LETTER


Can Ivermectin be Useful for COVID-19 Management as an Immunomodulating Agent?



Sergey Sheleg1, *
iD

1 Phoenix VA Health Care System, 650 E Indian School Rd., Phoenix, AZ 85012, U.S.A.


© 2020 Sergey Sheleg.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Phoenix VA Health Care System, 650 E Indian School Rd., Phoenix, AZ 85012, U.S.A.; E-mail: ssheleg@yahoo.com


Abstract

The possibility of using ivermectin in the treatment of COVID-19 as an immunomodulating agent, has been discussed, which may prevent life-threatening virally driven cytokine storm syndrome.

Keywords: COVID-19, Ivermectin, NF-kB, Cytokine, Cytokine storm syndrome, Immunomodulator.



Dear Editor,

COVID-19 is an emerging and rapidly evolving situation in the world.

The recent report of Caly et al., (2020) [1] stated that an anti-parasitic medicine ivermectin has antiviral action against the SARS-CoV-2 virus (a causative agent for COVID-19) clinical isolate in vitro and it is worthy of further consideration as a possible SARS-CoV-2 antiviral drug.

Ivermectin is a well-known anti-parasitic drug with a broad spectrum of activity, high efficacy as well as a wide margin of safety [2].

It is approved by the U.S. FDA for managing such parasitic infections like strongyloidiasis and onchocerciasis [3]. Evidence suggests that oral ivermectin may be a safe and effective treatment for scabies as well; however, ivermectin is not U.S. FDA-approved for this use [4].

Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome [5].

Predictors of fatality from a recent retrospective, multicenter study of 150 confirmed COVID-19 cases in Wuhan (China) suggest that mortality might be due to virally driven hyperinflammation [6].

The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivo-

tal mediator of inflammatory responses. NF-κB induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokines [7].

Jiang et al., (2019) in their study found that ivermectin at its very low dose, which did not induce obvious cytotoxicity, drastically reversed the resistance of tumor cells to the chemotherapeutic drugs both in vitro and in vivo by inhibition of the transcriptional factor NF-κB and could potentially be used in combination with chemotherapeutic agents to treat cancers and in particular, drug-resistant cancers [8]. Prior to them, Zhang et al., (2009) indicated that ivermectin might inhibit lipopolysaccharide (LPS)-induced production of inflammatory cytokines by blocking the NF-κB pathway and improving LPS-induced survival in mice [9].

Summarizing all the information, ivermectin could be considered for a clinical trial to determine its efficacy in the management of COVID-19 as an immunomodulating agent which might prevent life-threatening virally driven cytokine storm syndrome.

REFERENCES

[1] Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res 2020; 178: 104787.
[2] González Canga A, Sahagún Prieto AM, Diez Liébana MJ, Fernández Martínez N, Sierra Vega M, García Vieitez JJ. The pharmacokinetics and interactions of ivermectin in humans--a mini-review. AAPS J 2008; 10(1): 42-6.
[3] NDA 50-742/S-022 stromectol® (ivermectin) Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050742s022lbl.pdf
[4] Currie BJ, McCarthy JS. Permethrin and ivermectin for scabies. N Engl J Med 2010; 362(8): 717-25.
[5] Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395(10229): 1033-4.
[6] Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020. published online March 3 2020
[7] Liu T, Zhang L, Joo D, Sun S-C. NF-κB signaling in inflammation. Signal Transduct Target Ther 2017; 2: 17023.
[8] Jiang L, Wang P, Sun YJ, Wu YJ. Ivermectin reverses the drug resistance in cancer cells through EGFR/ERK/Akt/NF-κB pathway. J Exp Clin Cancer Res 2019; 38(1): 265.
[9] 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(11): 524-9.