Amiodarone seems to exhibit some antiviral activity in the disease caused by SARS-CoV-2. Here we have examined the SARS-CoV-2 disease course in the entire population of the Czech Republic and compared it with the course of the disease in patients treated with amiodarone in two major Prague's hospitals. In the whole population of the Czech Republic SARS-CoV-2 infected 1665070 persons (15.6 %) out of 10694000 (100 %) between 1 April 2020 and 30 June 2021. In the same time period only 35 patients (3.4 %) treated with amiodarone were infected with SARS-CoV-2 virus out of 1032 patients (100 %) who received amiodarone. It appears that amiodarone can prevent SARS-CoV-2 virus infection by multiple mechanisms. In in-vitro experiments it exhibits SARS-CoV-2 virus replication inhibitions. Due to its anti-inflammatory and antioxidant properties, it may have beneficial effect on the complications caused by SARS-CoV-2 as well. Additionally, inorganic iodine released from amiodarone can be converted to hypoiodite (IO-), which has antiviral and antibacterial activity, and thus can affect the life cycle of the virus.

Institute of Endocrinology Prague Czech Republic

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Andersen PI, Ianevski A, Lysvand H, Vitkauskiene A, Oksenych V, Bjoras M, Telling K, Lutsar I, Dumpis U, Irie Y, Tenson T, Kantele A, Kainov DE. Discovery and development of safe-in-man broad-spectrum antiviral agents. Int J Infect Dis. 2020;93:268–276. doi: 10.1016/j.ijid.2020.02.018. PubMed DOI PMC

Kadioglu O, Saeed M, Greten HJ, Efferth T. Identification of novel compounds against three targets of SARS CoV-2 coronavirus by combined virtual screening and supervised machine learning. Comput Biol Med. 2021;133:104359. doi: 10.1016/j.compbiomed.2021.104359. PubMed DOI PMC

Naccarelli GV, Wolbrette DL, Khan M, Bhatta L, Hynes J, Samii S, Luck J. Old and new antiarrhythmic drugs for converting and maintaining sinus rhythm in atrial fibrillation: comparative efficacy and results of trials. Am J Cardiol. 2003;91:15D–26D. doi: 10.1016/S0002-9149(02)03375-1. PubMed DOI

Narayana SK, Woods DR, Boos CJ. Management of amiodarone-related thyroid problems. Ther Adv Endocrinol Metab. 2011;2:115–126. doi: 10.1177/2042018811398516. PubMed DOI PMC

Leung AM, Braverman LE. Iodine-induced thyroid dysfunction. Curr Opin Endocrinol Diabetes Obes. 2012;19:414–419. doi: 10.1097/MED.0b013e3283565bb2. PubMed DOI PMC

Singh BN. Amiodarone as paradigm for developing new drugs for atrial fibrillation. J Cardiovasc Pharmacol. 2008;52:300–305. doi: 10.1097/FJC.0b013e31818914b6. PubMed DOI

Pollak PT, Bouillon T, Shafer SL. Population pharmacokinetics of long-term oral amiodarone therapy. Clin Pharmacol Ther. 2000;67:642–652. doi: 10.1067/mcp.2000.107047. PubMed DOI

Quaglino D, Ha HR, Duner E, Bruttomesso D, Bigler L, Follath F, Realdi G, Pettenazzo A, Baritussio A. Effects of metabolites and analogs of amiodarone on alveolar macrophages: structure-activity relationship. Am J Physiol Lung Cell Mol Physiol. 2004;287:L438–447. doi: 10.1152/ajplung.00434.2003. PubMed DOI

Sanchis-Gomar F, Lavie CJ, Morin DP, Perez-Quilis C, Laukkanen JA, Perez MV. Amiodarone in the COVID-19 Era: Treatment for symptomatic patients only, or drug to prevent infection? Am J Cardiovasc Drugs. 2020;20:413–418. doi: 10.1007/s40256-020-00429-7. PubMed DOI PMC

Gehring G, Rohrmann K, Atenchong N, Mittler E, Becker S, Dahlmann F, Pohlmann S, Vondran FW, David S, Manns MP, Ciesek S, von Hahn T. The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry. J Antimicrob Chemother. 2014;69:2123–2131. doi: 10.1093/jac/dku091. PubMed DOI PMC

Pesce L, Kopp P. Iodide transport: implications for health and disease. Int J Pediatr Endocrinol. 2014;2014:8. doi: 10.1186/1687-9856-2014-8. PubMed DOI PMC

Leung AM, Braverman LE. Consequences of excess iodine. Nat Rev Endocrinol. 2014;10:136–142. doi: 10.1038/nrendo.2013.251. PubMed DOI PMC

Martino E, Bartalena L, Bogazzi F, Braverman LE. The effects of amiodarone on the thyroid. Endocr Rev. 2001;22:240–254. doi: 10.1210/edrv.22.2.0427. PubMed DOI

Newman CM, Price A, Davies DW, Gray TA, Weetman AP. Amiodarone and the thyroid: a practical guide to the management of thyroid dysfunction induced by amiodarone therapy. Heart. 1998;79:121–127. doi: 10.1136/hrt.79.2.121. PubMed DOI PMC

Dekker BL, Touw DJ, van der Horst-Schrivers ANA, Vos MJ, Links TP, Dijck-Brouwer DAJ, Kobold ACM. Use of Salivary Iodine Concentrations to Estimate the Iodine Status of Adults in Clinical Practice. J Nutr. 2021;151:3671–3677. doi: 10.1093/jn/nxab303. PubMed DOI PMC

De la Vieja A, Santisteban P. Role of iodide metabolism in physiology and cancer. Endocr Relat Cancer. 2018;25:R225–R245. doi: 10.1530/ERC-17-0515. PubMed DOI

Aimo A, Baritussio A, Emdin M, Tascini C. Amiodarone as a possible therapy for coronavirus infection. Eur J Prev Cardiol. 2021;28:e16–e18. doi: 10.1177/2047487320919233. PubMed DOI PMC

Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Muller MA, Drosten C, Pohlmann S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271–280. doi: 10.1016/j.cell.2020.02.052. PubMed DOI PMC

Navarese EP, Musci RL, Frediani L, Gurbel PA, Kubica J. Ion channel inhibition against COVID-19: A novel target for clinical investigation. Cardiol J. 2020;27:421–424. doi: 10.5603/CJ.a2020.0090. PubMed DOI PMC

Inoue Y, Tanaka N, Tanaka Y, Inoue S, Morita K, Zhuang M, Hattori T, Sugamura K. Clathrin-dependent entry of severe acute respiratory syndrome coronavirus into target cells expressing ACE2 with the cytoplasmic tail deleted. J Virol. 2007;81:8722–8729. doi: 10.1128/JVI.00253-07. PubMed DOI PMC

Lai AL, Millet JK, Daniel S, Freed JH, Whittaker GR. The SARS-CoV fusion peptide forms an extended bipartite fusion platform that perturbs membrane order in a calcium-dependent manner. J Mol Biol. 2017;429:3875–3892. doi: 10.1016/j.jmb.2017.10.017. PubMed DOI PMC

Straus MR, Tang T, Lai AL, Flegel A, Bidon M, Freed JH, Daniel S, Whittaker GR. Ca(2+) ions promote fusion of middle east respiratory syndrome coronavirus with host cells and increase infectivity. J Virol. 2020;94:e00426. doi: 10.1128/JVI.00426-20. PubMed DOI PMC

Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol. 2015;1282:1–23. doi: 10.1007/978-1-4939-2438-7_1. PubMed DOI PMC

Salata C, Calistri A, Parolin C, Baritussio A, Palu G. Antiviral activity of cationic amphiphilic drugs. Expert Rev Anti Infect Ther. 2017;15:483–492. doi: 10.1080/14787210.2017.1305888. PubMed DOI PMC

Stadler K, Ha HR, Ciminale V, Spirli C, Saletti G, Schiavon M, Bruttomesso D, Bigler L, Follath F, Pettenazzo A, Baritussio A. Amiodarone alters late endosomes and inhibits SARS coronavirus infection at a post-endosomal level. Am J Respir Cell Mol Biol. 2008;39:142–149. doi: 10.1165/rcmb.2007-0217OC. PubMed DOI

Salata C, Baritussio A, Munegato D, Calistri A, Ha HR, Bigler L, Fabris F, Parolin C, Palu G, Mirazimi A. Amiodarone and metabolite MDEA inhibit Ebola virus infection by interfering with the viral entry process. Pathog Dis. 2015;73:ftv032. doi: 10.1093/femspd/ftv032. PubMed DOI PMC

Tang T, Bidon M, Jaimes JA, Whittaker GR, Daniel S. Coronavirus membrane fusion mechanism offers a potential target for antiviral development. Antiviral Res. 2020;178:104792. doi: 10.1016/j.antiviral.2020.104792. PubMed DOI PMC

Raffaello A, Mammucari C, Gherardi G, Rizzuto R. Calcium at the center of cell signaling: Interplay between endoplasmic reticulum, mitochondria, and lysosomes. Trends Biochem Sci. 2016;41:1035–1049. doi: 10.1016/j.tibs.2016.09.001. PubMed DOI PMC

Huotari J, Helenius A. Endosome maturation. Embo J. 2011;30:3481–3500. doi: 10.1038/emboj.2011.286. PubMed DOI PMC

Megens RT, Vijayan S, Lievens D, Doring Y, van Zandvoort MA, Grommes J, Weber C, Soehnlein O. Presence of luminal neutrophil extracellular traps in atherosclerosis. Thromb Haemost. 2012;107:597–598. doi: 10.1160/TH11-09-0650. PubMed DOI

Lippi G, Sanchis-Gomar F, Henry BM. COVID-19: unravelling the clinical progression of nature’s virtually perfect biological weapon. Ann Transl Med. 2020;8:693. doi: 10.21037/atm-20-3989. PubMed DOI PMC

Polat B, Cadirci E, Halici Z, Bayir Y, Unal D, Bilgin BC, Yuksel TN, Vancelik S. The protective effect of amiodarone in lung tissue of cecal ligation and puncture-induced septic rats: a perspective from inflammatory cytokine release and oxidative stress. Naunyn Schmiedebergs Arch Pharmacol. 2013;386:635–643. doi: 10.1007/s00210-013-0862-3. PubMed DOI

Matsumori A, Ono K, Nishio R, Nose Y, Sasayama S. Amiodarone inhibits production of tumor necrosis factor-alpha by human mononuclear cells: a possible mechanism for its effect in heart failure. Circulation. 1997;96:1386–1389. doi: 10.1161/01.CIR.96.5.1386. PubMed DOI

Heijman J, Dobrev D. Pleiotropic actions of amiodarone: still puzzling after half a century. Naunyn Schmiedebergs Arch Pharmacol. 2013;386:571–574. doi: 10.1007/s00210-013-0865-0. PubMed DOI

Nakaya H. Does anti-inflammatory action of amiodarone explain the high efficacy in patients with heart failure? Circ J. 2009;73:622–623. doi: 10.1253/circj.CJ-09-0038. PubMed DOI

Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant. 2020;39:405–407. doi: 10.1016/j.healun.2020.03.012. PubMed DOI PMC

Salata C, Munegato D, Martelli F, Parolin C, Calistri A, Baritussio A, Palu G. Amiodarone affects Ebola virus binding and entry into target cells. New Microbiol. 2018;41:162–164. PubMed

Madrid PB, Panchal RG, Warren TK, Shurtleff AC, Endsley AN, Green CE, Kolokoltsov A, Davey R, Manger ID, Gilfillan L, Bavari S, Tanga MJ. Evaluation of Ebola virus inhibitors for drug repurposing. ACS Infect Dis. 2015;1:317–326. doi: 10.1021/acsinfecdis.5b00030. PubMed DOI

Yang L, Pei RJ, Li H, Ma XN, Zhou Y, Zhu FH, He PL, Tang W, Zhang YC, Xiong J, Xiao SQ, Tong XK, Zhang B, Zuo JP. Identification of SARS-CoV-2 entry inhibitors among already approved drugs. Acta Pharmacol Sin. 2021;42:1347–1353. doi: 10.1038/s41401-020-00556-6. PubMed DOI PMC

Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S, Zhang Q, Shi X, Wang Q, Zhang L, Wang X. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 2020;581:215–220. doi: 10.1038/s41586-020-2180-5. PubMed DOI

Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H, Geng Q, Auerbach A, Li F. Structural basis of receptor recognition by SARS-CoV-2. Nature. 2020;581:221–224. doi: 10.1038/s41586-020-2179-y. PubMed DOI PMC

Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, Graham BS, McLellan JS. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367:1260–1263. doi: 10.1126/science.abb2507. PubMed DOI PMC

Perusquía M. Correlation between nongenomic action of C19-Steroids and COVID-19 severity. Physiol Res. 2021;70(Suppl 2):S135–S144. doi: 10.33549/physiolres.934789. PubMed DOI PMC

Stárka L, Dušková M. Androgens in SARS-CoV-2 coronavirus infections. Physiol Res. 2021;70(Suppl 2):S145–S151. doi: 10.33549/physiolres.934724. PubMed DOI PMC

Castaldo N, Aimo A, Castiglione V, Padalino C, Emdin M, Tascini C. Safety and efficacy of amiodarone in a patient with COVID-19. JACC Case Rep. 2020;2:1307–1310. doi: 10.1016/j.jaccas.2020.04.053. PubMed DOI PMC

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honore S, Colson P, Chabriere E, La Scola B, Rolain JM, Brouqui P, Raoult D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020;56:105949. doi: 10.1016/j.ijantimicag.2020.105949. PubMed DOI PMC

Autonomic modulation, spontaneous baroreflex sensitivity and fatigue in young men after COVID-19