SARS-CoV-2 infection induces hyaluronan production in vitro and hyaluronan levels in COVID-19 patients relate to morbidity and long-term lung impairment: a prospective cohort studyVisa övriga samt affilieringar
2024 (Engelska)Ingår i: mBio, ISSN 2161-2129, E-ISSN 2150-7511, Vol. 15, nr 10, artikel-id e01303-24Artikel i tidskrift (Refereegranskat) Published
Abstract [en]
We previously demonstrated that the lungs of deceased COVID-19 patients were filled with a clear hydrogel consisting of hyaluronan (HA). In this translational study, we investigated the role of HA at all stages of COVID-19 disease to map the consequences of elevated HA on morbidity and identify the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced HA production. A reduced alveolar surface area was observed in the lungs of deceased COVID-19 patients compared to healthy controls, as visualized by a 3D rendering of lung morphology using light-sheet fluorescence microscopy. We confirmed the presence of HA in lung biopsies and found large quantities of proinflammatory fragmented HA. The association of systemic HA in blood plasma and disease severity was assessed in patients with mild (WHO Clinical Progression Scale, WHO-CPS, 1–5) and severe COVID-19 (WHO-CPS, 6–9) during the acute and convalescent phases and related to lung function. We found that systemic levels of HA were high during acute COVID-19 disease, remained elevated during convalescence, and were associated with a reduced diffusion capacity. In vitro 3D-lung models, differentiated from primary human bronchial epithelial cells, were used to study the effects of SARS-CoV-2 infection on HA metabolism, and transcriptomic analyses revealed a dysregulation of HA synthases and hyaluronidases, both contributing to increased HA in apical secretions. Furthermore, corticosteroid treatment reduced the inflammation and downregulated HA synthases. Our findings demonstrate that HA plays a role in COVID-19 morbidity and that sustained elevated HA concentrations may contribute to long-term respiratory impairment.
Ort, förlag, år, upplaga, sidor
American Society for Microbiology, 2024. Vol. 15, nr 10, artikel-id e01303-24
Nyckelord [en]
COVID-19, hyaluronan, hyaluronic acid, SARS-CoV-2, lung impairment, 3D-lung model
Nationell ämneskategori
Infektionsmedicin
Identifikatorer
URN: urn:nbn:se:umu:diva-229944DOI: 10.1128/mbio.01303-24ISI: 001318493400001PubMedID: 39302125Scopus ID: 2-s2.0-85206959059OAI: oai:DiVA.org:umu-229944DiVA, id: diva2:1900134
Forskningsfinansiär
Hjärt-Lungfonden, 20200385Hjärt-Lungfonden, 20200325Hjärt-Lungfonden, 20210078Hjärt-Lungfonden, 20200366Hjärt-Lungfonden, 20210049Kempestiftelserna, JCK-1827Umeå universitet, 978018Umeå universitet, 964781Nyckelfonden, OLL-938628Nyckelfonden, OLL-961416Sjukvårdsregionala forskningsrådet Mellansverige, RFR-968856Sjukvårdsregionala forskningsrådet Mellansverige, RFR-940474Vetenskapsrådet, 2020-06235Vetenskapsrådet, 2016-06514Vetenskapsrådet, 2021-06602Åke Wibergs Stiftelse, M22-0106Magnus Bergvalls Stiftelse, 2022-1862024-09-232024-09-232024-10-28Bibliografiskt granskad