Effect of Statin Treatment on COVID-19 Patients’ Outcomes: A Randomized Double-blind Controlled Clinical Trial

authors:

avatar Rozita Behadori 1 , * , avatar Samira Dodangeh 2 , avatar Azam Nabavi 1 , avatar Abbas Allami ORCID 1

Department of Infectious Diseases, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Children Growth Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran.
Journal of Inflammatory Diseases: Vol.26, issue 2; 89-98
article type: issue_documents_importer

how to cite: Behadori R, Dodangeh S, Nabavi A, Allami A. Effect of Statin Treatment on COVID-19 Patients’ Outcomes: A Randomized Double-blind Controlled Clinical Trial. J Inflamm Dis. 2022;26(2):e156313. 

Abstract

Background: Statins may be protective against viral infection and have been suggested for the treatment of coronavirus disease 2019 (COVID-19).  Objective: In this study, we aimed to evaluate the effect of atorvastatin on COVID-19 patients. Methods: Our study is a randomized double-blind controlled clinical trial that constitutes a population of COVID-19 patients admitted to Bu-Ali Sina Hospital in Qazvin, Iran, from May to August 2021. For the intervention and control groups, in addition to the national standard treatment, atorvastatin 40 mg tablet and placebo were daily administered for 7 days, respectively. A questionnaire including demographic characteristics, history of underlying diseases, vital signs, laboratory and imaging results, and outcome (alive, died) was completed on the first, third, and fifth days of hospitalization. Finally, the obtained data were analyzed by SPSS software, version 25. Findings: One hundred five patients with COVID-19 (62 females and 43 males, mean age 69 years) were studied. On days 3 and 5 after the intervention, no significant difference was observed between the groups in terms of vital signs, laboratory findings, hospitalization time, and need for intensive care unit hospitalization. However, 5.7% of patients in the atorvastatin group and 0% of patients in the control group died (P=0.243). Among the studied variables, C-reactive protein (P=0.227 vs P=0.002), blood urea nitrogen (P=0.055 vs P<0.001), and creatinine (P=0.598 vs P=0.013) decreased significantly in the statin group (no control group during days 0-5). Conclusion: There was no evidence about the harm and benefits of statin treatment during COVID-19 hospitalization.

References

  • 1.

    Wu Z, McGoogan JM. 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. JAMA. 2020;323(13):1239-42. [DOI: https://doi.org/10.1001/jama.2020.2648] PMID: 32091533;.

  • 2.

    Ahmed M, Farag A, Boys IN, et al. Identification of atovaquone, ouabain and mebendazole as FDA approved drugs Tar-geting SARS-CoV-2 (Sep 06, 2021 version 6). 2021. [DOI: https://doi.org/10.33774/chemrxiv-2021-b3fv1-v7].

  • 3.

    Oesterle A, Laufs U, Liao JK. Pleiotropic effects of statins on the cardiovascular system. Circ Res. 2017;120(1):229-43. PMID: 28057795; [DOI: https://doi.org/10.1161/CIRCRESAHA.116.308537].

  • 4.

    Zeiser R. Immune modulatory effects of statins. Immunology. 2018;154(1):69-75. PMID: 29392731; [DOI: https://doi.org/10.1111/imm.12902].

  • 5.

    Van de Garde EM, Hak E, Souverein PC, et al. Statin treatment and reduced risk of pneumonia in patients with diabetes. Thorax. 2006;61(11):957-61. [DOI: https://doi.org/10.1136/thx.2006.062885] PMID: 16809409.

  • 6.

    Khurana V, Bejjanki HR, Caldito G, Owens MW. Statins reduce the risk of lung cancer in humans: a large case-control study of US veterans. Chest. 2007;131(5):1282-8. [DOI: https://doi.org/10.1378/chest.06-0931] PMID: 17494779;.

  • 7.

    Jacobson JR, Barnard JW, Grigoryev DN, et al. Simvastatin attenuates vascular leak and inflammation in murine inflammatory lung injury. Am J Physiol Lung Cell Mol Physiol.. 2005;288(6):L1026-L32. [DOI: https://doi.org/10.1152/ajplung.00354.2004] PMID: 15665042;.

  • 8.

    Golomb BA, Dimsdale JE, White HL, Ritchie JB, Criqui MH. Reduction in blood pressure with statins: results from the UCSD Statin Study, a randomized trial. Arch Intern Med.2008;168(7):721-7. [DOI: https://doi.org/10.1001/archinte.168.7.721] PMID: 18413554.

  • 9.

    Zeenny RM, Mansour H, Kabbara WK, Chamoun N, Audi M, Yared Y, Salameh P. Effects of statins on clinical outcomes in hospitalized patients with community-acquired pneumonia. Journal of International Medical Research. 2020 Aug;48(8):0300060520938586.

  • 10.

    Feldman C. The role of statins in respiratory diseases. Clin Pulm Med.. 2009;16(2):95-100. [DOI: https://doi.org/10.1097/CPM.0b013e31819b3a41].

  • 11.

    Parihar SP, Guler R, Brombacher F. Statins: a viable candidate for host-directed therapy against infectious diseases. Nat Rev Immunol. 2019;19(2): 104-17. [DOI: https://doi.org/10.1038/s41577-018-0094-3] PMID: 30487528.

  • 12.

    Aronov D. [Pleiotropic effects of statins]. Kardiologiia. 2008;48(8):60-8. Russian. PMID: 18789012.

  • 13.

    Najjar A, Daei MM, Dodangeh S, Allami. A Prediction of the risk factors for Covid-19 infection in progression to Severe Disease in Bu-Ali Sina Hospital, Qazvin, Iran. Pathobiol Res. 2021;24(1):55-61. Available from: https://mjms.modares.ac.ir/article-30-52671-en.html.

  • 14.

    Najjar A, Allami A, Dodangeh S, Daei MM. The effect of coronavirus infection on QT and QTc intervals of hospitalized patients in Qazvin, Iran. Ann Data Sci. 2022 Aug 4:1-2. [DOI: https://doi.org/10.1007/s40745-022-00425-5].

  • 15.

    Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The lancet. 2020;395(10229):1054-62. [DOI: https://doi.org/10.1016/S0140-6736(20)30566-3] PMID: 32171076.

  • 16.

    Inciardi RM, Lupi L, Zaccone G, et al. Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19). JAMA cardiol. 2020;5(7):819-24. [DOI: https://doi.org/10.1001/jamacardio.2020.1096] PMID: 32219357.

  • 17.

    Whitlock R, Healey JS, Connolly SJ, et al. Predictors of early and late stroke following cardiac surgery. CMAJ. 2014;186(12):905-11. [DOI: https://doi.org/10.1503/cmaj.131214] PMID: 25047983.

  • 18.

    Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirusinfected pneumonia in Wuhan, China. JAMA. 2020; 323 (11): 1061-9. [DOI: https://doi.org/10.1001/jama.2020.1585] PMID: 32031570;.

  • 19.

    Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet. 2020;395(10223):497-506. [DOI: https://doi.org/10.1016/S0140-6736(20)30183-5] PMID: 31986264.

  • 20.

    Shi S, Qin M, Shen B, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA cardiol. 2020;5(7):802-10. [DOI: https://doi.org/10.1001/jamacardio.2020.0950] PMID: 32211816;.

  • 21.

    Shi S, Qin M, Cai Y, et al. Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019. Eur Heart J. 2020;41(22):2070-9. [DOI: https://doi.org/10.1093/eurheartj/ehaa408] PMID: 32391877.

  • 22.

    Guan W-j, Ni Z-y, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-20. [DOI: https://doi.org/10.1056/NEJMoa2002032].

  • 23.

    Zheng Y-Y, Ma Y-T, Zhang J-Y, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020;17(5):259-60. [DOI: https://doi.org/10.1038/s41569-020-0360-5].

  • 24.

    Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis.2020;94:91-5. [DOI: https://doi.org/10.1016/j.ijid.2020.03.017] PMID: 32173574.

  • 25.

    Li B, Yang J, Zhao F, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. 2020; 109 (5): 531-8. [DOI: https://doi.org/10.1007/s00392-020-01626-9] PMID: 32161990.

  • 26.

    Kuo FY, Huang WC, Tang PL, et al. Impact of statin on long-term outcome among patients with end-stage renal disease with acute myocardial infarction (AMI): a nationwide casecontrol study. Postgrad Med J. 2021; 97(1147):299-305. [DOI: https://doi.org/10.1136/postgradmedj-2019-137292] PMID: 33452152.

  • 27.

    Reiner , Hatamipour M, Banach M, et al. Statins and the COVID-19 main protease: in silico evidence on direct interaction. Arch Med Sci. 2020;16(3):490. [DOI: https://doi.org/10.5114/aoms.2020.94655] PMID: 32399094.

  • 28.

    Zapatero-Belinchon FJ, Moeller R, Lasswitz L, et al. Fluvastatin mitigates SARS-CoV-2 infection in human lung cells. medRxiv 2020.07.13.20152272; COVID-19 SARS-CoV-2 preprints, [DOI: https://doi.org/10.1101/2020.07.13.20152272].

  • 29.

    Virani SS. Is there a role for statin therapy in acute viral infections. Cardiology Magazine. Washington, DC: American College of Cardiology; 2020. https://www.acc.org/latest-in-cardiology/articles/2020/03/18/15/09/is-there-a-role-for-statin-therapy-in-acute-viral-infections-covid-19.

  • 30.

    Vahedian-Azimi A, Mohammadi SM, Banach M, et al. Improved COVID-19 Outcomes following Statin Therapy: An Updated Systematic Review and Meta-analysis. Biomed Res Int. 2021 Sep 23;2021:1901772. eCollection 2021. [DOI: https://doi.org/10.1155/2021/1901772] PMID: 34568488.

  • 31.

    De Spiegeleer A, Bronselaer A, Teo JT, et al. The effects of ARBs, ACEis, and statins on clinical outcomes of COVID-19 infection among nursing home residents. J Am Med Dir Assoc. 2020;21(7):909-14. e2. [DOI: https://doi.org/10.1016/j.jamda.2020.06.018] PMID: 32674818.

  • 32.

    Hariyanto TI, Kurniawan A. Statin therapy did not improve the in-hospital outcome of coronavirus disease 2019 (COVID-19) infection. Diabetes Metab Syndr 2020;14(6):1613-5. [DOI: https://doi.org/10.1016/j.dsx.2020.08.023] PMID: 32882643.

  • 33.

    Grasselli G, Greco M, Zanella A, et al. Risk factors associated with mortality among patients with COVID-19 in intensive care units in Lombardy, Italy. JAMA internal medicine. 2020;180(10):1345-55. [DOI: https://doi.org/10.1001/jamainternmed.2020.3539 PMID: 32667669.

  • 34.

    Ghafoori M, Saadati H, Taghavi M, Azimian A, Alesheikh P, Mohajerzadeh MS, Behnamfar M, Pakzad M, Rameshrad M. Survival of the hospitalized patients with COVID?19 receiving atorvastatin: A randomized clinical trial. J Med Virol. 2022 Jul; 94(7): 31608.

  • 35.

    Jones BE, Jones J, Bewick T, et al. CURB-65 pneumonia severity assessment adapted for electronic decision support. Chest. 2011;140(1):156-163. [DOI: https://doi.org/10.1378/chest.10-1296] PMID: 21163875.

  • 36.

    Sharafi S, Allami A. Efficacy of zinc sulphate on in-hospital outcome of community-acquired pneumonia in people aged 50 years and over. Int J Tuberc Lung Dis. 2016;20(5):685-688. [DOI: https://doi.org/10.5588/ijtld.15.0653] PMID: 27084825.

  • 37.

    Hayes AF. Partial, conditional, and moderated moderated mediation: Quantification, inference, and interpretation. Commun Monogr. 2018;85(1):4-40.

  • 38.

    Vandermeer ML, Thomas AR, Kamimoto L, et al. Association between use of statins and mortality among patients hospitalized with laboratory-confirmed influenza virus infections: a multistate study. J Infect Dis. 2012;205(1):13-9. [DOI: https://doi.org/10.1093/infdis/jir695] PMID: 22170954.

  • 39.

    Fleming D, Verlander N, Elliot A, et al. An assessment of the effect of statin use on the incidence of acute respiratory infections in England during winters 19981999 to 2005-2006. Epidemiol Infect. 2010;138(9):1281-8. [DOI: https://doi.org/10.1017/S0950268810000105] PMID: 20109259.

  • 40.

    Papazian L, Roch A, Charles P-E, et al. Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: a randomized clinical trial. JAMA. 2013;310(16):1692-700. [DOI: https://doi.org/10.1001/jama.2013.280031] PMID: 24108510.

  • 41.

    Yuan S. Statins may decrease the fatality rate of Middle East respiratory syndrome infection. MBio. 2015;6(4):e01120-15. [DOI: https://doi.org/10.1128/mBio.01120-15] PMID: 26265720.

  • 42.

    Brett SJ, Myles P, Lim WS, et al. Pre-admission statin use and in-hospital severity of 2009 pandemic influenza A (H1N1) disease. PLoS One. 2011;6(4):e18120. PMID: 21541017; [DOI: https://doi.org/10.1371/journal.pone.0018120].

  • 43.

    Zhang X-J, Qin J-J, Cheng X, et al. In-hospital use of statins is associated with a reduced risk of mortality among individuals with COVID-19. Cell Metab.. 2020;32(2):176-87. e4. [DOI: https://doi.org/10.1016/j.cmet.2020.06.015] PMID: 32592657.

  • 44.

    Kow CS, Hasan SS. The association between the use of statins and clinical outcomes in patients with COVID-19: a systematic review and meta-analysis. Am J Cardiovasc Drugs. 2022, 22, 16781.

  • 45.

    Ghafoori M, Saadati H, Taghavi M, Azimian A, Alesheikh P, Mohajerzadeh MS, Behnamfar M, Pakzad M, Rameshrad M. Survival of the hospitalized patients with COVID?19 receiving atorvastatin: A randomized clinical trial. J Med Virol. 2022 Jul; 94(7): 31608. [DOI: https://doi.org/10.1002/jmv.27710] PMID: 35274326.

  • 46.

    Hejazi S, Mircheraghi F, Elyasi S, Davoodian N, Salarbashi D, Majd HM. Atorvastatin efficacy in the management of mild to moderate hospitalized COVID-19: a pilot randomized triple-blind placebo-controlled clinical trial. Recent Advances in Anti-infective Drug Discovery. 2022, 17 [DOI: https://doi.org/10.2174/2772434417666220902153823] PMID: 36056874##.