Ivermectin to treat COVID-19

Drugs

In the fight against COVID-19, in addition to the development of successful vaccines, researchers have been investigating potential treatment options. Since drug development is typically a lengthy process, many research groups have investigated the potential for existing drugs to be repurposed for treating COVID-19. For example, remdesivir was one of the first drugs repurposed in the fight against COVID-19.

Another treatment gaining significant attention is ivermectin. Ivermectin is an anti-parasitic medication typically used to treat roundworm infections.

Since ivermectin is considered inexpensive and relatively safe, it has been suggested as a treatment for COVID-19. This assumption is backed by the fact that some research studies have shown that ivermectin has antiviral effects in cell studies in the lab1 – led to the off-label use of ivermectin to treat COVID-19.

It is important to understand that studies in the laboratory may not predict or correlate to real-world results in people. There are several reasons for this, including the doses used and the types of cells it was tested in. This is why clinical trials are necessary to understand the effects of ivermectin in patients with COVID-19.

What’s the evidence for Ivermectin to treat COVID-19?

Using publicly available databases researchers in one study were able to separate countries according to their routine use of ivermectin. The researchers then looked at how many confirmed COVID-19 cases per 100,000 people these countries had reported.2 The researchers noted that countries that use ivermectin routinely as a preventive medication had reported lower rates of COVID-19. According to the researchers, this provides further evidence that ivermectin could protect against COVID-19 infection.2

Another study reviewed the hospital records of patients who were hospitalized with COVID-19.3 The study looked back over the records of patients from four hospitals in Florida in early 2020. Some of these patients had been treated with ivermectin and some had been treated without ivermectin. It is important to note that most patients were also treated with azithromycin and/or hydroxychloroquine.

The study reported reduced death rates in patients who received ivermectin. The researchers conclude that although these results are promising, that they need to be confirmed in larger, randomized controlled trials before ivermectin can be recommended to treat COVID-19.3

These studies, however, were not clinical trials – or more specifically – were not randomized controlled clinical trials, which are considered the ‘gold standard’ of clinical studies to demonstrate whether a particular treatment is effective or safe.

What do the Ivermectin clinical trials report?

A randomized controlled trial compared ivermectin treatment to ivermectin plus doxycycline, or a placebo (no treatment) group of patients hospitalized with COVID-19.4 The trial reported that symptoms of COVID-19 (that is cough, fever, and sore throat) were not significantly different no matter which treatment the patients had. However, the trial reported that viral clearance occurred earlier in the ivermectin-treated patients. The researchers suggest that more trials are necessary to build on these initial results.4

In another trial of hospitalized patients, ivermectin was compared with chloroquine and hydroxychloroquine to treat severe COVID-19.5 The trial reported similar deaths occurred in all three groups. Also, the treatments did not have any effect on whether patients required oxygen or ventilation and did not make any difference in terms of ICU admissions.5

In patients with mild COVID-19, a randomized clinical trial reported that patients who were given a five-day course of ivermectin did not have a significant difference in symptoms when compared with patients who did not receive ivermectin treatment.6 The trial reported that the time until symptoms resolved was not different if patients received ivermectin or not.6

Another trial of mild COVID-19 investigated whether a single dose of ivermectin could reduce the transmission of the SARS-CoV-2 virus if patients were treated as soon as they tested positive.7 This trial reported a reduction in viral load in patients who received ivermectin on days four and seven after treatment; however, these results were not statistically significant. The researchers suggest larger clinical trials to further investigate these results.7

When assessing the elimination of the virus from the body, one trial compared the time it took to eliminate the virus and the amount of viral elimination when patients were given a combination treatment that included ivermectin plus three other treatments at the same time (nitazoxanide, ribavirin, and zinc).8 This trial reported a shorter time to viral clearance from the nasopharynx (nose and throat) in the treatment group.8

Two different doses of ivermectin were compared to treatment with the antivirals lopinavir/ritonavir in another clinical trial.9 This trial reported a significant reduction in days until patients tested negative for the virus in the ivermectin-treated patients. These patients also had higher SPO2% (blood oxygen) levels and higher platelet count.9

Future studies

There are multiple clinical trials using ivermectin to treat COVID-19 underway worldwide – including in the US, Italy, Spain, Israel, India, Egypt, Argentina, and Brazil.10 These trials will provide valuable information for the use of ivermectin in the fight against COVID-19.

References:

  1. Caly L., Druce J.D., Catton M.G., Jans D.A., Wagstaff K.M. The FDA-approved drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antivir. Res. 2020;178:104787. doi: 10.1016/j.antiviral.2020.104787.
  2. Hellwig, M. D., & Maia, A. (2021). A COVID-19 prophylaxis? Lower incidence associated with prophylactic administration of ivermectin. International journal of antimicrobial agents57(1), 106248. https://doi.org/10.1016/j.ijantimicag.2020.106248
  • 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. Chest159(1), 85–92. https://doi.org/10.1016/j.chest.2020.10.009
  • 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 diseases : IJID : official publication of the International Society for Infectious Diseases103, 214–216. https://doi.org/10.1016/j.ijid.2020.11.191
  • Galan LEB, Santos NMD, Asato MS, Araújo JV, de Lima Moreira A, Araújo AMM, Paiva ADP, Portella DGS, Marques FSS, Silva GMA, de Sousa Resende J, Tizolim MR, Santos PL, Buttenbender SF, de Andrade SB, Carbonell RCC, Da Rocha JG, de Souza RGS, da Fonseca AJ. Phase 2 randomized study on chloroquine, hydroxychloroquine or ivermectin in hospitalized patients with severe manifestations of SARS-CoV-2 infection. Pathog Glob Health. 2021 Mar 8:1-8. doi: 10.1080/20477724.2021.1890887. Epub ahead of print. PMID: 33682640; PMCID: PMC7938655.
  • López-Medina E, López P, Hurtado IC, Dávalos DM, Ramirez O, Martínez E, Díazgranados JA, Oñate JM, Chavarriaga H, Herrera S, Parra B, Libreros G, Jaramillo R, Avendaño AC, Toro DF, Torres M, Lesmes MC, Rios CA, Caicedo I. Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial. JAMA. 2021 Mar 4:e213071. doi: 10.1001/jama.2021.3071. Epub ahead of print. PMID: 33662102; PMCID: PMC7934083.
  • Chaccour C, Casellas A, Blanco-Di Matteo A, Pineda I, Fernandez-Montero A, Ruiz-Castillo P, Richardson MA, Rodríguez-Mateos M, Jordán-Iborra C, Brew J, Carmona-Torre F, Giráldez M, Laso E, Gabaldón-Figueira JC, Dobaño C, Moncunill G, Yuste JR, Del Pozo JL, Rabinovich NR, Schöning V, Hammann F, Reina G, Sadaba B, Fernández-Alonso M. 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 Feb;32:100720. doi: 10.1016/j.eclinm.2020.100720. Epub 2021 Jan 19. PMID: 33495752; PMCID: PMC7816625.
  • Elalfy H, Besheer T, El-Mesery A, El-Gilany AH, Abd Elazez MS, Alhawarey A, Alegezy M, Elhadidy T, Hewidy AA, Zaghloul H, Neamatallah MAM, Raafat D, El-Emshaty WM, Abo El Kheir NY, El-Bendary M. Effect of a combination of nitazoxanide, ribavirin, and ivermectin plus zinc supplement (MANS.NRIZ study) on the clearance of mild COVID-19. J Med Virol. 2021 Feb 16. doi: 10.1002/jmv.26880. Epub ahead of print. PMID: 33590901.
  • Babalola OE, Bode CO, Ajayi AA, Alakaloko FM, Akase IE, Otrofanowei E, Salu OB, Adeyemo WL, Ademuyiwa AO, Omilabu S. Ivermectin shows clinical benefits in mild to moderate COVID19: A randomised controlled double-blind, dose-response study in Lagos. QJM. 2021 Feb 18:hcab035. doi: 10.1093/qjmed/hcab035. Epub ahead of print. PMID: 33599247; PMCID: PMC7928689.
  1. Formiga, F. R., Leblanc, R., de Souza Rebouças, J., Farias, L. P., de Oliveira, R. N., & Pena, L. (2021). Ivermectin: an award-winning drug with expected antiviral activity against COVID-19. Journal of controlled release : official journal of the Controlled Release Society329, 758–761. https://doi.org/10.1016/j.jconrel.2020.10.009
  2. Image by PIRO4D from Pixabay 

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