{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T23:46:51Z","timestamp":1782863211054,"version":"3.54.5"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":55,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100004612","name":"Funda\u00e7\u00e3o Arauc\u00e1ria","doi-asserted-by":"publisher","award":["PPSUS"],"award-info":[{"award-number":["PPSUS"]}],"id":[{"id":"10.13039\/501100004612","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["INCT-CERBC\/Brazil n\u00b0406645\/2022-1"],"award-info":[{"award-number":["INCT-CERBC\/Brazil n\u00b0406645\/2022-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["Code 001"],"award-info":[{"award-number":["Code 001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Med"],"DOI":"10.1186\/s10020-026-01467-8","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T15:44:03Z","timestamp":1778168643000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic and microRNA-mediated regulation of pulmonary fibrosis and immune dysregulation in fatal COVID-19"],"prefix":"10.1186","volume":"32","author":[{"given":"Gabriela Casani","family":"Cardoso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regiane Stafim","family":"da Cunha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme","family":"Miniskiskosky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cleber","family":"Machado-Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"de Noronha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline Busatta Vaz","family":"de Paula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe Francisco","family":"Tuon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edneia Amancio","family":"de Souza Ramos Cavalieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"1467_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03553-9","author":"Z Al-Aly","year":"2021","unstructured":"Al-Aly Z, Xie Y, Bowe B. High-dimensional characterization of post-acute sequelae of COVID-19. Nature. 2021. https:\/\/doi.org\/10.1038\/s41586-021-03553-9.","journal-title":"Nature"},{"key":"1467_CR2","doi-asserted-by":"publisher","unstructured":"Baldi1,2 BG, Erico Tanni3 S. Pulmonary fibrosis and follow-up of COVID-19 survivors: an urgent need for clarification. Jornal Brasileiro de Pneumologia 2021:e2021. https:\/\/doi.org\/10.36416\/1806-3756\/e20210213.","DOI":"10.36416\/1806-3756\/e20210213"},{"key":"1467_CR3","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-021-01102-9","author":"J Balnis","year":"2021","unstructured":"Balnis J, Madrid A, Hogan KJ, Drake LA, Chieng HC, Tiwari A, et al. Blood DNA methylation and COVID-19 outcomes. Clin Epigenetics. 2021. https:\/\/doi.org\/10.1186\/s13148-021-01102-9.","journal-title":"Clin Epigenetics"},{"key":"1467_CR4","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/j.jcv.2014.10.004","volume":"61","author":"E Baurakiades","year":"2014","unstructured":"Baurakiades E, Costa VH, Raboni SM, de Almeida VRT, Larsen KSK, Kohler JN, et al. The roles of ADAM33, ADAM28, IL-13 and IL-4 in the development of lung injuries in children with lethal non-pandemic acute infectious pneumonia. J Clin Virol. 2014;61:585\u20139. https:\/\/doi.org\/10.1016\/j.jcv.2014.10.004.","journal-title":"J Clin Virol"},{"key":"1467_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/S12967-022-03737-5\/FIGURES\/10","volume":"20","author":"M Bradic","year":"2022","unstructured":"Bradic M, Taleb S, Thomas B, Chidiac O, Robay A, Hassan N, et al. DNA methylation predicts the outcome of COVID-19 patients with acute respiratory distress syndrome. J Transl Med. 2022;20:1\u201318. https:\/\/doi.org\/10.1186\/S12967-022-03737-5\/FIGURES\/10.","journal-title":"J Transl Med"},{"key":"1467_CR6","doi-asserted-by":"publisher","DOI":"10.1515\/bmc-2022-0041","author":"GC Cardoso","year":"2024","unstructured":"Cardoso GC, Ganzella FAdeO, Miniskiskosky G, da Cunha RS, Ramos EAdeS. Digital methylation-specific PCR: new applications for liquid biopsy. Biomol Concepts. 2024. https:\/\/doi.org\/10.1515\/bmc-2022-0041.","journal-title":"Biomol Concepts"},{"key":"1467_CR7","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1096\/FASEBJ.10.4.8647346","volume":"10","author":"PK Chiang","year":"1996","unstructured":"Chiang PK, Gordon RK, Tal J, Zeng GC, Doctor BP, Pardhasaradhi K, et al. S-Adenosylmethionine and methylation. FASEB J. 1996;10:471\u201380. https:\/\/doi.org\/10.1096\/FASEBJ.10.4.8647346.","journal-title":"FASEB J"},{"key":"1467_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/J.BIOPHA.2021.112067","author":"C D`Avila-Mesquita","year":"2021","unstructured":"D`Avila-Mesquita C, Couto AES, Campos LCB, Vasconcelos TF, Michelon-Barbosa J, Corsi CAC, et al. MMP-2 and MMP-9 levels in plasma are altered and associated with mortality in COVID-19 patients. Biomed Pharmacother. 2021. https:\/\/doi.org\/10.1016\/J.BIOPHA.2021.112067.","journal-title":"Biomed Pharmacother"},{"key":"1467_CR9","doi-asserted-by":"publisher","first-page":"105357","DOI":"10.1016\/j.meegid.2022.105357","volume":"104","author":"G Daniel","year":"2022","unstructured":"Daniel G, Paola A-R, Nancy G, Fernando S-O, Beatriz A, Zulema R, et al. Epigenetic mechanisms and host factors impact ACE2 gene expression: implications in COVID-19 susceptibility. Infect Genet Evol. 2022;104:105357. https:\/\/doi.org\/10.1016\/j.meegid.2022.105357.","journal-title":"Infect Genet Evol"},{"key":"1467_CR10","doi-asserted-by":"publisher","unstructured":"Davies ER, Kelly JFC, Howarth PH, Wilson DI, Holgate ST, Davies DE, et al. Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life. JCI Insight 2016;1. https:\/\/doi.org\/10.1172\/JCI.INSIGHT.87632.","DOI":"10.1172\/JCI.INSIGHT.87632"},{"key":"1467_CR11","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1152\/ajplung.00294.2014","volume":"308","author":"D Dreymueller","year":"2015","unstructured":"Dreymueller D, Uhlig S, Ludwig A. ADAM-family metalloproteinases in lung inflammation: potential therapeutic targets. Am J Physiol Lung Cell Mol Physiol. 2015;308:325\u201343. https:\/\/doi.org\/10.1152\/ajplung.00294.2014.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"1467_CR12","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.3390\/microorganisms12071304","volume":"12","author":"C Fern\u00e1ndez-de-las-Pe\u00f1as","year":"2024","unstructured":"Fern\u00e1ndez-de-las-Pe\u00f1as C, D\u00edaz-Gil G, Gil-Crujera A, G\u00f3mez-S\u00e1nchez SM, Ambite-Quesada S, Torres-Macho J, et al. DNA methylation levels of the ACE2 promoter are not associated with post-COVID-19 symptoms in individuals who had been hospitalized due to COVID-19. Microorganisms. 2024;12:1304. https:\/\/doi.org\/10.3390\/microorganisms12071304.","journal-title":"Microorganisms"},{"key":"1467_CR13","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1080\/22221751.2022.2038021","volume":"11","author":"A Fern\u00e1ndez-Pato","year":"2022","unstructured":"Fern\u00e1ndez-Pato A, Virseda-Berdices A, Resino S, Ryan P, Mart\u00ednez-Gonz\u00e1lez O, P\u00e9rez-Garc\u00eda F, et al. Plasma miRNA profile at COVID-19 onset predicts severity status and mortality. Emerg Microbes Infect. 2022;11:676\u201388. https:\/\/doi.org\/10.1080\/22221751.2022.2038021.","journal-title":"Emerg Microbes Infect"},{"key":"1467_CR14","doi-asserted-by":"publisher","DOI":"10.1186\/S13148-021-01022-8","author":"C Fern\u00e1ndez-Ponce","year":"2021","unstructured":"Fern\u00e1ndez-Ponce C, Navarro Quiroz R, D\u00edaz Perez A, Aroca Martinez G, Cadena Bonfanti A, Acosta Hoyos A, et al. Micrornas overexpressed in Crohn\u2019s disease and their interactions with mechanisms of epigenetic regulation explain novel aspects of Crohn\u2019s disease pathogenesis. Clin Epigenetics. 2021. https:\/\/doi.org\/10.1186\/S13148-021-01022-8.","journal-title":"Clin Epigenetics"},{"key":"1467_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/S10020-025-01154-0\/TABLES\/2","volume":"31","author":"M Gajate-Arenas","year":"2025","unstructured":"Gajate-Arenas M, Sirvent-Blanco C, Garc\u00eda-P\u00e9rez O, Dom\u00ednguez-de-Barros A, Pi\u00f1ero JE, Lorenzo-Morales J, et al. miR-27a-5p, miR-21-5p, miR-1246 and miR-4508: a candidate microRNA signature in the protection and regulation of viral infection in mild COVID-19. Mol Med. 2025;31:1\u201310. https:\/\/doi.org\/10.1186\/S10020-025-01154-0\/TABLES\/2.","journal-title":"Mol Med"},{"key":"1467_CR16","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1182\/BLOODADVANCES.2017006163","volume":"1","author":"M Gatica-Andrades","year":"2017","unstructured":"Gatica-Andrades M, Vagenas D, Kling J, Nguyen TTK, Benham H, Thomas R, et al. WNT ligands contribute to the immune response during septic shock and amplify endotoxemia-driven inflammation in mice. Blood Adv. 2017;1:1274\u201386. https:\/\/doi.org\/10.1182\/BLOODADVANCES.2017006163.","journal-title":"Blood Adv"},{"key":"1467_CR17","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2022.968991","author":"A Giannella","year":"2022","unstructured":"Giannella A, Riccetti S, Sinigaglia A, Piubelli C, Razzaboni E, Di Battista P, et al. Circulating microRNA signatures associated with disease severity and outcome in COVID-19 patients. Front Immunol. 2022. https:\/\/doi.org\/10.3389\/FIMMU.2022.968991.","journal-title":"Front Immunol"},{"key":"1467_CR18","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/S12931-023-02413-6","volume":"24","author":"J Guiot","year":"2023","unstructured":"Guiot J, Henket M, Remacle C, Cambier M, Struman I, Winandy M, et al. Systematic review of overlapping microrna patterns in COVID-19 and idiopathic pulmonary fibrosis. Respir Res. 2023;24:112. https:\/\/doi.org\/10.1186\/S12931-023-02413-6.","journal-title":"Respir Res"},{"key":"1467_CR19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.918881","author":"JF Hedges","year":"2022","unstructured":"Hedges JF, Snyder DT, Robison A, Grifka-Walk HM, Blackwell K, Shepardson K, et al. An ADAM17-neutralizing antibody reduces inflammation and mortality while increasing viral burden in a COVID-19 mouse model. Front Immunol. 2022. https:\/\/doi.org\/10.3389\/fimmu.2022.918881.","journal-title":"Front Immunol"},{"issue":"1","key":"1467_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-022-20834-z","volume":"12","author":"EH Hong","year":"2022","unstructured":"Hong EH, Hwang M, Yu H, Park HH, Cho H, Koh SH, et al. Differential expression of aqueous humor microRNAs in central retinal vein occlusion and its association with matrix metalloproteinases: a pilot study. Sci Rep. 2022;12(1):1\u201310. https:\/\/doi.org\/10.1038\/s41598-022-20834-z.","journal-title":"Sci Rep"},{"key":"1467_CR21","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1042\/CS20200476","volume":"134","author":"NM Hooper","year":"2020","unstructured":"Hooper NM, Lambert DW, Turner AJ. Discovery and characterization of ACE2 \u2013 a 20-year journey of surprises from vasopeptidase to COVID-19. Clin Sci. 2020;134:2489\u2013501. https:\/\/doi.org\/10.1042\/CS20200476.","journal-title":"Clin Sci"},{"key":"1467_CR22","doi-asserted-by":"publisher","unstructured":"Jackson RJ, Standart N. How do microRNAs regulate gene expression? Sci STKE 2007;2007. https:\/\/doi.org\/10.1126\/STKE.3672007RE1.","DOI":"10.1126\/STKE.3672007RE1"},{"key":"1467_CR23","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.gene.2017.11.054","volume":"642","author":"LMB Klassen","year":"2018","unstructured":"Klassen LMB, Chequin A, Manica GCM, Biembengut IV, Toledo MB, Baura VA, et al. MMP9 gene expression regulation by intragenic epigenetic modifications in breast cancer. Gene. 2018;642:461\u20136. https:\/\/doi.org\/10.1016\/j.gene.2017.11.054.","journal-title":"Gene"},{"key":"1467_CR24","doi-asserted-by":"publisher","DOI":"10.1101\/2025.04.16.25325949","author":"SL Lage","year":"2025","unstructured":"Lage SL, Bricker-Holt K, Rocco JM, Rupert A, Donovan FX, Abramzon YA, et al. Persistent immune dysregulation and metabolic alterations following SARS-CoV-2 infection. MedRxiv. 2025. https:\/\/doi.org\/10.1101\/2025.04.16.25325949.","journal-title":"MedRxiv"},{"key":"1467_CR25","doi-asserted-by":"publisher","first-page":"30113","DOI":"10.1074\/jbc.M505111200","volume":"280","author":"DW Lambert","year":"2005","unstructured":"Lambert DW, Yarski M, Warner FJ, Thornhill P, Parkin ET, Smith AI, et al. Tumor Necrosis Factor-\u03b1 Convertase (ADAM17) Mediates Regulated Ectodomain Shedding of the Severe-acute Respiratory Syndrome-Coronavirus (SARS-CoV) Receptor, Angiotensin-converting Enzyme-2 (ACE2)*. J Biol Chem. 2005;280:30113\u20139. https:\/\/doi.org\/10.1074\/jbc.M505111200.","journal-title":"J Biol Chem"},{"key":"1467_CR26","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/j.jid.2020.06.037","volume":"141","author":"D Li","year":"2021","unstructured":"Li D, Peng H, Qu L, Sommar P, Wang A, Chu T, et al. Mir-19a\/b and mir-20a promote wound healing by regulating the inflammatory response of keratinocytes. J Invest Dermatol. 2021;141:659\u201371. https:\/\/doi.org\/10.1016\/j.jid.2020.06.037.","journal-title":"J Invest Dermatol"},{"key":"1467_CR27","doi-asserted-by":"publisher","DOI":"10.1186\/2045-3701-4-46","author":"RK Lin","year":"2014","unstructured":"Lin RK, Wang YC. Dysregulated transcriptional and post-translational control of DNA methyltransferases in cancer. Cell Biosci. 2014. https:\/\/doi.org\/10.1186\/2045-3701-4-46.","journal-title":"Cell Biosci"},{"key":"1467_CR28","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/J.SEMCDB.2019.12.010","volume":"101","author":"M Lodyga","year":"2020","unstructured":"Lodyga M, Hinz B. TGF-\u03b21 \u2013 a truly transforming growth factor in fibrosis and immunity. Semin Cell Dev Biol. 2020;101:123\u201339. https:\/\/doi.org\/10.1016\/J.SEMCDB.2019.12.010.","journal-title":"Semin Cell Dev Biol"},{"key":"1467_CR29","doi-asserted-by":"publisher","first-page":"14","DOI":"10.4172\/1948-5956.1000178","volume":"5","author":"GCM Manica","year":"2013","unstructured":"Manica GCM, Ramos EAS, de Oliveira MAS, Costa FF, Pedrosa FdeO, de Souza EM. ADAM33 as a new biomarker for invasive lobular breast carcinoma. J Cancer Sci Ther. 2013;5:14\u20137. https:\/\/doi.org\/10.4172\/1948-5956.1000178.","journal-title":"J Cancer Sci Ther"},{"key":"1467_CR30","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/nri.2016.40","volume":"16","author":"A Mehta","year":"2016","unstructured":"Mehta A, Baltimore D. Micrornas as regulatory elements in immune system logic. Nat Rev Immunol. 2016;16:279\u201394. https:\/\/doi.org\/10.1038\/nri.2016.40.","journal-title":"Nat Rev Immunol"},{"key":"1467_CR31","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.622271","author":"JS Muhammad","year":"2021","unstructured":"Muhammad JS, Saheb Sharif-Askari N, Cui ZG, Hamad M, Halwani R. Sars-CoV-2 infection-induced promoter hypomethylation as an epigenetic modulator of heat shock protein A1L (HSPA1L) gene. Front Genet. 2021. https:\/\/doi.org\/10.3389\/fgene.2021.622271.","journal-title":"Front Genet"},{"key":"1467_CR32","doi-asserted-by":"publisher","unstructured":"Nicoletti A de S, Visacri MB, da Ronda CR da SC, Vasconcelos PE do NS, Quintanilha JCF, de Souza RN, et al. Differentially expressed plasmatic microRNAs in Brazilian patients with Coronavirus disease 2019 (COVID-19): preliminary results. Mol Biol Rep 2022;49:6931\u201343. https:\/\/doi.org\/10.1007\/S11033-022-07338-9\/FIGURES\/5.","DOI":"10.1007\/S11033-022-07338-9\/FIGURES\/5"},{"key":"1467_CR33","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/s0092-8674(00)81656-6","volume":"99","author":"M Okano","year":"1999","unstructured":"Okano M, Bell DW, Haber DA, Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999;99:247\u201357. https:\/\/doi.org\/10.1016\/s0092-8674(00)81656-6.","journal-title":"Cell"},{"key":"1467_CR34","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1016\/J.CHOM.2020.05.008","volume":"27","author":"A Park","year":"2020","unstructured":"Park A, Iwasaki A. Type I and type III interferons - induction, signaling, evasion, and application to combat COVID-19. Cell Host Microbe. 2020;27:870\u20138. https:\/\/doi.org\/10.1016\/J.CHOM.2020.05.008.","journal-title":"Cell Host Microbe"},{"key":"1467_CR35","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/J.LFS.2011.06.008","volume":"89","author":"DW Perng","year":"2011","unstructured":"Perng DW, Chang KT, Su KC, Wu YC, Chen CS, Hsu WH, et al. Matrix metalloprotease-9 induces transforming growth factor-\u03b2(1) production in airway epithelium via activation of epidermal growth factor receptors. Life Sci. 2011;89:204\u201312. https:\/\/doi.org\/10.1016\/J.LFS.2011.06.008.","journal-title":"Life Sci"},{"key":"1467_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2013.09.001","author":"FM Piccolo","year":"2014","unstructured":"Piccolo FM, Fisher AG. Getting rid of DNA methylation. Trends Cell Biol. 2014. https:\/\/doi.org\/10.1016\/j.tcb.2013.09.001.","journal-title":"Trends Cell Biol"},{"key":"1467_CR37","doi-asserted-by":"publisher","first-page":"2007","DOI":"10.3390\/biomedicines10082007","volume":"10","author":"CA Pomar","year":"2022","unstructured":"Pomar CA, Bonet ML, Ferre-Beltr\u00e1n A, Fraile-Ribot PA, Garc\u00eda-Gasalla M, Riera M, et al. Increased mRNA levels of ADAM17, IFITM3, and IFNE in peripheral blood cells are present in patients with obesity and may predict severe COVID-19 evolution. Biomedicines. 2022;10:2007. https:\/\/doi.org\/10.3390\/biomedicines10082007.","journal-title":"Biomedicines"},{"key":"1467_CR38","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1590\/1806-9282.62.08.774","volume":"62","author":"EAS Ramos","year":"2016","unstructured":"Ramos EAS, Da Silva CT, Manica GCM, Pereira IT, Klassen LMB, Ribeiro EMSF, et al. Worse prognosis in breast cancer patients can be predicted by immunohistochemical analysis of positive MMP-2 and negative estrogen and progesterone receptors. Rev Assoc Med Bras. 2016;62:774\u201381. https:\/\/doi.org\/10.1590\/1806-9282.62.08.774.","journal-title":"Rev Assoc Med Bras"},{"key":"1467_CR39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00705-023-05722-9","volume":"168","author":"S Salem","year":"2023","unstructured":"Salem S, Mosaad R, Lotfy R, Elbadry M. Altered expression of DNA methyltransferases and methylation status of the TLR4 and TNF-\u03b1 promoters in COVID-19. Arch Virol. 2023;168:1\u20138. https:\/\/doi.org\/10.1007\/s00705-023-05722-9.","journal-title":"Arch Virol"},{"key":"1467_CR40","doi-asserted-by":"publisher","first-page":"9089","DOI":"10.3390\/IJMS26189089","volume":"26","author":"L Santinelli","year":"2025","unstructured":"Santinelli L, Gentilini Cacciola E, Bortolani L, Ridolfi M, Maddaloni L, Frasca F, et al. Long COVID and type I IFN signature in working-age adults: a cross-sectional study. Int J Mol Sci. 2025;26:9089\u20139089. https:\/\/doi.org\/10.3390\/IJMS26189089.","journal-title":"Int J Mol Sci"},{"key":"1467_CR41","doi-asserted-by":"publisher","first-page":"685196","DOI":"10.3389\/FCHEM.2021.685196\/BIBTEX","volume":"9","author":"AF Santos","year":"2021","unstructured":"Santos AF, P\u00f3voa P, Paix\u00e3o P, Mendon\u00e7a A, Taborda-Barata L. Changes in glycolytic pathway in SARS-COV 2 infection and their importance in understanding the severity of COVID-19. Front Chem. 2021;9:685196. https:\/\/doi.org\/10.3389\/FCHEM.2021.685196\/BIBTEX.","journal-title":"Front Chem"},{"key":"1467_CR42","doi-asserted-by":"publisher","first-page":"108410","DOI":"10.1016\/j.clim.2020.108410","volume":"215","author":"AH Sawalha","year":"2020","unstructured":"Sawalha AH, Zhao M, Coit P, Lu Q. Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients. Clin Immunol. 2020;215:108410. https:\/\/doi.org\/10.1016\/j.clim.2020.108410.","journal-title":"Clin Immunol"},{"key":"1467_CR43","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-9-80","author":"GG Seniski","year":"2009","unstructured":"Seniski GG, Camargo AA, Ierardi DF, Ramos EAS, Grochoski M, Ribeiro ESF, et al. ADAM33 gene silencing by promoter hypermethylation as a molecular marker in breast invasive lobular carcinoma. BMC Cancer. 2009. https:\/\/doi.org\/10.1186\/1471-2407-9-80.","journal-title":"BMC Cancer"},{"key":"1467_CR44","doi-asserted-by":"publisher","DOI":"10.1016\/J.CRMICR.2021.100079","author":"DV Sethumadhavan","year":"2021","unstructured":"Sethumadhavan DV, Jabeena CA, Govindaraju G, Soman A, Rajavelu A. The severity of SARS-CoV-2 infection is dictated by host factors? Epigenetic perspectives. Curr Res Microb Sci. 2021. https:\/\/doi.org\/10.1016\/J.CRMICR.2021.100079.","journal-title":"Curr Res Microb Sci"},{"key":"1467_CR45","doi-asserted-by":"publisher","DOI":"10.1016\/J.CLIM.2025.110656","author":"C Sidiropoulou","year":"2026","unstructured":"Sidiropoulou C, Poulakou G, Kyriazopoulou E, Tasouli E, Giannitsioti E, Strikou A, et al. Long-term immune and epigenetic dysregulation following COVID-19. Clin Immunol. 2026. https:\/\/doi.org\/10.1016\/J.CLIM.2025.110656.","journal-title":"Clin Immunol"},{"issue":"4","key":"1467_CR46","doi-asserted-by":"publisher","first-page":"2318","DOI":"10.3390\/IJMS25042318","volume":"25","author":"J Sleziak","year":"2024","unstructured":"Sleziak J, Gawor A, B\u0142a\u017cejewska M, Antosz K, Gomu\u0142ka K. ADAM33\u2032s role in asthma pathogenesis: an overview. Int J Mol Sci. 2024;25(4):2318. https:\/\/doi.org\/10.3390\/IJMS25042318.","journal-title":"Int J Mol Sci"},{"key":"1467_CR47","doi-asserted-by":"publisher","DOI":"10.1038\/S41598-018-34839-0","author":"K Souma","year":"2018","unstructured":"Souma K, Shichino S, Hashimoto S, Ueha S, Tsukui T, Nakajima T, et al. Lung fibroblasts express a miR-19a-19b-20a sub-cluster to suppress TGF-\u03b2-associated fibroblast activation in murine pulmonary fibrosis. Sci Rep. 2018. https:\/\/doi.org\/10.1038\/S41598-018-34839-0.","journal-title":"Sci Rep"},{"key":"1467_CR48","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00182-17","author":"T Venkataraman","year":"2017","unstructured":"Venkataraman T, Coleman CM, Frieman MB. Overactive epidermal growth factor receptor signaling leads to increased fibrosis after severe acute respiratory syndrome Coronavirus infection. J Virol. 2017. https:\/\/doi.org\/10.1128\/JVI.00182-17.","journal-title":"J Virol"},{"key":"1467_CR49","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1093\/IJE\/DYR184","volume":"41","author":"CH Waddington","year":"2012","unstructured":"Waddington CH. The epigenotype. 1942. Int J Epidemiol. 2012;41:10\u20133. https:\/\/doi.org\/10.1093\/IJE\/DYR184.","journal-title":"Int J Epidemiol"},{"key":"1467_CR50","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3390\/IJMS24032524\/S1","volume":"24","author":"Y Wang","year":"2023","unstructured":"Wang Y, Schughart K, Pelaia TM, Chew T, Kim K, Karvunidis T, et al. Pathway and network analyses identify growth factor signaling and MMP9 as potential mediators of mitochondrial dysfunction in severe COVID-19. Int J Mol Sci. 2023;24:10. https:\/\/doi.org\/10.3390\/IJMS24032524\/S1.","journal-title":"Int J Mol Sci"},{"key":"1467_CR51","doi-asserted-by":"publisher","first-page":"103672","DOI":"10.1016\/J.ISCI.2021.103672","volume":"25","author":"JC Wilson","year":"2022","unstructured":"Wilson JC, Kealy D, James SR, Plowman T, Newling K, Jagger C, et al. Integrated miRNA\/cytokine\/chemokine profiling reveals severity-associated step changes and principal correlates of fatality in COVID-19. Iscience. 2022;25:103672. https:\/\/doi.org\/10.1016\/J.ISCI.2021.103672.","journal-title":"Iscience"},{"key":"1467_CR52","doi-asserted-by":"publisher","DOI":"10.3389\/FVIRO.2024.1371683","author":"Y Xiao","year":"2024","unstructured":"Xiao Y, Vermund SH. DNA methylation in long COVID. Front Virol. 2024. https:\/\/doi.org\/10.3389\/FVIRO.2024.1371683.","journal-title":"Front Virol"},{"key":"1467_CR53","doi-asserted-by":"publisher","first-page":"571","DOI":"10.21037\/ATM-22-1897","volume":"10","author":"W Xiao","year":"2022","unstructured":"Xiao W, Jiang Z, Wan W, Pan W, Xu J. miR-145-5p targets MMP2 to protect brain injury in hypertensive intracerebral hemorrhage via inactivation of the Wnt\/\u03b2-catenin signaling pathway. Ann Transl Med. 2022;10:571\u2013571. https:\/\/doi.org\/10.21037\/ATM-22-1897.","journal-title":"Ann Transl Med"},{"issue":"6","key":"1467_CR54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41419-019-1713-z","volume":"10","author":"Z Xue","year":"2019","unstructured":"Xue Z, Xi Q, Liu H, Guo X, Zhang J, Zhang Z, et al. miR-21 promotes NLRP3 inflammasome activation to mediate pyroptosis and endotoxic shock. Cell Death Dis. 2019;10(6):1\u201313. https:\/\/doi.org\/10.1038\/s41419-019-1713-z.","journal-title":"Cell Death Dis"},{"key":"1467_CR55","doi-asserted-by":"publisher","first-page":"3371","DOI":"10.1111\/iwj.14169","volume":"20","author":"L Yu","year":"2023","unstructured":"Yu L, Wang Y, Ma D, Pan L, Liu X, Chu T, et al. In-hospital nursing care intervention increasing the effect of vacuum sealing drainage on wound healing: a meta-analysis. Int Wound J. 2023;20:3371\u20139. https:\/\/doi.org\/10.1111\/iwj.14169.","journal-title":"Int Wound J"},{"key":"1467_CR56","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e37801","author":"Q Zeng","year":"2024","unstructured":"Zeng Q, Shi W, Xie L, Dai Y, Wei C. TGF-\u03b21\/miR-30d-5p axis regulating the expression of EMT key factors to induce apoptosis of lung cancer cells. Heliyon. 2024. https:\/\/doi.org\/10.1016\/j.heliyon.2024.e37801.","journal-title":"Heliyon"},{"key":"1467_CR57","doi-asserted-by":"publisher","first-page":"177","DOI":"10.33549\/physiolres.934754","volume":"70","author":"J Zlack\u00e1","year":"2021","unstructured":"Zlack\u00e1 J, Stebelov\u00e1 K, Zeman M, Herichov\u00e1 I, Herichov\u00e1 I. Interactions of renin-angiotensin system and COVID-19: the importance of daily rhythms in ACE2, ADAM17 and TMPRSS2 expression. Physiol Res. 2021;70:177\u201394. https:\/\/doi.org\/10.33549\/physiolres.934754.","journal-title":"Physiol Res"}],"container-title":["Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s10020-026-01467-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10020-026-01467-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10020-026-01467-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T22:48:59Z","timestamp":1782859739000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s10020-026-01467-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,7]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1467"],"URL":"https:\/\/doi.org\/10.1186\/s10020-026-01467-8","relation":{},"ISSN":["1528-3658"],"issn-type":[{"value":"1528-3658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,7]]},"assertion":[{"value":"14 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent was obtained from physicians to use specific clinical information for the study cohort. Eligible patients were included in the study only after providing consent. Permission was obtained from the families of patients since the biopsies were performed after the fatal outcome. This study was previously approved by the Brazilian Research Ethics Committees (CONEP) under the registration number CAAE 38803220.1.0000.0096.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval statement and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consenting for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"97"}}