{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T18:55:15Z","timestamp":1773860115070,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T00:00:00Z","timestamp":1592438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Current data suggest that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing corona virus disease-19 (COVID-19) seems to follow a more severe clinical course in patients with cardiovascular disease (CVD), hypertension, and overweight\/obesity. It appears that lipid-lowering pharmacological interventions, in particular statins, might reduce the risk of cardiovascular complications caused by COVID-19 and might potentially have an additional antiviral activity. It has been shown that high cholesterol levels are associated with more lipid rafts, subdomains of the plasma membrane that can harbour angiotensin-converting enzyme 2 (ACE2) receptors for the S-protein of SARS-CoV-2. Evidence of the importance of cholesterol for viral entry into host cells could suggest a role for cholesterol-lowering therapies in reducing viral infectivity. In addition to their lipid-lowering and plaque-stabilisation effects, statins possess pleiotropic effects including anti-inflammatory, immunomodulatory, and antithrombotic activities. Lower rates of mortality and intubation have been reported in studies investigating statin therapy in influenza infection, and statin therapy was shown to increase viral clearance from the blood during chronic hepatitis C infection. Statins may also serve as potential SARS-CoV-2 main protease inhibitors, thereby contributing to the control of viral infection. In this review, we elaborate on the role of cholesterol level in the process of the coronavirus infection and provide a critical appraisal on the potential of statins in reducing the severity, duration, and complications of COVID-19.<\/jats:p>","DOI":"10.3390\/jcm9061909","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T12:21:46Z","timestamp":1592482906000},"page":"1909","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":118,"title":["Cholesterol in Relation to COVID-19: Should We Care about It?"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1355-6967","authenticated-orcid":false,"given":"Dina","family":"Radenkovic","sequence":"first","affiliation":[{"name":"Guy\u2019s and St Thomas\u2019 Hospital, London SE1 7EH, UK"},{"name":"Faculty of Life Sciences and Medicine, King\u2019s College London, London SE5 9NU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shreya","family":"Chawla","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences and Medicine, King\u2019s College London, London SE5 9NU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Pirro","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, 06123 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8656-1444","authenticated-orcid":false,"given":"Amirhossein","family":"Sahebkar","sequence":"additional","affiliation":[{"name":"Halal Research Center of IRI, FDA, Tehran 314715311, Iran"},{"name":"Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran"},{"name":"Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6690-6874","authenticated-orcid":false,"given":"Maciej","family":"Banach","sequence":"additional","affiliation":[{"name":"Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz (MUL), Zeromskiego 113, 90-549 Lodz, Poland"},{"name":"Polish Mother\u2019s Memorial Hospital Research Institute (PMMHRI), 93-338 Lodz, Poland"},{"name":"Cardiovascular Research Centre, University of Zielona Gora, 65-417 Zielona Gora, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"519","DOI":"10.5114\/aoms.2020.94504","article-title":"Lessons learned from SARS-CoV and MERS-CoV: FDA-approved abelson tyrosine-protein kinase 2 inhibitors may help us combat SARS-CoV-2","volume":"16","author":"Nabavi","year":"2020","journal-title":"Arch. Med. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dolinski, D., Dolinska, B., Zmaczynska-Witek, B., Banach, M., and Kulesza, W. (2020). Unrealistic optimism in the time of coronavirus pandemic: May it help to kill, if so-whom: Disease or the person?. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051464"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"485","DOI":"10.5114\/aoms.2020.94503","article-title":"Lipid-lowering therapy and renin-angiotensin-aldosterone system inhibitors in the era of the COVID-19 pandemic","volume":"16","author":"Katsiki","year":"2020","journal-title":"Arch. Med. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1001\/jama.2020.1585","article-title":"Clinical characteristics of 138 hospitalized patients with 2019 novel Coronavirus-Infected pneumonia in Wuhan, China","volume":"323","author":"Wang","year":"2020","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1001\/jama.2020.2648","article-title":"Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in china: Summary of a report of 72 314 cases from the Chinese center for disease control and prevention","volume":"323","author":"Wu","year":"2020","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Guo, T., Fan, Y., Chen, M., Wu, X., Zhang, L., He, T., Wang, H., Wan, J., Wang, X., and Lu, Z. (2020). Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol.","DOI":"10.1001\/jamacardio.2020.1017"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.atherosclerosis.2015.05.022","article-title":"Statin therapy reduces plasma endothelin-1 concentrations: A meta-analysis of 15 randomized controlled trials","volume":"241","author":"Sahebkar","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1097\/HCO.0000000000000397","article-title":"Statins, haemostatic factors and thrombotic risk","volume":"32","author":"Bianconi","year":"2017","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1160\/th15-08-0620","article-title":"Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group. The impact of statin therapy on plasma levels of von Willebrand factor antigen. Systematic review and meta-analysis of randomised placebo-controlled trials","volume":"115","author":"Sahebkar","year":"2016","journal-title":"Thromb. Haemost."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Madjid, M., Safavi-Naeini, P., Solomon, S.D., and Vardeny, O. (2020). Potential effects of coronaviruses on the cardiovascular system: A review. JAMA Cardiol.","DOI":"10.1001\/jamacardio.2020.1286"},{"key":"ref_11","first-page":"161","article-title":"Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: A possible strategy for reducing SARS-COV-2 infectivity?","volume":"91","author":"Baglivo","year":"2020","journal-title":"Acta Biomed."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3119","DOI":"10.1007\/s00705-018-3967-7","article-title":"Cholesterol is important for the entry process of porcine deltacoronavirus","volume":"163","author":"Jeon","year":"2018","journal-title":"Arch. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.micinf.2006.10.015","article-title":"Lipid rafts play an important role in the early stage of severe acute respiratory syndrome-coronavirus life cycle","volume":"9","author":"Li","year":"2007","journal-title":"Microbes Infect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.bbrc.2008.02.023","article-title":"Lipid rafts are involved in SARS-CoV entry into vero E6 cells","volume":"369","author":"Lu","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9862","DOI":"10.1128\/JVI.79.15.9862-9871.2005","article-title":"Murine coronavirus requires lipid rafts for virus entry and cell-cell fusion but not for virus release","volume":"79","author":"Choi","year":"2005","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Guo, H., Huang, M., Yuan, Q., Wei, Y., Gao, Y., Mao, L., Gu, L., Tan, Y.W., Zhong, Y., and Liu, D. (2017). The important role of lipid raft-mediated attachment in the infection of cultured cells by coronavirus infectious bronchitis virus beaudette strain. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0170123"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/cr.2008.15","article-title":"SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway","volume":"18","author":"Wang","year":"2008","journal-title":"Cell Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10654","DOI":"10.1021\/acs.jpcb.9b08455","article-title":"Membrane cholesterol modulates oligomeric status and peptide-membrane interaction of severe acute respiratory syndrome coronavirus fusion peptide","volume":"123","author":"Meher","year":"2019","journal-title":"J. Phys. Chem. B"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1001\/jamacardio.2016.0433","article-title":"Seasonal influenza infections and cardiovascular disease mortality","volume":"1","author":"Nguyen","year":"2016","journal-title":"JAMA Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wu, C., Postema, P.G., Arbelo, E., Behr, E.R., Bezzina, C.R., Napolitano, C., Robyns, T., Probst, V., Schulze-Bahr, E., and Remme, C.A. (2020). SARS-CoV-2, COVID-19 and inherited arrhythmia syndromes. Heart Rhythm.","DOI":"10.1016\/j.hrthm.2020.03.024"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Shi, S., Qin, M., Shen, B., Cai, Y., Liu, T., Yang, F., Gong, W., Liu, X., Liang, J., and Zhao, Q. (2020). Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol.","DOI":"10.1001\/jamacardio.2020.0950"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Yang, X., Yu, Y., Xu, J., Shu, H., Xia, J., Liu, H., Wu, Y., Zhang, L., Yu, Z., and Fang, M. (2020). Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir. Med.","DOI":"10.1016\/S2213-2600(20)30079-5"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Cismaru, A.C., Laurentiu, C.G., Nabavi, S.F., Berindan-Neagoe, I., Clementi, E., Banach, M., and Nabavi, S.M. (2020). Game of \u201ccrowning\u201d season 8: RAS and reproductive hormones in COVID-19\u2014Can we end this viral series?. Arch. Med. Sci.","DOI":"10.5114\/aoms.2020.96604"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bonow, R.O., Fonarow, G.C., O\u2019Gara, P.T., and Yancy, C.W. (2020). Association of coronavirus disease 2019 (COVID-19) with myocardial injury and mortality. JAMA Cardiol.","DOI":"10.1001\/jamacardio.2020.1105"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s00281-017-0629-x","article-title":"Pathogenic human coronavirus infections: Causes and consequences of cytokine storm and immunopathology","volume":"39","author":"Channappanavar","year":"2017","journal-title":"Semin Immunopathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1111\/j.1365-2362.2009.02153.x","article-title":"SARS-coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS","volume":"39","author":"Oudit","year":"2009","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.2174\/138161212799504803","article-title":"Statins as anti-inflammatory agents in atherogenesis: Molecular mechanisms and lessons from the recent clinical trials","volume":"18","author":"Antonopoulos","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1476-511X-12-47","article-title":"The influence of atorvastatin on parameters of inflammation left ventricular function, hospitalizations and mortality in patients with dilated cardiomyopathy\u20135-year follow-up","volume":"12","author":"Mikhailidis","year":"2013","journal-title":"Lipids Health Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/joim.12406","article-title":"Inflammation and plaque vulnerability","volume":"278","author":"Hansson","year":"2015","journal-title":"J. Intern. Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Banach, M., Serban, C., Sahebkar, A., Mikhailidis, D.P., Ursoniu, S., Ray, K.K., Rysz, J., Toth, P.P., Muntner, P., and Mosteoru, S. (2015). Impact of statin therapy on coronary plaque composition: A systematic review and meta-analysis of virtual histology intravascular ultrasound studies. BMC Med., 13.","DOI":"10.1186\/s12916-015-0459-4"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1001\/jama.291.9.1071","article-title":"Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: A randomized controlled trial","volume":"291","author":"Nissen","year":"2004","journal-title":"JAMA"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Pirro, M., Simental-Mend\u00eda, L.E., Bianconi, V., Watts, G.F., Banach, M., and Sahebkar, A. (2019). Effect of statin therapy on arterial wall inflammation based on 18F-FDG PET\/CT: A systematic review and meta-analysis of interventional studies. J. Clin. Med., 8.","DOI":"10.3390\/jcm8010118"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"237","DOI":"10.5114\/aoms.2020.93253","article-title":"2020 Guidelines of the Polish Society of Laboratory Diagnostics (PSLD) and the Polish Lipid Association (PoLA) on laboratory diagnostics of lipid metabolism disorders","volume":"16","author":"Solnica","year":"2020","journal-title":"Arch. Med. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.phrs.2018.08.014","article-title":"Effect of statins on toll-like receptors: A new insight to pleiotropic effects","volume":"135","author":"Bahrami","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Koushki, K., Shahbaz, S.K., Mashayekhi, K., Sadeghi, M., Zayeri, Z.D., Taba, M.Y., Banach, M., Al-Rasadi, K., Johnston, T.P., and Sahebkar, A. (2020). Anti-inflammatory action of statins in cardiovascular disease: The role of inflammasome and toll-like receptor pathways. Clin. Rev. Allergy Immunol.","DOI":"10.1007\/s12016-020-08791-9"},{"key":"ref_37","first-page":"419","article-title":"Impact of angiotensin-converting enzyme inhibitors and statins on viral pneumonia","volume":"31","author":"Henry","year":"2018","journal-title":"Proc (Bayl. Univ. Med. Cent.)"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"872370","DOI":"10.1155\/2014\/872370","article-title":"Mechanisms of action and efficacy of statins against influenza","volume":"2014","author":"Mehrbod","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1086\/505116","article-title":"Pandemic influenza: A potential role for statins in treatment and prophylaxis","volume":"43","author":"Fedson","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.molcel.2005.04.004","article-title":"Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication","volume":"18","author":"Wang","year":"2005","journal-title":"Mol. Cell."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ali, N., Allam, H., Bader, T., May, R., Basalingappa, K.M., Berry, W.L., Chandrakesan, P., Qu, D., Weygant, N., and Bronze, M.S. (2013). Fluvastatin interferes with hepatitis C virus replication via microtubule bundling and a doublecortin-like kinase-mediated mechanism. PLoS ONE, 8.","DOI":"10.1371\/annotation\/fcc840e2-225c-4d71-920d-a1eab7747e19"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5114\/aoms.2015.49807","article-title":"Statin intolerance\u2014An attempt at a unified definition. Position paper from an international lipid expert panel","volume":"11","author":"Banach","year":"2015","journal-title":"Arch. Med. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.amjmed.2012.04.011","article-title":"Is statin use associated with reduced mortality after pneumonia? A systematic review and meta-analysis","volume":"125","author":"Chopra","year":"2012","journal-title":"Am. J. Med."},{"key":"ref_44","unstructured":"WHO (2020, April 11). Clinical Management of Severe Acute Respiratory Infection When COVID-19 Is Suspected. Available online: https:\/\/www.who.int\/publications-detail\/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.1097\/CCM.0b013e318225742c","article-title":"Effect of pravastatin on the frequency of ventilator-associated pneumonia and on intensive care unit mortality: Open-label, randomized study","volume":"39","author":"Makris","year":"2011","journal-title":"Crit. Care Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1001\/jama.2013.280031","article-title":"Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: A randomized clinical trial","volume":"310","author":"Papazian","year":"2013","journal-title":"JAMA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"795","DOI":"10.2174\/1570161111311050018","article-title":"Rationale of statin therapy in septic patients","volume":"11","author":"Piechota","year":"2013","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Hu, X., Chen, D., Wu, L., He, G., and Ye, W. (2020, February 21). Low serum cholesterol level among patients with COVID-19 infection in Wenzhou, China. Available online: http:\/\/dx.doi.org\/10.2139\/ssrn.3544826.","DOI":"10.2139\/ssrn.3544826"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"490","DOI":"10.5114\/aoms.2020.94655","article-title":"Statins and the COVID-19 main protease: In silico evidence on direct interaction","volume":"16","author":"Reiner","year":"2020","journal-title":"Arch. Med. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"H1084","DOI":"10.1152\/ajpheart.00217.2020","article-title":"COVID-19, ACE2, and the cardiovascular consequences","volume":"318","author":"South","year":"2020","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Nikolic, D., Banach, M., Chianetta, R., Luzzu, L.M., Pantea Stoian, A., Diaconu, C.C., Citarrella, R., Montalto, G., and Rizzo, M. (2020). An overview of statin-induced myopathy and perspectives for the future. Expert Opin. Drug Saf.","DOI":"10.1080\/14740338.2020.1747431"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"104891","DOI":"10.1016\/j.phrs.2020.104891","article-title":"Brief recommendations on the management of adult patients with familial hypercholesterolemia during the COVID-19 pandemic","volume":"158","author":"Banach","year":"2020","journal-title":"Pharmacol. Res."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/6\/1909\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:40:28Z","timestamp":1760175628000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/6\/1909"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,18]]},"references-count":52,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["jcm9061909"],"URL":"https:\/\/doi.org\/10.3390\/jcm9061909","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,18]]}}}