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The Potential Impact of Statins in the Treatment of Patients with COVID-19 Infection

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Coronavirus Therapeutics – Volume I

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1352))

Abstract

  • Introduction: Statins are cholesterol-lowering drugs that also have anti-inflammatory/ immunomodulatory properties, and have been suggested as an adjunct therapy for COVID-19.

  • Methods: To investigate the clinical impact of statins as a potential therapeutic approach in the treatment of cases infected with COVID-19, a systematic search was performed using PubMed and Google Scholar databases. To extend the search results, a set of keywords were used as follows: (“corona virus” OR “Covid-19” OR “SARS-Cov-2” OR “Severe Acute Respiratory Syndrome Coronavirus 2” OR coronavirus) AND (Statins), alongside a manual search in Google Scholar search engine.

  • Results: It has also been suggested that statins could influence the entry of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) into cells by altering the expression of the angiotensin-converting enzyme 2 (ACE2) and CD143 receptors. Statins may be beneficial for COVID-19 patients according to its pleiotropic effects, although, from the clinical aspect, these pleiotropic effects of statins may not be as strong as in preclinical phase on COVID-19. A retrospective study showed favorable effects for statins in SARS-CoV-2 infection.

  • Conclusion: Patients with SARS-CoV-2 infection have a high risk of cardiovascular and thrombotic complications and pleiotropic effects of statins may help manage the COVID-19. There is growing evidence that supports the need for trials of statin treatment in COVID-19 infection.

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References

  • Abeles AM, Pillinger MHJ (2006) Statins as antiinflammatory and immunomodulatory agents: a future in rheumatologic therapy? Arthritis Rheum 54(2):393–407

    Article  CAS  PubMed  Google Scholar 

  • Albert MA, Danielson E, Rifai N, Ridker PM, Jama PIJ (2001) Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA 286(1):64–70

    Article  CAS  PubMed  Google Scholar 

  • Björkhem-Bergman L, Bergman P, Andersson J, Lindh JD (2010) Statin treatment and mortality in bacterial infections – a systematic review and meta-analysis. PLoS One 5(5):e10702

    Article  PubMed Central  PubMed  Google Scholar 

  • Blanc M, Hsieh WY, Robertson KA, Watterson S, Shui G, Lacaze P et al (2011) Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis. PLoS Biol 9(3):e1000598

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Braga VMJ (2002) Cell–cell adhesion and signalling. Curr Opin Cell Biol 14(5):546–556

    Article  CAS  PubMed  Google Scholar 

  • Brousseau ME, Schaefer EJ (2002) Structure and mechanisms of action of HMG-CoA reductase inhibitors. Springer, HMG-CoA Reductase Inhibitors, pp 19–34

    Book  Google Scholar 

  • Canna SW, Behrens EMJ (2012) Making sense of the cytokine storm: a conceptual framework for understanding, diagnosing, and treating hemophagocytic syndromes. Pediatr Clin 59(2):329–344

    Google Scholar 

  • Connors JM, Levy JHJB (2020) COVID-19 and its implications for thrombosis and anticoagulation. J Am Soc Hematol 135(23):2033–2040

    CAS  Google Scholar 

  • DeDiego ML, Nieto-Torres JL, Regla-Nava JA, Jimenez-Guardeño JM, Fernandez-Delgado R, Fett C et al (2014) Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J Virol 88(2):913–924

    Article  PubMed Central  PubMed  Google Scholar 

  • Devaux CA, Rolain J-M, Raoult D (2020) ACE2 receptor polymorphism: susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome. J Microbiol Immunol Infect 53(3):425–435

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dong B, Zhang C, Feng JB, Zhao YX, Li SY, Yang YP et al (2008) Overexpression of ACE2 enhances plaque stability in a rabbit model of atherosclerosis. Arterioscler Thromb Vasc Biol 28(7):1270–1276

    Article  CAS  PubMed  Google Scholar 

  • Elahi S, Weiss RH, Merani S (2016) Atorvastatin restricts HIV replication in CD4+ T cells by upregulation of p21. AIDS (London, England) 30(2):171–183

    Article  CAS  Google Scholar 

  • Elnaem MH, Mohamed MHN, Huri HZ, Azarisman SM, Elkalmi RM (2017) Statin therapy prescribing for patients with type 2 diabetes mellitus: a review of current evidence and challenges. J Pharm Bioallied Sci 9(2):80–87

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Eto M, Kozai T, Cosentino F, Joch H, Lüscher TFJ (2002) Statin prevents tissue factor expression in human endothelial cells: role of Rho/Rho-kinase and Akt pathways. Circulation. 105(15):1756–1759

    Article  CAS  PubMed  Google Scholar 

  • Gallelli L, Falcone D, Scaramuzzino M, Pelaia G, D’Agostino B, Mesuraca M et al (2014) Effects of simvastatin on cell viability and proinflammatory pathways in lung adenocarcinoma cells exposed to hydrogen peroxide. BMC Pharm Toxicol 15:67

    Article  Google Scholar 

  • Gao S, Zhang ZM, Shen ZL, Gao K, Chang L, Guo Y et al (2016) Atorvastatin activates autophagy and promotes neurological function recovery after spinal cord injury. Neural Regen Res 11(6):977–982

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ghittoni R, Patrussi L, Pirozzi K, Pellegrini M, Lazzerini PE, Capecchi PL et al (2005) Simvastatin inhibits T-cell activation by selectively impairing the function of Ras superfamily GTPases. FASEB J 19(6):1–24

    Article  Google Scholar 

  • Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y et al (2020) Structure of M(pro) from SARS-CoV-2 and discovery of its inhibitors. Nature 582(7811):289–293

    Article  CAS  PubMed  Google Scholar 

  • Klok F, Kruip M, Van der Meer N, Arbous M, Gommers D, Kant K et al (2020) Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res

    Google Scholar 

  • Kowalski J, Okopień B, Madej A, Zieliński M, Belowski D, Kalina Z et al (2003) Effects of atorvastatin, simvastatin, and fenofibrate therapy on monocyte chemoattractant protein-1 secretion in patients with hyperlipidemia. Eur J Clin Pharmacol 59(3):189–193

    Article  CAS  PubMed  Google Scholar 

  • Kumar V, Dhanjal JK, Bhargava P, Kaul A, Wang J, Zhang H et al (2020) Withanone and Withaferin-a are predicted to interact with transmembrane protease serine 2 (TMPRSS2) and block entry of SARS-CoV-2 into cells. J Biomol Struct Dyn:1–13

    Google Scholar 

  • Kwak B, Mulhaupt F, Myit S, Mach FJ (2000) Statins as a newly recognized type of immunomodulator. Nat Med 6(12):1399–1402

    Article  CAS  PubMed  Google Scholar 

  • Lange PT, Darrah EJ, Vonderhaar EP, Mboko WP, Rekow MM, Patel SB et al (2016) Type I interferon counteracts antiviral effects of statins in the context of Gammaherpesvirus infection. J Virol 90(7):3342–3354

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lange C, Wolf J, Auw-Haedrich C, Schlecht A, Boneva S, Lapp T et al (2020) Expression of the COVID-19 receptor ACE2 in the human conjunctiva. J Med Virol 92(10):2081–2086

    Article  CAS  PubMed  Google Scholar 

  • Lee KCH, Sewa DW, Phua GC (2020) Potential role of statins in COVID-19. Int J Infect Dis IJID Off Publ Int Soc Infect Dis 96:615–617

    CAS  Google Scholar 

  • Li Y-H, Wang Q-X, Zhou J-W, Chu X-M, Man Y-L, Liu P et al (2013) Effects of rosuvastatin on expression of angiotensin-converting enzyme 2 after vascular balloon injury in rats. J Geriat Cardiol 10(2):151

    CAS  Google Scholar 

  • Liang X, Yang LX, Guo R, Shi Y, Hou X, Yang Z et al (2017) Atorvastatin attenuates plaque vulnerability by downregulation of EMMPRIN expression via COX-2/PGE2 pathway. Exp Ther Med 13(3):835–844

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lin SJ, Chen YH, Lin FY, Hsieh LY, Wang SH, Lin CY et al (2007) Pravastatin induces thrombomodulin expression in TNFα-treated human aortic endothelial cells by inhibiting Rac1 and Cdc42 translocation and activity. J Cell Biochem 101(3):642–653

    Article  CAS  PubMed  Google Scholar 

  • Mason RJ (2020) Pathogenesis of COVID-19 from a cell biology perspective. Eur Res J 55(4)

    Google Scholar 

  • Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ et al (2020) COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 395(10229):1033

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Min JJ, Shin B-S, Lee J-H, Jeon Y, Ryu DK, Kim S et al (2018) Effects of pravastatin on type 1 diabetic rat heart with or without blood glycemic control. J Diabetes Res 2018

    Google Scholar 

  • Okopień B, Krysiak R, Kowalski J, Madej A, Belowski D, Zieliński M et al (2004) The effect of statins and fibrates on interferon-γ and interleukin-2 release in patients with primary type II dyslipidemia. Atherosclerosis 176(2):327–335

    Article  PubMed  Google Scholar 

  • Pasceri V, Chang J, Willerson JT, Yeh ETJ (2001) Modulation of C-reactive protein–mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation 103(21):2531–2534

    Article  CAS  PubMed  Google Scholar 

  • Reiner Ž, Hatamipour M, Banach M, Pirro M, Al-Rasadi K, Jamialahmadi T et al (2020) Statins and the COVID-19 main protease: in silico evidence on direct interaction. Arch Med Sci 16(3):490–496

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rezaie-Majd A, Maca T, Bucek RA, Valent P, Müller MR, Husslein P et al (2002) Simvastatin reduces expression of cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 in circulating monocytes from hypercholesterolemic patients. Arterioscler Thromb Vasc Biol 22(7):1194–1199

    Article  PubMed  Google Scholar 

  • Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ et al (2009) Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet 373(9670):1175–1182

    Article  CAS  PubMed  Google Scholar 

  • Romano M, Diomede L, Sironi M, Massimiliano L, Sottocorno M, Polentarutti N et al (2000) Inhibition of monocyte chemotactic protein-1 synthesis by statins. Lab Investig 80(7):1095–1100

    Article  CAS  PubMed  Google Scholar 

  • Sahebkar A, Serban C, Mikhailidis DP, Undas A, Lip GY, Muntner P et al (2015) Association between statin use and plasma D-dimer levels. Thrombosis Haemostasis 114(09):546–557

    Article  PubMed  Google Scholar 

  • Sasidhar MV, Chevooru SK, Eickelberg O, Hartung H-P, OJP N (2017) Downregulation of monocytic differentiation via modulation of CD147 by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Plos ONE 12(12):e0189701

    Article  PubMed Central  PubMed  Google Scholar 

  • Sheahan T, Morrison TE, Funkhouser W, Uematsu S, Akira S, Baric RS et al (2008) MyD88 is required for protection from lethal infection with a mouse-adapted SARS-CoV. PLoS Pathog 4(12):e1000240

    Article  PubMed Central  PubMed  Google Scholar 

  • Totura AL, Whitmore A, Agnihothram S, Schäfer A, Katze MG, Heise MT et al (2015) Toll-like receptor 3 signaling via TRIF contributes to a protective innate immune response to severe acute respiratory syndrome coronavirus infection. mBio 6(3):e00638-15

    Article  PubMed Central  PubMed  Google Scholar 

  • Ulrich H, Pillat MM (2020) CD147 as a target for COVID-19 treatment: suggested effects of azithromycin and stem cell engagement. Stem Cell Rev Rep 16(3):434–440

    Article  CAS  PubMed  Google Scholar 

  • van der Lee M, Sankatsing R, Schippers E, Vogel M, Fätkenheuer G, van der Ven A et al (2007) Pharmacokinetics and pharmacodynamics of combined use of lopinavir/ritonavir and rosuvastatin in HIV-infected patients. Antivir Ther 12(7):1127–1132

    Article  PubMed  Google Scholar 

  • Wæhre T, Yndestad A, Smith C, Haug T, Tunheim SH, Gullestad L et al (2004) Increased expression of interleukin-1 in coronary artery disease with downregulatory effects of HMG-CoA reductase inhibitors. Circulation 109(16):1966–1972

    Article  PubMed  Google Scholar 

  • Ward NC, Watts GF, Eckel RH (2019) Statin toxicity. Circul Res 124(2):328–350

    Article  CAS  Google Scholar 

  • Weitz-Schmidt G, Welzenbach K, Brinkmann V, Kamata T, Kallen J, Bruns C et al (2001) Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med 7(6):687–692

    Article  CAS  PubMed  Google Scholar 

  • Xu H, Liu P, Liang L, Danesh FR, Yang X, Ye Y et al (2006) RhoA-mediated, tumor necrosis factor α–induced activation of NF-κB in rheumatoid synoviocytes: Inhibitory effect of simvastatin. Arthritis Rheum 54(11):3441–3451

    Article  CAS  PubMed  Google Scholar 

  • Yang Z, Su Z, DeWitt JP, Xie L, Chen Y, Li X et al (2017) Fluvastatin prevents lung adenocarcinoma bone metastasis by triggering autophagy. EBioMedicine 19:49–59

    Article  PubMed Central  PubMed  Google Scholar 

  • Yuan S (2015) Statins may decrease the fatality rate of middle east respiratory syndrome infection. mBio 6(4):e01120

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yuan X, Deng Y, Guo X, Shang J, Zhu D, Liu H (2014) Atorvastatin attenuates myocardial remodeling induced by chronic intermittent hypoxia in rats: partly involvement of TLR-4/MYD88 pathway. Biochem Biophys Res Commun 446(1):292–297

    Article  CAS  PubMed  Google Scholar 

  • Yuki K, Fujiogi M, Koutsogiannaki S (2020) COVID-19 pathophysiology: a review. Clin Immunol (Orlando, Fla) 215:108427

    Article  CAS  Google Scholar 

  • Zeiser R (2018) Immune modulatory effects of statins. Immunology 154(1):69–75

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang X-J, Qin J-J, Cheng X, Shen L, Zhao Y-C, Yuan Y et al (2020) In-hospital use of statins is associated with a reduced risk of mortality among individuals with COVID-19. Cell Metab

    Google Scholar 

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Conflict of Interest

The authors have no conflict of interest to disclose.

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Authors and Affiliations

  1. Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Reza Jafarzadeh Esfehani

  2. Atherosclerosis Prevention Research Center, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohammad Vojdanparast

  3. Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Saman Soleimanpour

  4. Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Saman Soleimanpour

  5. Student Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Saman Soleimanpour & Amir Avan

  6. Metabolic syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Saman Soleimanpour & Amir Avan

  7. Brighton & Sussex Medical School, Division of Medical Education, Sussex, UK

    Gordon A. Ferns

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  1. Reza Jafarzadeh Esfehani
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  2. Mohammad Vojdanparast
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  3. Saman Soleimanpour
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  4. Gordon A. Ferns
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  5. Amir Avan
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Correspondence to Reza Jafarzadeh Esfehani or Amir Avan .

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Editors and Affiliations

  1. President & CEO, NampEVA BioTherapeutics LLC, Dover, DE, USA

    Alexzander A. A. Asea

  2. Department of Medicine and Precision Therapeutics Proteogenomics Diagnostic Center Eleanor N. Dana Cancer Center, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

    Punit Kaur

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Esfehani, R.J., Vojdanparast, M., Soleimanpour, S., Ferns, G.A., Avan, A. (2021). The Potential Impact of Statins in the Treatment of Patients with COVID-19 Infection. In: Asea, A.A.A., Kaur, P. (eds) Coronavirus Therapeutics – Volume I. Advances in Experimental Medicine and Biology, vol 1352. Springer, Cham. https://doi.org/10.1007/978-3-030-85109-5_9

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