A critical analysis about the supposed role of azithromycin in the treatment of covid-19
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Published:
Dec 22, 2021
Keywords:
anti-infective agents, azithromycin, covid-19, SARS-CoV-2
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Abstract
After over one year, the coronavirus disease 2019 (covid-19) has still affected millions of people. For this reason, global efforts to promote better treatment of covid-19 have been undertaken focused on the repurposing of existing medications.In Brazil, azithromycin, a broad-spectrum antibiotic, has been used in association with other drugs as an immunomodulatory, anti-inflammatory, and anti-viral agent, regardless of bacterial co-infection. Indeed, data from experimental studies have demonstrated the capacity of this drug in reducing the production of infection-induced pro-inflammatory cytokines, such as IL-8, IL-6, and TNF-alpha. However, observational studies revealed conflicting results regarding its effect, whereas well-conducted clinical trials have not shown a considerable effect of this agent on the improvement of clinical outcomes. This narrative review addressed the possible role of this antibiotic in the management of covid-19, based on data from clinical and preclinical studies.
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1.
Santana RR, Barbosa BO, Soares JR de O, Colombo RM, Santos VR, Amaral RG, Andrade LN. A critical analysis about the supposed role of azithromycin in the treatment of covid-19. Health Sci J [Internet]. 2021Dec.22 [cited 2024May4];11(4):11-. Available from: https://portalrcs.hcitajuba.org.br/index.php/rcsfmit_zero/article/view/1184
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NARRATIVE REVIEW
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6. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19) A Review. JAMA. 2020;323(18):1824-36. https://doi.org/10.1001/jama.2020.6019 PMCid:PMC7492917
7. Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, et al. Extrapulmonary manifestations of COVID-19. Nat Med. 2020;26(7):1017-32. https://doi.org/10.1038/s41591-020-0968-3 PMid:32651579
8. Kanoh S, Rubin BK. Mechanisms of action and clinical application of macrolides as immunomodulatory medications. Clin Microbiol Rev. 2010;23(3):590-615. https://doi.org/10.1128/CMR.00078-09 PMid:20610825 PMCid:PMC2901655
9. Min JY, Jang YJ. Macrolide therapy in respiratory viral infections. Mediators Inflamm. 2012;2012:649570. https://doi.org/10.1155/2012/649570 PMid:22719178 PMCid:PMC3375106
10. Echeverría-Esnal D, Martin-Ontiyuelo C, Navarrete-Rouco ME, De-Antonio Cuscó M, Ferrández O, Horcajada JP, Grau S. Azithromycin in the treatment of COVID-19: a review. Expert Rev Anti Infec Ther. 2021;19(2):147-63. https://doi.org/10.1080/14787210.2020.1813024 PMid:32853038
11. Jensen S, Thomsen AR. Sensing of RNA viruses: a review of innate immune receptors involved in recognizing RNA virus invasion. J Virol. 2012;86(6):2900-10. https://doi.org/10.1128/JVI.05738-11 PMid:22258243 PMCid:PMC3302314
12. Chen X, Yang X, Zheng Y, Yang Y, Xing Y, Chen Z. SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex. Protein Cell. 2014;5(5):369-81. https://doi.org/10.1007/s13238-014-0026-3 PMid:24622840 PMCid:PMC3996160
13. Henry BM, Vikse J, Benoit S, Favaloro EJ, Lippi G. Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis. Clin Chim Acta. 2020;507:167-73. ]https://doi.org/10.1016/j.cca.2020.04.027 PMid:32348783 PMCid:PMC7195008
14. Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol. 2020;20(6):355-62. https://doi.org/10.1038/s41577-020-0331-4 PMid:32376901 PMCid:PMC7201395
15. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033-4. https://doi.org/10.1016/S0140-6736(20)30628-0
16. Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, Madison JA, et al. Neutrophil extracellular traps in COVID-19. JCI Insight. 2020;5(11):e138999. https://doi.org/10.1172/jci.insight.138999
17. Kasal DA, De Lorenzo A, Tibiriçá E. COVID-19 and microvascular disease: pathophysiology of SARS-CoV-2 infection with focus on the renin-angiotensin system. Heart Lung Circ. 2020;29(11):1596-602. https://doi.org/10.1016/j.hlc.2020.08.010 PMid:32972810 PMCid:PMC7467122
18. Barnes BJ, Adrover JM, Baxter-Stoltzfus A, Borczuk A, Cools-Lartigue J, Crawford JM, et al. Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med. 2020;217(6):e20200652. https://doi.org/10.1084/jem.20200652 PMid:32302401 PMCid:PMC7161085
19. Vardhana SA, Wolchok JD. The many faces of the anti-COVID immune response. J Exp Med. 2020;217(6):e20200678. https://doi.org/10.1084/jem.20200678 PMid:32353870 PMCid:PMC7191310
20. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19) A Review. JAMA. 2020;324(8):782-93. https://doi.org/10.1001/jama.2020.12839 PMid:32648899
21. Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis. 2020;71(15):762-8. https://doi.org/10.1093/cid/ciaa248 PMid:32161940 PMCid:PMC7108125
22. Sreepadmanabh M, Sahu AK, Chande A. COVID-19: Advances in diagnostic tools, treatment strategies, and vaccine development. J Biosci. 2020;45(1):148. https://doi.org/10.1007/s12038-020-00114-6 PMid:33410425 PMCid:PMC7683586
23. Bakheit AH, Al-Hadiya BM, Abd-Elgalil AA. Azithromycin. Profiles Drug Subst Excip Relat Methodol. 2014;39:1-40. https://doi.org/10.1016/B978-0-12-800173-8.00001-5 PMid:24794904
24. Li H, Liu DH, Chen LL, Zhao Q, Yu YZ, Ding JJ, et al. Meta-analysis of the adverse effects of long-term azithromycin use in patients with chronic lung diseases. Antimicrob Agents Chemother. 2014;58(1):511-7. https://doi.org/10.1128/AAC.02067-13 PMid:24189261 PMCid:PMC3910718
25. Bosnar M, Čužić S, Bošnjak B, Nujić K, Ergović G, Marjanović N, et al. Azithromycin inhibits macrophage interleukin-1B production through inhibition of activator protein-1 in lipoplysaccharide induced murine pulmonary neutorphilia. Int Immunopharmacol. 2011;11(4):424-34. https://doi.org/10.1016/j.intimp.2010.12.010 PMid:21195124
26. Murphy DM, Forrest IA, Corris PA, Johnson GE, Small T, Jones D, et al. Azithromycin attenuates effects of lipopolysaccharide on lung allograft bronchial epithelial cells. J Heart Lung Transp. 2008;27(11):1210-6. https://doi.org/10.1016/j.healun.2008.07.026 PMid:18971093
27. Lin SJ, Kuo ML, Hsiao HS, Lee PT. Azithromycin modulates immune response of human monocyte-derived dendritic cells and CD4 + T cells. Int Immunopharmacol. 2016;40:318-326. https://doi.org/10.1016/j.intimp.2016.09.012 PMid:27664570
28. Tsai WC, Rodriguez ML, Young KS, Deng JC, Thannickal VJ, Tateda K, et al. Azithromycin blocks neutrophil recruitment in Pseudomonas endobronchial infection. Am J Respir Crit Care Med. 2004;170(12):1331-9. https://doi.org/10.1164/rccm.200402-200OC PMid:15361366
29. Gielen V, Johnston SL, Edwards MR. Azithromycin induces anti-viral responses in bronchial epithelial cells. Eur Respir J. 2010;36(3):646-54. https://doi.org/10.1183/09031936.00095809 PMid:20150207
30. Oliver ME, Hinks TSC. Azithromycin in viral infections. Rev Med Virol. 2021;31(2):e2163. https://doi.org/10.1002/rmv.2163 PMid:32969125 PMCid:PMC7536932
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