{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:41:49Z","timestamp":1766050909259,"version":"build-2065373602"},"reference-count":56,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ARM"],"abstract":"<jats:p>The therapeutic target of COVID-19 is focused on controlling inflammation and preventing fibrosis. Collagen\u2013polyvinylpyrrolidone (collagen-PVP) and pirfenidone both have the ability to control the cytokine storm observed in rheumatic and fibrotic disorders. In this work, our aim was to understand the benefits of treatment with each of these drugs in patients with severe COVID-19. In total, 36 patients were treated with dexamethasone and enoxaparin, but 26 were allocated collagen-PVP or pirfenidone (n = 15 and 11, respectively); the clinical and metabolic effects were compared among them. Since pirfenidone works via transcriptional mechanisms, we performed a human genome microarray assay using RNA isolated from fibroblast and monocyte cultures treated with the biodrug, with the aim of hypothesising a possible mechanism of action for collagen-PVP. Our results showed that hospital stay duration, quick COVID-19 severity index (qCSI), and admission to the intensive care unit were statistically significantly lower (p &lt; 0.02) in patients treated with collagen-PVP or pirfenidone when compared with the control group, and that only collagen-PVP normalised serum glucose at discharge. Ingenuity Pathway Analysis showed that the cell cycle, inflammation, and cell surface\u2013extracellular matrix interactions could be regulated with collagen-PVP via the downmodulation of proinflammatory cytokines, while Th2 anti-inflammatory response signalling could be upregulated. Furthermore, the downregulation of some of the genes involved in nitric oxide production showed a possible control for JAK in the IFN-\u03b3 pathway, allowing for the possibility of controlling inflammation through the JAK\/STAT pathway, as has been observed for pirfenidone and other immunomodulators, such as ruxolitinib.<\/jats:p>","DOI":"10.3390\/arm93040024","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T10:10:38Z","timestamp":1752833438000},"page":"24","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacological Immunomodulation via Collagen\u2013Polyvinylpyrrolidone or Pirfenidone Plays a Role in the Recovery of Patients with Severe COVID-19 Through Similar Mechanisms of Action Involving the JAK\/STAT Signalling Pathway: A Pilot Study"],"prefix":"10.3390","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3492-8950","authenticated-orcid":false,"given":"Hugo","family":"Mendieta-Zer\u00f3n","sequence":"first","affiliation":[{"name":"Facultad de Medicina, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50000, State of Mexico, Mexico"},{"name":"Hospital Materno-Perinatal \u2018M\u00f3nica Pretelini S\u00e1enz\u2019, Toluca 50140, State of Mexico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0238-9518","authenticated-orcid":false,"given":"Esteban","family":"Cruz-Arenas","sequence":"additional","affiliation":[{"name":"Epidemiological Vigilance Unit, Instituto Nacional de Rehabilitaci\u00f3n \u2018Luis Guillermo Ibarra Ibarra\u2019, Mexico City 14389, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvador","family":"D\u00edaz-Meza","sequence":"additional","affiliation":[{"name":"Hospital General \u2018Dr. Nicol\u00e1s San Juan\u2019, Toluca 50010, State of Mexico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Cabrera-Wrooman","sequence":"additional","affiliation":[{"name":"Laboratory of Connective Tissue, Centro Nacional de Investigaci\u00f3n y Atenci\u00f3n de Quemados, Instituto Nacional de Rehabilitaci\u00f3n \u2018Luis Guillermo Ibarra Ibarra\u2019, Mexico City 14389, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edna Ayerim","family":"Mandujano-Tinoco","sequence":"additional","affiliation":[{"name":"Laboratory of Connective Tissue, Centro Nacional de Investigaci\u00f3n y Atenci\u00f3n de Quemados, Instituto Nacional de Rehabilitaci\u00f3n \u2018Luis Guillermo Ibarra Ibarra\u2019, Mexico City 14389, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa M.","family":"Salgado","sequence":"additional","affiliation":[{"name":"Laboratory of Connective Tissue, Centro Nacional de Investigaci\u00f3n y Atenci\u00f3n de Quemados, Instituto Nacional de Rehabilitaci\u00f3n \u2018Luis Guillermo Ibarra Ibarra\u2019, Mexico City 14389, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8360-6133","authenticated-orcid":false,"given":"Hugo","family":"Tovar","sequence":"additional","affiliation":[{"name":"Computational Genomics Division, National Institute of Genomic Medicine, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8242-7683","authenticated-orcid":false,"given":"Daniel","family":"Mu\u00f1iz-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Hospital General \u2018Dr. Nicol\u00e1s San Juan\u2019, Toluca 50010, State of Mexico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6205-496X","authenticated-orcid":false,"given":"Laura Julieta","family":"Orozco-Casta\u00f1eda","sequence":"additional","affiliation":[{"name":"Hospital General \u2018Dr. Nicol\u00e1s San Juan\u2019, Toluca 50010, State of Mexico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Hern\u00e1ndez-Enr\u00edquez","sequence":"additional","affiliation":[{"name":"Hospital General \u2018Dr. Nicol\u00e1s San Juan\u2019, Toluca 50010, State of Mexico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam Deyanira","family":"Rodr\u00edguez-Pi\u00f1a","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50000, State of Mexico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Sarah\u00ed","family":"Mulia-Soto","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50000, State of Mexico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Meneses-Calder\u00f3n","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50000, State of Mexico, Mexico"},{"name":"Hospital Materno-Perinatal \u2018M\u00f3nica Pretelini S\u00e1enz\u2019, Toluca 50140, State of Mexico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Mondrag\u00f3n-Ter\u00e1n","sequence":"additional","affiliation":[{"name":"CICATA Unidad Morelos, Instituto Polit\u00e9cnico Nacional, Xochitepec 62790, Morelos, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0696-0147","authenticated-orcid":false,"given":"Edgar","family":"Kr\u00f6tzsch","sequence":"additional","affiliation":[{"name":"Laboratory of Connective Tissue, Centro Nacional de Investigaci\u00f3n y Atenci\u00f3n de Quemados, Instituto Nacional de Rehabilitaci\u00f3n \u2018Luis Guillermo Ibarra Ibarra\u2019, Mexico City 14389, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2000285","DOI":"10.2807\/1560-7917.ES.2020.25.11.2000285","article-title":"Control (ECDC) Public Health Emergency Team Rapidly increasing cumulative incidence of coronavirus disease (COVID-19) in the European Union\/European Economic Area and the United Kingdom, 1 January to 15 March 2020","volume":"25","author":"Kinross","year":"2020","journal-title":"Eurosurveillance"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e13209","DOI":"10.1111\/eci.13209","article-title":"The novel Chinese coronavirus (2019nCoV) infections: Challenges for fighting the storm","volume":"50","author":"Bassetti","year":"2020","journal-title":"Eur. 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