{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:46:17Z","timestamp":1789015577922,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006095","name":"Helse S\u00f8r-\u00d8st RHF","doi-asserted-by":"publisher","award":["2021071"],"award-info":[{"award-number":["2021071"]}],"id":[{"id":"10.13039\/501100006095","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Abnormal remodelling of the extracellular matrix (ECM) has generally been linked to pulmonary inflammation and fibrosis and may also play a role in the pathogenesis of severe COVID\u201019. To further elucidate the role of ECM remodelling and excessive fibrogenesis in severe COVID\u201019, we examined circulating levels of mediators involved in various aspects of these processes in COVID\u201019 patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serial blood samples were obtained from two cohorts of hospitalised COVID\u201019 patients (<jats:italic>n<\/jats:italic>\u00a0=\u00a0414). Circulating levels of ECM remodelling mediators were quantified by enzyme immunoassays in samples collected during hospitalisation and at 3\u2010month follow\u2010up. Samples were related to disease severity (respiratory failure and\/or treatment at the intensive care unit), 60\u2010day total mortality and pulmonary pathology after 3\u2010months. We also evaluated the direct effect of inactivated SARS\u2010CoV\u20102 on the release of the different ECM mediators in relevant cell lines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Several of the measured markers were associated with adverse outcomes, notably osteopontin (OPN), S100 calcium\u2010binding protein A12 and YKL\u201040 were associated with disease severity and mortality. High levels of ECM mediators during hospitalisation were associated with computed tomography thorax pathology after 3\u2010months. Some markers (i.e. growth differential factor 15, galectin 3 and matrix metalloproteinase 9) were released from various relevant cell lines (i.e. macrophages and lung cell lines) <jats:italic>in vitro<\/jats:italic> after exposure to inactivated SARS\u2010CoV\u20102 suggesting a direct link between these mediators and the causal agent of COVID\u201019.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings highlight changes to ECM remodelling and particularly a possible role of OPN, S100A12 and YKL\u201040 in the pathogenesis of severe COVID\u201019.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.13725","type":"journal-article","created":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T06:43:18Z","timestamp":1695019398000},"page":"784-797","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Circulating markers of extracellular matrix remodelling in severe COVID\u201019 patients"],"prefix":"10.1111","volume":"294","author":[{"given":"Sarah Louise","family":"Murphy","sequence":"first","affiliation":[{"name":"Research Institute of Internal Medicine Oslo University Hospital Rikshospitalet  Oslo Norway"},{"name":"Faculty of Medicine Institute of Clinical Medicine University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bente","family":"Halvorsen","sequence":"additional","affiliation":[{"name":"Research Institute of Internal Medicine Oslo University Hospital Rikshospitalet  Oslo Norway"},{"name":"Faculty of Medicine Institute of Clinical Medicine University of Oslo  Oslo Norway"},{"name":"Department of Medicine Division of Cardiovascular Medicine Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Cato","family":"Holter","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Institute of Clinical Medicine 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