Correlation between nongenomic action of C19-steroids and COVID-19 severity
Jazyk angličtina Země Česko Médium print
Typ dokumentu časopisecké články, přehledy
PubMed
34904442
PubMed Central
PMC8884366
DOI
10.33549/physiolres.934789
PII: 934789
Knihovny.cz E-zdroje
- MeSH
- androgeny krev MeSH
- COVID-19 krev diagnóza patofyziologie MeSH
- lidé MeSH
- posouzení stavu pacienta * MeSH
- stárnutí krev patologie MeSH
- svaly hladké cévní metabolismus patologie MeSH
- vazodilatace fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- androgeny MeSH
The recent COVID-19 pandemic is the defining global health crisis of our time and little is known about this disease. It has been reported that advanced age is considered a major risk factor for COVID-19 complications, and data suggest that this disease is deadlier for men than women but these observations are currently unclear. Regarding androgen action, it has been shown that certain smooth muscles are a target for androgens by inducing an acute relaxing effect in airway and vascular tissues that is nongenomically mediated; likewise, androgens are capable of inducing genomic anti-inflammatory and nongenomic hypotensive responses. The aim of this report is to associate the relationship between COVID-19 and aging men as well as the comorbidities presented in this group of patients linked with androgen deficiency. Remarkably, the nongenomic mechanisms of androgens as potential protectors are reviewed. On this basis, it is suggested that hypotestosteronemia may be a risk factor for COVID-19 severity.
Zobrazit více v PubMed
BORDALLO J, GARCÍA De BOTO MJ, MEANA C, VELASCO L, BORDALLO MC, SUÁREZ L, CANTABRANA B, SÁNCHEZ M. Modulatory role of endogenous androgens on airway smooth muscle tone in isolated guinea-pig and bovine trachea; involvement of beta2-adrenoceptors, the polyamine system and external calcium. Eur J Pharmacol. 2008;601:154–162. doi: 10.1016/j.ejphar.2008.10.039. PubMed DOI
BRODSKY IG, BALAGOPAL P, NAIR KS. Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men-a Clinical Research Center Study. J Clin Endocrinol Metab. 1996;81:3469–3475. doi: 10.1210/jcem.81.10.8855787. PubMed DOI
CAIRRAÖ E, ALVAREZ E, SANTOS-SILVA AJ, VERDE I. Potassium channels are involved in testosterone-induced vasorelaxation of human umbilical artery. Naunyn Schmiedebergs Arch Pharmacol. 2008;376:375–383. doi: 10.1007/s00210-007-0213-3. PubMed DOI
CHEN H, GUO J, WANG C, LUO F, YU X, ZHANG W, LI J, ZHAO D, XU D, GONG Q, LIAO J, YANG H, HOU W, ZHANG Y. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020a;395:809–815. doi: 10.1016/S0140-6736(20)30360-3. PubMed DOI PMC
CHEN N, ZHOU M, DONG X, QU J, GONG F, HAN Y, QIU Y, WANG J, LIU Y, WEI Y, XIA J, YU T, ZHANG X, ZHANG L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020b;395:507–513. doi: 10.1016/S0140-6736(20)30211-7. PubMed DOI PMC
CINISLIOGLU AE, CINISLIOGLU N, DEMIRDOGEN SO, SAM E, AKKAS F, ALTAY MS, UTLU M, SEN IA, YILDIRIM F, KARTAL S, AYDIN HR, KARABULUT I, OZBEY I. The relationship of serum testosterone levels with the clinical course and prognosis of COVID-19 disease in male patients: a prospective study. Andrology. 2021:1–10. doi: 10.1111/andr.13081. PubMed DOI PMC
DEENADAYALU VP, WHITE RE, STALLONE JN, GAO X, GARCIA AJ. Testosterone relaxes coronary arteries by opening the large-conductance, calcium-activated potassium channel. Am J Physiol Heart Circ Physiol. 2001;281:H1720–H1727. doi: 10.1152/ajpheart.2001.281.4.H1720. PubMed DOI
DING AQ, STALLONE JN. Testosterone-induced relaxation of rat aorta is androgen structure specific and involves K+ channel activation. J Appl Physiol. 2001;91:2742–2750. doi: 10.1152/jappl.2001.91.6.2742. PubMed DOI
DUBEY RK, OPARIL S, IMTHURN B, JACKSON EK. Sex hormones and hypertension. Cardiovasc Res. 2002;53:688–708. doi: 10.1016/s0008-6363(01)00527-2. PubMed DOI
DUŠKOVÁ M, KOLÁTOROVÁ L, ŠIMKOVÁ M, ŠRÁMKOVÁ M, MALÍKOVÁ M, HORÁČKOVÁ L, VÍTKŮ J, STÁRKA L. Steroid diagnostics of 21st century in the light of their new roles and analytical tools. Physiol Res. 2020;69(Suppl 2):S193–S203. doi: 10.33549/physiolres.934517. PubMed DOI PMC
ELBEDDINI A, TAYEFEHCHAMANI Y, YANG L. Strategies to conserve salbutamol pressurized metered-dose inhaler stock levels amid COVID-19 drug shortage. Drugs Ther Perspect. 2020:1–4. doi: 10.1007/s40267-020-00759-1. PubMed DOI PMC
ENGLISH KM, STEEDS R, JONES TH, CHANNER KS. Testosterone and coronary heart disease: is there a link? Q J Med. 1997;90:787–791. doi: 10.1093/qjmed/90.12.787. PubMed DOI
ENGLISH KM, STEEDS RP, JONES TH, DIVER MJ, CHANNER KS. Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: A randomized, double-blind, placebo-controlled study. Circulation. 2000;102:1906–1911. doi: 10.1161/01.cir.102.16.1906. PubMed DOI
ESPINOZA J, MONTAÑO LM, PERUSQUÍA M. Nongenomic bronchodilating action elicited by dehydroepiandrosterone (DHEA) in a guinea pig asthma model. J Steroid Biochem Mol Biol. 2013;138:174–182. doi: 10.1016/j.jsbmb.2013.05.009. PubMed DOI
FLORES-SOTO E, REYES-GARCÍA J, CARBAJAL-GARCÍA A, COMPUZANO-GONZÁLEZ E, PERUSQUÍA M, SOMMER B, MONTAÑO LM. Sex steroids effects on guinea pig airway smooth muscle tone and intracellular Ca2+ basal levels. Mol Cell Endocrinol. 2017;439:444–456. doi: 10.1016/j.mce.2016.10.004. PubMed DOI
GOREN A, McCOY J, WAMBIER CG, VANO-GALVÁN S, SHAPIRO J, DHURAT R, WASHENIK K, LOTTI T. What does androgenetic alopecia have to do with COVID-19? An insight into a potential new therapy. Dermatol Ther. 2020;33:e13365. doi: 10.1111/dth.13365. PubMed DOI PMC
HANSON AE, PERUSQUÍA M, STALLONE JN. Hypogonadal hypertension in male Sprague-Dawley rats is renin-angiotensin system-dependent: role of endogenous androgens. Biol Sex Differ. 2020;11:1–13. doi: 10.1186/s13293-020-00324-5. PubMed DOI PMC
HUANG C, WANG Y, LI X, REN L, ZHAO J, HU Y, ZHANG L, FAN G, XU J, GU X, ET AL. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. doi: 10.1016/S0140-6736(20)30183-5. PubMed DOI PMC
JIN JM, BAI P, HE W, WU F, LIU XF, HAN DM, LIU S, YANG JK. Gender differences in patients with COVID-19: Focus on severity and mortality. Front Public Health. 2020;8:1–6. doi: 10.3389/fpubh.2020.00152. PubMed DOI PMC
KELLY DM, JONES TH. Testosterone: a vascular hormone in health and disease. J Endocrinol. 2013;217:R47–R71. doi: 10.1530/JOE-12-0582. PubMed DOI
KHAW KT, BARRETT-CONNOR E. Blood pressure and endogenous testosterone in men: an inverse relationship. J Hypertens. 1988;6:329–332. PubMed
KOULOUMENTA V, HATZIEFTHIMIOU A, PARASKEVA E, GOURGOULIANIS K, MOLYVDAS PA. Non-genomic effect of testosterone on airway smooth muscle. Br J Pharmacol. 2006;149:1083–1091. doi: 10.1038/sj.bjp.0706936. PubMed DOI PMC
KOZIOL-WHITE CJ, GONCHAROVA EA, CAO G, JOHNSON M, KRYMSKAYA VP, PANETTIERI RA., JR DHEA-S inhibits human neutrophil and human airway smooth muscle migration. Biochim Biophys Acta. 2012;1822:1638–1642. doi: 10.1016/j.bbadis.2012.06.012. PubMed DOI PMC
LIU K, FANG YY, DENG Y, LIU W, WANG MF, MA JP, XIAO W, WANG YN, ZHONG MH, LI CH, LI GC, LIU HG. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J (Engl) 2020;133:1025–1031. doi: 10.1097/CM9.0000000000000744. PubMed DOI PMC
LORIGO M, MARIANA M, LEMOS MC, CAIRRAO E. Vascular mechanisms of testosterone: The non-genomic point of view. J Steroid Biochem Mol Biol. 2020a;196:105496. doi: 10.1016/j.jsbmb.2019.105496. PubMed DOI
LORIGO M, MARIANA M, OLIVEIRA N, LEMOS MC, CAIRRAO E. Vascular pathways of testosterone: Clinical implications. J Cardiovasc Transl Res. 2020b;13:55–72. doi: 10.1007/s12265-019-09939-5. PubMed DOI
MALEKI DANA P, SADOUGHI F, HALLAJZADEH J, ASEMI Z, MANSOURNIA MA, YOUSEFI B, MOMEN-HERAVI M. An insight into the sex differences in COVID-19 patients: What are the possible causes? Prehosp Disaster Med. 2020;35:438–441. doi: 10.1017/S1049023X20000837. PubMed DOI PMC
McCOY J, GOREN A, CADEGIANI FA, VAÑO-GALVÁN S, KOVACEVIC M, SITUM M, SHAPIRO J, SINCLAIR R, TOSTI A, STANIMIROVIC A, FONSECA D, DORNER E, COSTA ONETY D, ZIMERMAN RA, WAMBIER CG. Proxalutamide Reduces the Rate of Hospitalization for COVID-19 Male Outpatients: A Randomized Double-Blinded Placebo-Controlled Trial. Front Med. 2021:1–7. doi: 10.3389/fmed.2021.668698. PubMed DOI PMC
MIKKONEN L, PIHLAJAMAA P, SAHU B, ZHANG FP, JÄNE OA. Androgen receptor and androgen-dependent gene expression in lung. Mol Cell Endocrinol. 2010;317:14–24. doi: 10.1016/j.mce.2009.12.022. PubMed DOI
MONTAÑO LM, CALIXTO E, FIGUEROA A, FLORES-SOTO E, CARBAJAL V, PERUSQUÍA M. Relaxation of androgens on rat thoracic aorta: testosterone concentration dependent agonist/antagonist L-type Ca2+ channel activity, and 5b-dihydrotestosterone restricted to L-type Ca2+ channel blockade. Endocrinology. 2008;149:2517–2526. doi: 10.1210/en.2007-1288. PubMed DOI
MONTAÑO LM, ESPINOZA J, FLORES-SOTO E, CHÁVEZ J, PERUSQUÍA M. Androgens are bronchoactive drugs that act by relaxing airway smooth muscle and preventing bronchospasm. J Endocrinol. 2014;222:1–13. doi: 10.1530/JOE-14-0074. PubMed DOI
MONTAÑO LM, FLORES-SOTO E, SOMMER B, SOLÍS-CHAGOYÁN H, PERUSQUÍA M. Androgens are effective bronchodilators with anti-inflammatory properties: A potential alternative for asthma therapy. Steroids. 2020;153:108509. doi: 10.1016/j.steroids.2019.108509. PubMed DOI
MOORADIAN AD, MORLEY JE, KORENMAN SG. Biological actions of androgens. Endocr Rev. 1987;8:1–28. doi: 10.1210/edrv-8-1-1. PubMed DOI
MORLEY JE. Androgens and aging. Maturitas. 2001;38:61–71. doi: 10.1016/s0378-5122(00)00192-4. PubMed DOI
NIKOLICH-ZUGICH J, KNOX KS, RIOS CT, NATT B, BHATTACHARYA D, FAIN MJ. SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes. Geroscience. 2020;42:505–514. doi: 10.1007/s11357-020-00186-0. PubMed DOI PMC
ONDER G, REZZA G, BRUSAFERRO S. Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy. JAMA. 2020;323:1775–1776. doi: 10.1001/jama.2020.4683. PubMed DOI
PACES J, STRIZOVA Z, SMRZ D, CERNY J. COVID-19 and the immune system. Physiol Res. 2020;69:379–388. doi: 10.33549/physiolres.934492. PubMed DOI PMC
PANAHI L, AMIRI M, POUY S. Risks of Novel Coronavirus Disease (COVID-19) in pregnancy; a narrative review. Arch Acad Emerg Med. 2020;8:e34. PubMed PMC
PERUSQUÍA M, CONTRERAS D, HERRERA N. Hypotestosteronemia is an important factor for the development of hypertension: elevated blood pressure in orchidectomized conscious rats is reversed by different androgens. Endocrine. 2019;65:416–425. doi: 10.1007/s12020-019-01978-x. PubMed DOI
PERUSQUÍA M, ESPINOZA J, MONTAÑOLMSTALLONE JN. Regional differences in the vasorelaxing effects of testosterone and its 5-reduced metabolites in the canine vasculature. Vascul Pharmacol. 2012;56:176–182. doi: 10.1016/j.vph.2012.01.008. PubMed DOI PMC
PERUSQUÍA M, FLORES-SOTO E, SOMMER B, CAMPUZANO-GONZÁLEZ E, MARTÍNEZ-VILLA I, MARTÍNEZ-BANDERAS AI, MONTAÑO LM. Testosterone-induced relaxation involves L-type and store-operated Ca2+ channels blockade, and PGE 2 in guinea pig airway smooth muscle. Pflugers Arch. 2015;467:767–777. doi: 10.1007/s00424-014-1534-y. PubMed DOI
PERUSQUÍA M, HANSON AE, MEZA CM, KUBLI C, HERRERA N, STALLONE JN. Antihypertensive responses of vasoactive androgens in an in vivo experimental model of preeclampsia. J Steroid Biochem Mol Biol. 2018;178:65–72. doi: 10.1016/j.jsbmb.2017.11.001. PubMed DOI
PERUSQUÍA M, HERNÁNDEZ R, MONTAÑO LM, VILLALÓN CM, CAMPOS MG. Inhibitory effect of sex steroids on guinea-pig airway smooth muscle contractions. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1997;118:5–10. doi: 10.1016/s0742-8413(97)00029-7. PubMed DOI
PERUSQUÍA M, HERNÁNDEZ R, MORALES MA, CAMPOS MG, VILLALÓN CM. Role of endothelium in the vasodilating effect of progestins and androgens on the rat thoracic aorta. Gen Pharmacol. 1996;27:181–185. doi: 10.1016/0306-3623(95)00091-7. PubMed DOI
PERUSQUÍA M, HERRERA N, FERRER M, STALLONE JN. Antihypertensive effects of androgens in conscious, spontaneously hypertensive rats. J Steroid Biochem Mol Biol. 2017;167:106–114. doi: 10.1016/j.jsbmb.2016.11.016. PubMed DOI
PERUSQUÍA M, NAVARRETE E, GONZÁLEZ L, VILLALÓN CM. The modulatory role of androgens and progestins in the induction of vasorelaxation in human umbilical artery. Life Sci. 2007;81:993–1002. doi: 10.1016/j.lfs.2007.07.024. PubMed DOI
PERUSQUÍA M, STALLONE JN. Do androgens play a beneficial role in the regulation of vascular tone? Nongenomic vascular effects of testosterone metabolites. Am J Physiol Heart Circ Physiol. 2010;298:H1301–H1307. doi: 10.1152/ajpheart.00753.2009. PubMed DOI PMC
PERUSQUÍA M, VILLALÓN CM. Possible role of Ca2+ channels in the vasodilating effect of 5beta-dihydrotestosterone in rat aorta. Eur J Pharmacol. 1999;371:169–178. doi: 10.1016/s0014-2999(99)00161-2. PubMed DOI
PERUSQUÍA M. Androgen-induced vasorelaxation: a potential vascular protective effect. Exp Clin Endocrinol Diabetes. 2003;111:55–59. doi: 10.1055/s-2003-39229. PubMed DOI
PHILLIPS GB, PINKERNELL BH, JING TY. The association of hypotestosteronemia with coronary artery disease in men. Arterioscler Thromb. 1994;14:701–706. doi: 10.1161/01.atv.14.5.701. PubMed DOI
PORCHEDDU R, SERRA C, KELVIN D, KELVIN N, RUBINO S. Similarity in Case Fatality Rates (CFR) of COVID-19/SARS-COV-2 in Italy and China. J Infect Dev Ctries. 2020;14:125–128. doi: 10.3855/jidc.12600. PubMed DOI
PUGH PJ, ENGLISH KM, JONES TH, CHANNER KS. Testosterone: a natural tonic for the failing heart? Q J Med. 2000;93:689–694. doi: 10.1093/qjmed/93.10.689. PubMed DOI
RANA K, DAVEY RA, ZAJAC JD. Human androgen deficiency: insights gained from androgen receptor knockout mouse models. Asian J Androl. 2014;6:169–177. doi: 10.4103/1008-682X.122590. PubMed DOI PMC
RASTRELLI G, Di STASI V, INGLESE F, BECCARIA M, GARUTI M, Di COSTANZO D, SPREAFICO F, GRECO GF, CERVI G, PECORIELLO A. Low testosterone levels predict clinical adverse outcomes in SARS-CoV-2 pneumonia patients. Andrology. 2021;9:88–98. doi: 10.1111/andr.12821. PubMed DOI PMC
RICHARDSON S, HIRSCH JS, NARASIMHAN M, CRAWFORD JM, McGINN T, DAVIDSON KW. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020;323:2052–2059. doi: 10.1001/jama.2020.6775. PubMed DOI PMC
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;46:846–848. doi: 10.1007/s00134-020-05991-x. PubMed DOI PMC
SCHURZ H, SALIE M, TROMP G, HOAL EG, KINNEAR CJ, MÖLLER M. The X chromosome and sex-specific effects in infectious disease susceptibility. Hum Genomics. 2019;13:1–12. doi: 10.1186/s40246-018-0185-z. PubMed DOI PMC
SCRAGG JL, DALLAS ML, PEERS C. Molecular requirements for L-type Ca2+ channel blockade by testosterone. Cell Calcium. 2007;42:11–15. doi: 10.1016/j.ceca.2006.11.003. PubMed DOI
SEYREK M, IRKILATA HC, VURAL IM, YILDIRIM I, BASAL S, YILDIZ O, DAYANC M. Testosterone relaxes human internal spermatic vein through potassium channel opening action. Urology. 2011;78:P233.E1–E5. doi: 10.1016/j.urology.2011.03.003. PubMed DOI
SEYREK M, YILDIZ O, ULUSOY HB, YILDIRIM V. Testosterone relaxes isolated human radial artery by potassium channel opening action. J Pharmacol Sci. 2007;103:309–316. doi: 10.1254/jphs.FP0060883. PubMed DOI
SHAHID Z, KALAYANAMITRA R, McCLAFFERTY B, KEPKO D, RAMGOBIN D, PATEL R, AGGARWAL CS, VUNNAM R, SAHU N, BHATT D, JONES K, GOLAMARI R, JAIN R. COVID-19 and older adults: What we know. J Am Geriatr Soc. 2020;68:926–929. doi: 10.1111/jgs.16472. PubMed DOI PMC
TEP-AREENAN P, KENDALL DA, RANDALL MD. Testosterone-induced vasorelaxation in the rat mesenteric arterial bed is mediated predominantly via potassium channels. Br J Pharmacol. 2002;135:735–740. doi: 10.1038/sj.bjp.0704522. PubMed DOI PMC
TRAISH AM, GUAY A, FEELEY R, SAAD F. The dark side of testosterone deficiency: I. Metabolic syndrome and erectile dysfunction. J Androl. 2009;30:10–22. doi: 10.2164/jandrol.108.005215. PubMed DOI
TRAISH AM, KANG HP, SAAD F, GUAY AT. Dehydroepiandrosterone (DHEA)--a precursor steroid or an active hormone in human physiology. J Sex Med. 2011;8:2960–2982. doi: 10.1111/j.1743-6109.2011.02523.x. PubMed DOI
URBAN RJ, BODENBURGYHGILKISON C, FOXWORTH J, COGGAN AR, WOLFE RR, FERRANDO A. Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am J Physiol. 1995;269:E820–E826. doi: 10.1152/ajpendo.1995.269.5.E820. PubMed DOI
WAMBIER CG, GOREN A. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to be androgen mediated. J Am Acad Dermatol. 2020;83:308–309. doi: 10.1016/j.jaad.2020.04.032. PubMed DOI PMC
WANG C, JACKSON G, JONES TH, MATSUMOTO AM, NEHRA A, PERELMAN MA, SWERDLOFF RS, TRAISH A, ZITZMANN M, CUNNINGHAM G. Low testosterone associated with obesity and the metabolic syndrome contributes to sexual dysfunction and cardiovascular disease risk in men with type 2 diabetes. Diabetes Care. 2011;34:1669–1675. doi: 10.2337/dc10-2339. PubMed DOI PMC
WANG D, HU B, HU C, ZHU F, LIU X, ZHANG J, WANG B, XIANG H, CHENG Z, XIONG Y, ZHAO Y, LI Y, WANG X, PENG Z. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323:1061–1069. doi: 10.1001/jama.2020.1585. PubMed DOI PMC
WEBB CM, McNEILL JG, HAYWARD CS, De ZEIGLER D, COLLINS P. Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease. Circulation. 1999;100:1690–1696. doi: 10.1161/01.CIR.100.16.1690. PubMed DOI
WU JT, LEUNG K, BUSHMAN M, KISHORE N, NIEHUS R, De SALAZAR PM, COWLING BJ, LIPSITCH M, LEUNG GM. Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan, China. Nat Med. 2020;26:506–510. doi: 10.1038/s41591-020-0822-7. PubMed DOI PMC
YILDIZ O, SEYREK M, IRKILATA HC, YILDIRIM I, TAHMAZ L, DAYANC M. Testosterone might cause relaxation of human corpus cavernosum by potassium channel opening action. Urology. 2009;74:229–232. doi: 10.1016/j.urology.2008.12.022. PubMed DOI
ZHENG F, LIAO C, FAN QH, CHEN H, ZHAO X, XIE Z, LI X, CHEN C, LU X, LIU Z, ET AL. Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China. Curr Med Sci. 2020;40:275–280. doi: 10.1007/s11596-020-2172-6. PubMed DOI PMC
ZHOU F, YU T, DU R, FAN G, LIU Y, LIU Z, XIANG J, WANG Y, SONG B, GU X, ET AL. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062. doi: 10.1016/S0140-6736(20)30566-3. PubMed DOI PMC
Antiviral activity of amiodarone in SARS-CoV-2 disease