Persistent alveolar bronchiolization, interstitial fibrosis and impaired lung function post-exercise are features of long-COVID in SARS-CoV-2-Delta variant infected aged hamsters

Persistent alveolar bronchiolization, interstitial fibrosis and impaired lung function post-exercise are features of long-COVID in SARS-CoV-2-Delta variant infected aged hamsters | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Persistent alveolar bronchiolization, interstitial fibrosis and impaired lung function post-exercise are features of long-COVID in SARS-CoV-2-Delta variant infected aged hamsters Wolfgang Baumgärtner, Laura Heydemann, Małgorzata Ciurkiewicz, and 21 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4681343/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Feb, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Long-term consequences of SARS-CoV-2 infection affect the life quality of millions of people and pose a heavy burden on the public health sector. The underlying causes, pathomechanisms and morphological correlates are still largely unknown and further research in appropriate animal models is needed. The goal of the study was to characterize the trajectory of lung regeneration over a period of 112 days in the hamster model by combining morphological, transcriptome analysis and functional readouts. We demonstrate that in the acute phase, SARS-CoV-2 Delta-infected, male, aged hamsters show a severe impairment of lung function in a resting state. In the chronic phase of the disease, similar impairments are appreciable until 7 weeks post infection only after exercise on a rodent treadmill. The hamster model recapitulates chronic pulmonary fibrotic changes observed in many patients with respiratory long COVID, but does not show extra-pulmonary long term lesions. We show that sub-pleural and interstitial pulmonary fibrosis as well as alveolar bronchiolization persist until 112 dpi. Interestingly, CK8+ alveolar differentiation intermediate (ADI) cells are becoming less prominent in the alveolar proliferation areas from 28 dpi on. Instead, CK14+ airway basal cells and SCGB1A1+ club cells, expressing cell proliferation markers, mainly populate alveolar bronchiolization areas at later time-points. We postulate that pulmonary fibrosis and SCGB1A1+ club cell rich areas of alveolar bronchiolization represent potential risk factors for other diseases in long-COVID survivors. Biological sciences/Microbiology/Virology/SARS-CoV-2 Biological sciences/Physiology/Respiration Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryinformationHeydemannetal.docx nrreportingsummary.pdf Reporting Summary SupplementaryData1.xlsx Supplementary Data 1 SupplementaryData2.xlsx Supplementary Data 2 SupplementaryData3.xlsx Supplementary Data 3 SupplementaryData4.xlsx Supplementary Data 4 SupplementaryData5.xlsx Supplementary Data 5 SupplementaryData6.xlsx Supplementary Data 6 Cite Share Download PDF Status: Published Journal Publication published 28 Feb, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4681343","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":325677894,"identity":"e27a74c1-6959-496c-855c-21626318fc38","order_by":0,"name":"Wolfgang 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