The Effects of Statins on Respiratory Symptoms and Pulmonary Fibrosis in COVID-19 Patients with Diabetes Mellitus: A Longitudinal Multicenter Study.
COVID-19
Diabetes mellitus
Post-acute COVID-19 syndrome
Pulmonary fibrosis
Statins
Journal
Archivum immunologiae et therapiae experimentalis
ISSN: 1661-4917
Titre abrégé: Arch Immunol Ther Exp (Warsz)
Pays: Switzerland
ID NLM: 0114365
Informations de publication
Date de publication:
28 Feb 2023
28 Feb 2023
Historique:
received:
29
09
2022
accepted:
14
12
2022
entrez:
28
2
2023
pubmed:
1
3
2023
medline:
3
3
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36853269
doi: 10.1007/s00005-023-00672-1
pii: 10.1007/s00005-023-00672-1
pmc: PMC9972324
doi:
Types de publication
Multicenter Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8Subventions
Organisme : Silesian University of Technology
ID : 32/007/SDU/10-21-02
Informations de copyright
© 2023. The Author(s).
Références
Adhyaru BB, Jacobson TA (2018) Safety and efficacy of statin therapy. Nat Rev Cardiol 15:757–769. https://doi.org/10.1038/s41569-018-0098-5
doi: 10.1038/s41569-018-0098-5
pubmed: 30375494
Ahmadi M, Amiri S, Pecic S et al (2020) Pleiotropic effects of statins: a focus on cancer. Biochim Biophys Acta Mol Basis Dis 1866:165968. https://doi.org/10.1016/j.bbadis.2020.165968
doi: 10.1016/j.bbadis.2020.165968
pubmed: 32927022
Alizadeh J, Zeki AA, Mirzaei N et al (2017) Mevalonate cascade inhibition by simvastatin induces the intrinsic apoptosis pathway via depletion of isoprenoids in tumor cells. Sci Rep 7:44841. https://doi.org/10.1038/srep44841
doi: 10.1038/srep44841
pubmed: 28344327
pmcid: 5366866
Alizadeh J, Glogowska A, Thliveris J et al (2018) 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 1865:749–768. https://doi.org/10.1016/j.bbamcr.2018.02.007
doi: 10.1016/j.bbamcr.2018.02.007
pubmed: 29481833
American Diabetes Association (2021) 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2021. Diabetes Care 44(Suppl 1):S15–S33. https://doi.org/10.2337/dc21-s002
doi: 10.2337/dc21-s002
American Diabetes Association Professional Practice Committee (2022) 10. Cardiovascular disease and risk management: standards of medical care in diabetes-2022. Diabetes Care 45(Suppl 1):S144–S174. https://doi.org/10.2337/dc22-er05
doi: 10.2337/dc22-er05
Araya J, Kojima J, Takasaka N et al (2013) Insufficient autophagy in idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 304:L56–L69. https://doi.org/10.1152/ajplung.00213.2012
doi: 10.1152/ajplung.00213.2012
pubmed: 23087019
Camiciottoli G, Orlandi I, Bartolucci M et al (2007) Lung CT densitometry in systemic sclerosis: correlation with lung function, exercise testing, and quality of life. Chest 131:672–681. https://doi.org/10.1378/chest.06-1401
doi: 10.1378/chest.06-1401
pubmed: 17356079
Cariou B, Goronflot T, Rimbert A et al (2021) Routine use of statins and increased COVID-19 related mortality in inpatients with type 2 diabetes: results from the CORONADO study. Diabetes Metab 47:101202. https://doi.org/10.1016/j.diabet.2020.10.001
doi: 10.1016/j.diabet.2020.10.001
pubmed: 33091555
Centers for Disease Control and Prevention (2020) Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). https://stacks.cdc.gov/view/cdc/89980
Centers for Disease Control and Prevention (2022) Underlying medical conditions associated with higher risk for severe COVID-19: information for healthcare professionals [Online]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html . Accessed 17/05/2022
Davoodi L, Jafarpour H, Oladi Z et al (2021) Atorvastatin therapy in COVID-19 adult inpatients: a double-blind, randomized controlled trial. Int J Cardiol Heart Vasc 36:100875. https://doi.org/10.1016/j.ijcha.2021.100875
doi: 10.1016/j.ijcha.2021.100875
pubmed: 34541293
pmcid: 8437805
Dhand R, Li J (2020) Coughs and sneezes: their role in transmission of respiratory viral infections, including SARS-CoV-2. Am J Respir Critical Care Med 202:651–659. https://doi.org/10.1164/rccm.202004-1263pp
doi: 10.1164/rccm.202004-1263pp
Drozdzal S, Rosik J, Lechowicz K et al (2021) An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment. Drug Resist Updat 59:100794. https://doi.org/10.1016/j.drup.2021.100794
doi: 10.1016/j.drup.2021.100794
pubmed: 34991982
pmcid: 8654464
Elahi S, Weiss RH, Merani S (2016) Atorvastatin restricts HIV replication in CD4+ T cells by upregulation of p21. AIDS 30:171–183. https://doi.org/10.1097/QAD.0000000000000917
doi: 10.1097/QAD.0000000000000917
pubmed: 26645604
Emami A, Shojaei S, Da Silva Rosa SC et al (2019) Mechanisms of simvastatin myotoxicity: the role of autophagy flux inhibition. Eur J Pharmacol 862:172616. https://doi.org/10.1016/j.ejphar.2019.172616
doi: 10.1016/j.ejphar.2019.172616
pubmed: 31449810
Gawish R, Starkl P, Pimenov L et al (2022) ACE2 is the critical in vivo receptor for SARS-CoV-2 in a novel COVID-19 mouse model with TNF- and IFNgamma-driven immunopathology. Elife 11:e74623. https://doi.org/10.7554/elife.74623
doi: 10.7554/elife.74623
pubmed: 35023830
pmcid: 8776253
George PM, Wells AU, Jenkins RG (2020) Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy. Lancet Respir Med 8:807–815. https://doi.org/10.1016/s2213-2600(20)30225-3
doi: 10.1016/s2213-2600(20)30225-3
pubmed: 32422178
pmcid: 7228727
Ghavami S, Mutawe MM, Schaafsma D et al (2012) Geranylgeranyl transferase 1 modulates autophagy and apoptosis in human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 302:L420–L428. https://doi.org/10.1152/ajplung.00312.2011
doi: 10.1152/ajplung.00312.2011
pubmed: 22160308
Ghavami S, Sharma P, Yeganeh B et al (2014) Airway mesenchymal cell death by mevalonate cascade inhibition: integration of autophagy, unfolded protein response and apoptosis focusing on Bcl2 family proteins. Biochim Biophys Acta 1843:1259–1271. https://doi.org/10.1016/j.bbamcr.2014.03.006
doi: 10.1016/j.bbamcr.2014.03.006
pubmed: 24637330
Ghavami S, Cunnington RH, Gupta S et al (2015) Autophagy is a regulator of TGF-beta1-induced fibrogenesis in primary human atrial myofibroblasts. Cell Death Dis 6:e1696. https://doi.org/10.1038/cddis.2015.36
doi: 10.1038/cddis.2015.36
pubmed: 25789971
pmcid: 4385916
Ghavami S, Yeganeh B, Zeki AA et al (2018) Autophagy and the unfolded protein response promote profibrotic effects of TGF-beta1 in human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol 314:L493–L504. https://doi.org/10.1152/ajplung.00372.2017
doi: 10.1152/ajplung.00372.2017
pubmed: 29074489
Gower TL, Graham BS (2001) Antiviral activity of lovastatin against respiratory syncytial virus in vivo and in vitro. Antimicrob Agents Chemother 45:1231–1237. https://doi.org/10.1128/AAC.45.4.1231-1237.2001
doi: 10.1128/AAC.45.4.1231-1237.2001
pubmed: 11257039
pmcid: 90448
Gu W, Cui R, Ding T et al (2017) Simvastatin alleviates airway inflammation and remodelling through up-regulation of autophagy in mouse models of asthma. Respirology 22:533–541. https://doi.org/10.1111/resp.12926
doi: 10.1111/resp.12926
pubmed: 27782356
Guo W, Li M, Dong Y et al (2020) Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev 36:e3319. https://doi.org/10.1002/dmrr.3319
doi: 10.1002/dmrr.3319
pubmed: 32233013
pmcid: 7228407
Habibzadeh P, Dastsooz H, Eshraghi M et al (2021) Autophagy: the potential link between SARS-CoV-2 and cancer. Cancers 13:5721. https://doi.org/10.3390/cancers13225721
doi: 10.3390/cancers13225721
pubmed: 34830876
pmcid: 8616402
Han F, Xiao QQ, Peng S et al (2018) Atorvastatin ameliorates LPS-induced inflammatory response by autophagy via AKT/mTOR signaling pathway. J Cell Biochem 119:1604–1615. https://doi.org/10.1002/jcb.26320
doi: 10.1002/jcb.26320
pubmed: 28771872
Hulme K, Dogan S, Parker SM et al (2019) ‘Chronic cough, cause unknown’: a qualitative study of patient perspectives of chronic refractory cough. J Health Psychol 24:707–716. https://doi.org/10.1177/1359105316684204
doi: 10.1177/1359105316684204
pubmed: 28810370
Hussain A, Bhowmik B, Do Vale Moreira NC (2020) COVID-19 and diabetes: Knowledge in progress. Diabetes Res Clin Pract 162:108142. https://doi.org/10.1016/j.diabres.2020.108142
doi: 10.1016/j.diabres.2020.108142
pubmed: 32278764
pmcid: 7144611
Jackson CB, Farzan M, Chen B et al (2022) Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol 23:3–20. https://doi.org/10.1038/s41580-021-00418-x
doi: 10.1038/s41580-021-00418-x
pubmed: 34611326
Jones RM, Hilldrup S, Hope-Gill BD et al (2011) Mechanical induction of cough in idiopathic pulmonary fibrosis. Cough 7:2. https://doi.org/10.1186/1745-9974-7-2
doi: 10.1186/1745-9974-7-2
pubmed: 21477349
pmcid: 3094358
Jutant EM, Meyrignac O, Beurnier A et al (2022) Respiratory symptoms and radiological findings in post-acute COVID-19 syndrome. ERJ Open Res 8:00479–02021. https://doi.org/10.1183/23120541.00479-2021
doi: 10.1183/23120541.00479-2021
pubmed: 35445129
pmcid: 8685862
Kim SW, Kang HJ, Jhon M et al (2019) Statins and Inflammation: New therapeutic opportunities in psychiatry. Front Psychiatry 10:103. https://doi.org/10.3389/fpsyt.2019.00103
doi: 10.3389/fpsyt.2019.00103
pubmed: 30890971
pmcid: 6413672
Kou L, Kou P, Luo G et al (2022) Progress of statin therapy in the treatment of idiopathic pulmonary fibrosis. Oxid Med Cell Longev 2022:6197219. https://doi.org/10.1155/2022/6197219
doi: 10.1155/2022/6197219
pubmed: 35345828
pmcid: 8957418
Kouhpayeh HR, Tabasi F, Dehvari M et al (2021) Association between angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and angiotensin-II receptor 1 (AGTR1) polymorphisms and COVID-19 infection in the southeast of Iran: a preliminary case–control study. Transl Med Commun 6:26. https://doi.org/10.1186/s41231-021-00106-0
doi: 10.1186/s41231-021-00106-0
pubmed: 34805533
pmcid: 8596349
Kreuter M, Bonella F, Maher TM et al (2017) Effect of statins on disease-related outcomes in patients with idiopathic pulmonary fibrosis. Thorax 72:148–153. https://doi.org/10.1136/thoraxjnl-2016-208819
doi: 10.1136/thoraxjnl-2016-208819
pubmed: 27708114
Kyrou I, Randeva HS, Spandidos DA et al (2021) Not only ACE2-the quest for additional host cell mediators of SARS-CoV-2 infection: neuropilin-1 (NRP1) as a novel SARS-CoV-2 host cell entry mediator implicated in COVID-19. Signal Transduct Target Ther 6:21. https://doi.org/10.1038/s41392-020-00460-9
doi: 10.1038/s41392-020-00460-9
pubmed: 33462185
pmcid: 7812344
Lachowicz-Scroggins ME, Dunican EM, Charbit AR et al (2019) Extracellular DNA, neutrophil extracellular traps, and inflammasome activation in severe asthma. Am J Respir Crit Care Med 199:1076–1085. https://doi.org/10.1164/rccm.201810-1869OC
doi: 10.1164/rccm.201810-1869OC
pubmed: 30888839
pmcid: 6515873
Lechowicz K, Drożdżal S, Machaj F et al (2020) COVID-19: the potential treatment of pulmonary fibrosis associated with SARS-CoV-2 infection. J Clin Med 9:1917. https://doi.org/10.3390/jcm9061917
doi: 10.3390/jcm9061917
pubmed: 32575380
pmcid: 7356800
Lee KCH, Sewa DW, Phua GC (2020) Potential role of statins in COVID-19. Int J Infect Dis 96:615–617. https://doi.org/10.1016/j.ijid.2020.05.115
doi: 10.1016/j.ijid.2020.05.115
pubmed: 32502659
pmcid: 7265877
Liao JK, Laufs U (2005) Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 45:89–118. https://doi.org/10.1146/annurev.pharmtox.45.120403.095748
doi: 10.1146/annurev.pharmtox.45.120403.095748
pubmed: 15822172
pmcid: 2694580
Lim S, Bae JH, Kwon HS et al (2021) COVID-19 and diabetes mellitus: from pathophysiology to clinical management. Nat Rev Endocrinol 17:11–30. https://doi.org/10.1038/s41574-020-00435-4
doi: 10.1038/s41574-020-00435-4
pubmed: 33188364
Lohia P, Kapur S, Benjaram S et al (2021) Statins and clinical outcomes in hospitalized COVID-19 patients with and without diabetes mellitus: a retrospective cohort study with propensity score matching. Cardiovasc Diabetol 20:140. https://doi.org/10.1186/s12933-021-01336-0
doi: 10.1186/s12933-021-01336-0
pubmed: 34246277
pmcid: 8272452
Loppnow H, Zhang L, Buerke M et al (2011) Statins potently reduce the cytokine-mediated IL-6 release in SMC/MNC cocultures. J Cell Mol Med 15:994–1004. https://doi.org/10.1111/j.1582-4934.2010.01036.x
doi: 10.1111/j.1582-4934.2010.01036.x
pubmed: 20158569
Meizlish ML, Pine AB, Bishai JD et al (2021) A neutrophil activation signature predicts critical illness and mortality in COVID-19. Blood Adv 5:1164–1177. https://doi.org/10.1182/bloodadvances.2020003568
doi: 10.1182/bloodadvances.2020003568
pubmed: 33635335
pmcid: 7908851
Parackova Z, Zentsova I, Bloomfield M et al (2020) Disharmonic inflammatory signatures in COVID-19: Augmented neutrophils’ but impaired monocytes’ and dendritic cells’ responsiveness. Cells 9:2206. https://doi.org/10.3390/cells9102206
doi: 10.3390/cells9102206
pubmed: 33003471
pmcid: 7600406
Pawlos A, Niedzielski M, Gorzelak-Pabiś P et al (2021) COVID-19: Direct and Indirect mechanisms of statins. Int J Mol Sci 22:4177. https://doi.org/10.3390/ijms22084177
doi: 10.3390/ijms22084177
pubmed: 33920709
pmcid: 8073792
Peng S, Xu LW, Che XY et al (2018) Atorvastatin inhibits inflammatory response, attenuates lipid deposition, and improves the stability of vulnerable atherosclerotic plaques by modulating autophagy. Front Pharmacol 9:438. https://doi.org/10.3389/fphar.2018.00438
doi: 10.3389/fphar.2018.00438
pubmed: 29773990
pmcid: 5943597
Peterson CL, Walker C (2022) Universal health care and political economy, neoliberalism and effects of COVID-19: a view of systems and complexity. J Eval Clin Pract 28:338–340. https://doi.org/10.1111/jep.13631
doi: 10.1111/jep.13631
pubmed: 34647671
Peymani P, Dehesh T, Aligolighasemabadi F et al (2021) Statins in patients with COVID-19: a retrospective cohort study in Iranian COVID-19 patients. Transl Med Commun 6:3. https://doi.org/10.1186/s41231-021-00082-5
doi: 10.1186/s41231-021-00082-5
pubmed: 33521322
pmcid: 7829327
Raveendran A, Misra A (2021) Post COVID-19 syndrome (“Long COVID”) and diabetes: challenges in diagnosis and management. Diabetes Metab Syndr 15:102235. https://doi.org/10.1016/j.dsx.2021.102235
doi: 10.1016/j.dsx.2021.102235
pubmed: 34384972
pmcid: 8317446
Reusch N, De Domenico E, Bonaguro L et al (2021) Neutrophils in COVID-19. Front Immunol 12:652470. https://doi.org/10.3389/fimmu.2021.652470
doi: 10.3389/fimmu.2021.652470
pubmed: 33841435
pmcid: 8027077
Saeed O, Castagna F, Agalliu I et al (2020) Statin use and in-hospital mortality in patients with diabetes mellitus and COVID-19. J Am Heart Assoc 9:e018475. https://doi.org/10.1161/JAHA.120.018475
doi: 10.1161/JAHA.120.018475
pubmed: 33092446
pmcid: 7955378
Santos A, Magro DO, Evangelista-Poderoso R et al (2021) Diabetes, obesity, and insulin resistance in COVID-19: molecular interrelationship and therapeutic implications. Diabetol Metab Syndr 13:23. https://doi.org/10.1186/s13098-021-00639-2
doi: 10.1186/s13098-021-00639-2
pubmed: 33648564
pmcid: 7919999
Satny M, Hubacek JA, Vrablik M (2021) Statins and inflammation. Curr Atheroscler Rep 23:80. https://doi.org/10.1007/s11883-021-00977-6
doi: 10.1007/s11883-021-00977-6
pubmed: 34851454
Schaafsma D, Dueck G, Ghavami S et al (2011a) The mevalonate cascade as a target to suppress extracellular matrix synthesis by human airway smooth muscle. Am J Respir Cell Mol Biol 44:394–403. https://doi.org/10.1165/rcmb.2010-0052oc
doi: 10.1165/rcmb.2010-0052oc
pubmed: 20463291
Schaafsma D, Mcneill KD, Mutawe MM et al (2011b) Simvastatin inhibits TGFbeta1-induced fibronectin in human airway fibroblasts. Respir Res 12:113. https://doi.org/10.1186/1465-9921-12-113
doi: 10.1186/1465-9921-12-113
pubmed: 21864337
pmcid: 3173339
Scheen AJ (2021) Statins and clinical outcomes with COVID-19: meta-analyses of observational studies. Diabetes Metab 47:101220. https://doi.org/10.1016/j.diabet.2020.101220
doi: 10.1016/j.diabet.2020.101220
pubmed: 33359486
Shojaei S, Koleini N, Samiei E et al (2020a) Simvastatin increases temozolomide-induced cell death by targeting the fusion of autophagosomes and lysosomes. FEBS J 287:1005–1034. https://doi.org/10.1111/febs.15069
doi: 10.1111/febs.15069
pubmed: 31545550
Shojaei S, Suresh M, Klionsky DJ et al (2020b) Autophagy and SARS-CoV-2 infection: a possible smart targeting of the autophagy pathway. Virulence 11:805–810. https://doi.org/10.1080/21505594.2020.1780088
doi: 10.1080/21505594.2020.1780088
pubmed: 32567972
pmcid: 7549903
Siri M, Dastghaib S, Zamani M et al (2021) Autophagy, unfolded protein response, and neuropilin-1 cross-talk in SARS-CoV-2 infection: what can be learned from other coronaviruses. Int J Mol Sci 22:5992. https://doi.org/10.3390/ijms22115992
doi: 10.3390/ijms22115992
pubmed: 34206057
pmcid: 8199451
Song WJ, Hui CKM, Hull JH et al (2021) Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses. Lancet Respir Med 9:533–544. https://doi.org/10.1016/s2213-2600(21)00125-9
doi: 10.1016/s2213-2600(21)00125-9
pubmed: 33857435
pmcid: 8041436
Taefehshokr N, Taefehshokr S, Hemmat N et al (2020) Covid-19: perspectives on innate immune evasion. Front Immunol 11:580641. https://doi.org/10.3389/fimmu.2020.580641
doi: 10.3389/fimmu.2020.580641
pubmed: 33101306
pmcid: 7554241
Walls AC, Park YJ, Tortorici MA et al (2020) Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 181:281-292.e6. https://doi.org/10.1016/j.cell.2020.02.058
doi: 10.1016/j.cell.2020.02.058
pubmed: 32155444
pmcid: 7102599
Watts KL, Sampson EM, Schultz GS et al (2005) Simvastatin inhibits growth factor expression and modulates profibrogenic markers in lung fibroblasts. Am J Respir Cell Mol Biol 32:290–300. https://doi.org/10.1165/rcmb.2004-0127oc
doi: 10.1165/rcmb.2004-0127oc
pubmed: 15677772
Winslow S, Odqvist L, Diver S et al (2021) Multi-omics links IL-6 trans-signalling with neutrophil extracellular trap formation and Haemophilus infection in COPD. Eur Respir J 58:2003312. https://doi.org/10.1183/13993003.03312-2020
doi: 10.1183/13993003.03312-2020
pubmed: 33766947
Yang T, Chen M, Sun T (2013) Simvastatin attenuates TGF-β1-induced epithelial–mesenchymal transition in human alveolar epithelial cells. Cell Physiol Biochem 31:863–874. https://doi.org/10.1159/000350104
doi: 10.1159/000350104
pubmed: 23817018
Yang J, Zheng Y, Gou X et al (2020) Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis 94:91–95. https://doi.org/10.1016/j.ijid.2020.03.017
doi: 10.1016/j.ijid.2020.03.017
pubmed: 32173574
pmcid: 7194638
Yavarian J, Nejati A, Salimi V et al (2022) Whole genome sequencing of SARS-CoV2 strains circulating in Iran during five waves of pandemic. PLoS ONE 17:e0267847. https://doi.org/10.1371/journal.pone.0267847
doi: 10.1371/journal.pone.0267847
pubmed: 35499994
pmcid: 9060343