article/rs-18079/v1
Abbaspour N, Hurrell R, Kelishadi R. Review on iron and its importance for human health. J Res Med Sci 2014;19:164.
Ahmed S, Karim MM, Ross AG, et al. A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness. Int J Infect Dis 2021;103:214-6.
How to Cite
Zubair, Syed Muhammad, Muhammad Waleed Chaudhry, Ali Bin Sarwar Zubairi, Talha Shahzad, Aqusa Zahid, Ibrahim Ali Khan, Javaid Ahmed Khan, and Muhammad Irfan. 2022. “The Effect of Ivermectin on Non-Severe and Severe COVID-19 Disease and Gender-Based Difference of Its Effectiveness”. Monaldi Archives for Chest Disease 92 (4). https://doi.org/10.4081/monaldi.2022.2062.
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