• Sarah Louise Murphy, Bente Halvorsen, Jan Cato Holter, Camilla Huse, Anders Tveita, Marius Trøseid, Hedda Hoel, Anders Benjamin Kildal, Aleksander Rygh Holten, Tøri Vigeland Lerum, Ole Henning Skjønsberg, Annika E Michelsen, Trond M Aaløkken, NOR-SOLIDARITY Consortium, The Norwegian SARS-CoV-2 study group investigators, Kristian Tonby, Andreas Lind, Susanne Dudman, Beathe Kiland Granerud, Lars Heggelund, Simen Bøe, Anne Ma Dyrholt-Riise, Pål Aukrust, Andreas Barratt-Due, Thor Ueland, and Tuva Børresdatter Dahl.
• Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
• J. Intern. Med. 2023 Dec 1; 294 (6): 784797784-797.

BackgroundAbnormal 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-19. To further elucidate the role of ECM remodelling and excessive fibrogenesis in severe COVID-19, we examined circulating levels of mediators involved in various aspects of these processes in COVID-19 patients.MethodsSerial blood samples were obtained from two cohorts of hospitalised COVID-19 patients (n = 414). Circulating levels of ECM remodelling mediators were quantified by enzyme immunoassays in samples collected during hospitalisation and at 3-month follow-up. Samples were related to disease severity (respiratory failure and/or treatment at the intensive care unit), 60-day total mortality and pulmonary pathology after 3-months. We also evaluated the direct effect of inactivated SARS-CoV-2 on the release of the different ECM mediators in relevant cell lines.ResultsSeveral of the measured markers were associated with adverse outcomes, notably osteopontin (OPN), S100 calcium-binding protein A12 and YKL-40 were associated with disease severity and mortality. High levels of ECM mediators during hospitalisation were associated with computed tomography thorax pathology after 3-months. 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) in vitro after exposure to inactivated SARS-CoV-2 suggesting a direct link between these mediators and the causal agent of COVID-19.ConclusionOur findings highlight changes to ECM remodelling and particularly a possible role of OPN, S100A12 and YKL-40 in the pathogenesis of severe COVID-19.© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

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