The Effects of Statins on Respiratory Symptoms and Pulmonary Fibrosis in COVID-19 Patients with Diabetes Mellitus: A Longitudinal Multicenter Study

Overview

Journal Arch Immunol Ther Exp (Warsz)

Publisher Sciendo

Specialty Allergy & Immunology

Date 2023 Feb 28

PMID 36853269

Authors

Mohammadamin Sadeghdoust

Farnaz Aligolighasemabadi

Tania Dehesh

Nima Taefehshokr

Adel Sadeghdoust

Katarzyna Kotfis

Amirhossein Hashemiattar

Amir Ravandi

Neda Aligolighasemabadi

Omid Vakili

Beniamin Grabarek

Rafal Staszkiewicz

Marek J Los

Pooneh Mokarram

Saeid Ghavami

Affiliations

Soon will be listed here.

Abstract

The aim of this prospective cohort study was to explore the effect of statins on long-term respiratory symptoms and pulmonary fibrosis in coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM). Patients were recruited from three tertiary hospitals, categorized into Statin or Non-statin groups, and assessed on days 0, 28, and 90 after symptoms onset to record the duration of symptoms. Pulmonary fibrosis was scored at baseline and follow-up time points by high-resolution computed tomography scans. Each group comprised 176 patients after propensity score matching. Data analysis revealed that the odds of having cough and dyspnea were significantly higher in the Non-statin group compared to the Statin group during the follow-up period. Overall, there was no significant difference in the change in pulmonary fibrosis score between groups. However, Non-statin patients with > 5 years of DM were more likely to exhibit a significantly higher fibrosis score during the follow-up period as compared to their peers in the Statin group. Our results suggest that the use of statins is associated with a lower risk of developing chronic cough and dyspnea in diabetic patients with COVID-19, and may reduce pulmonary fibrosis associated with COVID-19 in patients with long-term (> 5 years) DM.

Citing Articles

The protective effect and experimental research progress of pleotropic statins in intervertebral disc degeneration.

Zhang X, Li S, Liu X, Ma Z, Zhang Q, Zhang Y J Orthop Surg Res. 2025; 20(1):122.

PMID: 39891158 PMC: 11783947. DOI: 10.1186/s13018-025-05487-8.

Cholesterol and Cholesterol-Lowering Medications in COVID-19-An Unresolved Matter.

Grewal T, Nguyen M, Buechler C Int J Mol Sci. 2024; 25(19).

PMID: 39408818 PMC: 11477656. DOI: 10.3390/ijms251910489.

The Significance of Endothelial Dysfunction in Long COVID-19 for the Possible Future Pandemic of Chronic Kidney Disease and Cardiovascular Disease.

Yanai H, Adachi H, Hakoshima M, Katsuyama H, Sako A Biomolecules. 2024; 14(8).

PMID: 39199353 PMC: 11352301. DOI: 10.3390/biom14080965.

Strengthening pharmacotherapy research for COVID-19-induced pulmonary fibrosis.

Liu Y, Zhang J, Wu J, Guo W, Tang F World J Clin Cases. 2024; 12(5):875-879.

PMID: 38414600 PMC: 10895630. DOI: 10.12998/wjcc.v12.i5.875.

Lipid rafts disruption by statins negatively impacts the interaction between SARS-CoV-2 S1 subunit and ACE2 in intestinal epithelial cells.

El Khoury M, Naim H Front Microbiol. 2024; 14:1335458.

PMID: 38260879 PMC: 10800905. DOI: 10.3389/fmicb.2023.1335458.

References

Adhyaru B, Jacobson T . Safety and efficacy of statin therapy. Nat Rev Cardiol. 2018; 15(12):757-769. DOI: 10.1038/s41569-018-0098-5. View

Ahmadi M, Amiri S, Pecic S, Machaj F, Rosik J, Los M . Pleiotropic effects of statins: A focus on cancer. Biochim Biophys Acta Mol Basis Dis. 2020; 1866(12):165968. DOI: 10.1016/j.bbadis.2020.165968. View

Alizadeh J, Zeki A, Mirzaei N, Tewary S, Moghadam A, Glogowska A . Mevalonate Cascade Inhibition by Simvastatin Induces the Intrinsic Apoptosis Pathway via Depletion of Isoprenoids in Tumor Cells. Sci Rep. 2017; 7:44841. PMC: 5366866. DOI: 10.1038/srep44841. View

Alizadeh J, Glogowska A, Thliveris J, Kalantari F, Shojaei S, Hombach-Klonisch S . Autophagy modulates transforming growth factor beta 1 induced epithelial to mesenchymal transition in non-small cell lung cancer cells. Biochim Biophys Acta Mol Cell Res. 2018; 1865(5):749-768. DOI: 10.1016/j.bbamcr.2018.02.007. View

Araya J, Kojima J, Takasaka N, Ito S, Fujii S, Hara H . Insufficient autophagy in idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2012; 304(1):L56-69. DOI: 10.1152/ajplung.00213.2012. View

Camiciottoli G, Orlandi I, Bartolucci M, Meoni E, Nacci F, Diciotti S . Lung CT densitometry in systemic sclerosis: correlation with lung function, exercise testing, and quality of life. Chest. 2007; 131(3):672-681. DOI: 10.1378/chest.06-1401. View

Cariou B, Goronflot T, Rimbert A, Boullu S, Le May C, Moulin P . Routine use of statins and increased COVID-19 related mortality in inpatients with type 2 diabetes: Results from the CORONADO study. Diabetes Metab. 2020; 47(2):101202. PMC: 7572108. DOI: 10.1016/j.diabet.2020.10.001. View

Davoodi L, Jafarpour H, Oladi Z, Zakariaei Z, Tabarestani M, Ahmadi B . Atorvastatin therapy in COVID-19 adult inpatients: A double-blind, randomized controlled trial. Int J Cardiol Heart Vasc. 2021; 36:100875. PMC: 8437805. DOI: 10.1016/j.ijcha.2021.100875. View

Drozdzal S, Rosik J, Lechowicz K, Machaj F, Szostak B, Przybycinski J . An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment. Drug Resist Updat. 2022; 59:100794. PMC: 8654464. DOI: 10.1016/j.drup.2021.100794. View

10.

Elahi S, Weiss R, Merani S . Atorvastatin restricts HIV replication in CD4+ T cells by upregulation of p21. AIDS. 2015; 30(2):171-83. DOI: 10.1097/QAD.0000000000000917. View

11.

Emami A, Shojaei S, da Silva Rosa S, Aghaei M, Samiei E, Vosoughi A . Mechanisms of simvastatin myotoxicity: The role of autophagy flux inhibition. Eur J Pharmacol. 2019; 862:172616. DOI: 10.1016/j.ejphar.2019.172616. View

12.

Gawish R, Starkl P, Pimenov L, Hladik A, Lakovits K, Oberndorfer F . ACE2 is the critical in vivo receptor for SARS-CoV-2 in a novel COVID-19 mouse model with TNF- and IFNγ-driven immunopathology. Elife. 2022; 11. PMC: 8776253. DOI: 10.7554/eLife.74623. View

13.

George P, Wells A, Gisli Jenkins R . Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy. Lancet Respir Med. 2020; 8(8):807-815. PMC: 7228727. DOI: 10.1016/S2213-2600(20)30225-3. View

14.

Ghavami S, Mutawe M, Schaafsma D, Yeganeh B, Unruh H, Klonisch T . Geranylgeranyl transferase 1 modulates autophagy and apoptosis in human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2011; 302(4):L420-8. DOI: 10.1152/ajplung.00312.2011. View

15.

Ghavami S, Sharma P, Yeganeh B, Ojo O, Jha A, Mutawe M . Airway mesenchymal cell death by mevalonate cascade inhibition: integration of autophagy, unfolded protein response and apoptosis focusing on Bcl2 family proteins. Biochim Biophys Acta. 2014; 1843(7):1259-71. DOI: 10.1016/j.bbamcr.2014.03.006. View

16.

Ghavami S, Cunnington R, Gupta S, Yeganeh B, Filomeno K, Freed D . Autophagy is a regulator of TGF-β1-induced fibrogenesis in primary human atrial myofibroblasts. Cell Death Dis. 2015; 6:e1696. PMC: 4385916. DOI: 10.1038/cddis.2015.36. View

17.

Ghavami S, Yeganeh B, Zeki A, Shojaei S, Kenyon N, Ott S . Autophagy and the unfolded protein response promote profibrotic effects of TGF-β in human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2017; 314(3):L493-L504. PMC: 5900356. DOI: 10.1152/ajplung.00372.2017. View

18.

Gower T, Graham B . Antiviral activity of lovastatin against respiratory syncytial virus in vivo and in vitro. Antimicrob Agents Chemother. 2001; 45(4):1231-7. PMC: 90448. DOI: 10.1128/AAC.45.4.1231-1237.2001. View

19.

Gu W, Cui R, Ding T, Li X, Peng J, Xu W . Simvastatin alleviates airway inflammation and remodelling through up-regulation of autophagy in mouse models of asthma. Respirology. 2016; 22(3):533-541. DOI: 10.1111/resp.12926. View

20.

Guo W, Li M, Dong Y, Zhou H, Zhang Z, Tian C . Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev. 2020; 36(7):e3319. PMC: 7228407. DOI: 10.1002/dmrr.3319. View