Coronavirus disease 2019 or COVID-19 has rapidly emerged as a global pandemic. This viral infection involves the upper respiratory tract and could lead to severe pneumonia with respiratory distress or even death. Certain studies have found higher initial plasma levels of most pro-inflammatory cytokines during the course of the infection. In this context, both in vitro and in vivo studies have revealed that metronidazole could decrease the levels of several cytokines, which are known to increase during the COVID-19 infection, including interleukin (IL)8, IL6, IL1B, tumor necrosis factor (TNF)α, IL12, IL1α, and interferon (IFN)γ, as well as the levels of C-reactive protein (CRP) and neutrophil count.
Furthermore, the drug could decrease neutrophil-generated reactive oxygen species during inflammation. Metronidazole could counteract majority of the immunopathological manifestations of the COVID-19 infection. Therefore, studies with a large sample size are required to determine the efficacy of metronidazole in the treatment of COVID-19 infection.
Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-3.
Reviglio VE, Osaba M, Reviglio V, ChiaradiaP, Kuo IC, O’Brien TP. COVID-19 and Ophthalmology: A New Chapter in an Old Story. Med Hypothesis Discov Innov Ophthalmol. 2020 Summer; 9(2): 71-73.
Bai Y, Yao L, Wei T, Tian F, Jin D-Y, Chen L, et al. Presumed asymptomatic carrier transmission of COVID-19. Jama. 2020.
Wu D, Yang XO. TH17 Responses in Cytokine Storm of COVID-19: An Emerging Target of JAK2 Inhibitor Fedratinib. Journal of Microbiology, Immunology and Infection. 2020.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020;395(10223):497-506.
Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet. 2020;395(10223):507-13.
Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol. 2020.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020.
Sisson G, Jeong J-Y, Goodwin A, Bryden L, Rossler N, Lim-Morrison S, et al. Metronidazole Activation Is Mutagenic and Causes DNA Fragmentation in Helicobacter pylori and inEscherichia coli Containing a Cloned H. pylori rdxA+(Nitroreductase) Gene. Journal of Bacteriology. 2000;182(18):5091-6.
Yudin MH, Landers DV, Meyn L, Hillier SL. Clinical and cervical cytokine response to treatment with oral or vaginal metronidazole for bacterial vaginosis during pregnancy: a randomized trial. Obstetrics & Gynecology. 2003;102(3):527-34.
Shakir L, Javeed A, Ashraf M, Riaz A. Metronidazole and the immune system. Die Pharmazie-An International Journal of Pharmaceutical Sciences. 2011;66(6):393-8.
Bayraktar MR, Mehmet N, Durmaz R. Serum cytokine changes in Turkish children infected with Giardia lamblia with and without allergy: Effect of metronidazole treatment. Acta tropica. 2005;95(2):116-22.
Rizzo A, Paolillo R, Guida L, Annunziata M, Bevilacqua N, Tufano MA. Effect of metronidazole and modulation of cytokine production on human periodontal ligament cells. International immunopharmacology. 2010;10(7):744-50.
Fitzpatrick LR, Small J, Hoerr RA, Bostwick EF, Maines L, Koltun WA. In vitro and in vivo effects of the probiotic Escherichia coli strain M-17: immunomodulation and attenuation of murine colitis. British journal of nutrition. 2008;100(3):530-41.
Amar S, Wu S-c, Madan M. Is Porphyromonas gingivalis cell invasion required for atherogenesis? Pharmacotherapeutic implications. The Journal of Immunology. 2009;182(3):1584-92.
Mercer‐Jones M, Hadjiminas D, Heinzelmann M, Peyton J, Cook M, Cheadle W. Continuous antibiotic treatment for experimental abdominal sepsis: effects on organ inflammatory cytokine expression and neutrophil sequestration. British journal of surgery. 1998;85(3):385-9.
Fararjeh M, Mohammad MK, Bustanji Y, AlKhatib H, Abdalla S. Evaluation of immunosuppression induced by metronidazole in Balb/c mice and human peripheral blood lymphocytes. International immunopharmacology. 2008;8(2):341-50.
Lefebvre Y, Hesseltine HC. The peripheral white blood cells and metronidazole. Jama. 1965;194(1):15-8.
Elizondo G, Montero R, Herrera JE, Hong E, Ostrosky-Wegman P. Lymphocyte proliferation kinetics and sister-chromatid exchanges in individuals treated with metronidazole. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 1994;305(2):133-7.
Akamatsu H, Oguchi M, Nishijima S, Asada Y, Takahashi M, Ushijima T, et al. The inhibition of free radical generation by human neutrophils through the synergistic effects of metronidazole with palmitoleic acid: a possible mechanism of action of metronidazole in rosacea and acne. Archives of dermatological research. 1990;282(7):449-54.
Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. Journal of Pharmaceutical Analysis. 2020.