{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T15:11:33Z","timestamp":1781277093153,"version":"3.54.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The National Program for Clinical Therapy Research in the Specialist Health Service.","award":["Grant no. 2020201"],"award-info":[{"award-number":["Grant no. 2020201"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The association between pulmonary sequelae and markers of disease severity, as well as pro-fibrotic mediators, were studied in 108 patients 3\u00a0months after hospital admission for COVID-19. The COPD assessment test (CAT-score), spirometry, diffusion capacity of the lungs (DL<jats:sub>CO<\/jats:sub>), and chest-CT were performed at 23 Norwegian hospitals included in the NOR-SOLIDARITY trial, an open-labelled, randomised clinical trial, investigating the efficacy of remdesivir and hydroxychloroquine (HCQ). Thirty-eight percent had a CAT-score\u2009\u2265\u200910. DL<jats:sub>CO<\/jats:sub> was below the lower limit of normal in 29.6%. Ground-glass opacities were present in 39.8% on chest-CT, parenchymal bands were found in 41.7%. At admission, low pO<jats:sub>2<\/jats:sub>\/F<jats:sub>i<\/jats:sub>O<jats:sub>2<\/jats:sub> ratio, ICU treatment, high viral load, and low antibody levels, were predictors of a poorer pulmonary outcome after 3\u00a0months. High levels of matrix metalloproteinase (MMP)-9 during hospitalisation and at 3\u00a0months were associated with persistent CT-findings. Except for a negative effect of remdesivir on CAT-score, we found no effect of remdesivir or HCQ on long-term pulmonary outcomes. Three months after hospital admission for COVID-19, a high prevalence of respiratory symptoms, reduced DL<jats:sub>CO<\/jats:sub>, and persistent CT-findings was observed. Low pO<jats:sub>2<\/jats:sub>\/F<jats:sub>i<\/jats:sub>O<jats:sub>2<\/jats:sub> ratio, ICU-admission, high viral load, low antibody levels, and high levels of MMP-9 were associated with a worse pulmonary outcome.<\/jats:p>","DOI":"10.1038\/s41598-021-02547-x","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T11:04:42Z","timestamp":1638356682000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Persistent pulmonary pathology after COVID-19 is associated with high viral load, weak antibody response, and high levels of matrix metalloproteinase-9"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8326-9993","authenticated-orcid":false,"given":"T\u00f8ri Vigeland","family":"Lerum","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas Nyboe","family":"Maltzahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e5l","family":"Aukrust","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Tr\u00f8seid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina Nezvalova","family":"Henriksen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trine","family":"K\u00e5sine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4009-4032","authenticated-orcid":false,"given":"Anne-Ma","family":"Dyrhol-Riise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitte","family":"Stiksrud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette","family":"Haugli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f8rn","family":"Blomberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e5rd Reiakvam","family":"Kittang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asgeir","family":"Johannessen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raisa","family":"Hannula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad","family":"Aballi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders Benjamin","family":"Kildal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ragnhild","family":"Eiken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuva B\u00f8rresdatter","family":"Dahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fridtjof","family":"Lund-Johansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jezabel Rivero","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carin","family":"Meltzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Einvik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thor","family":"Ueland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge Christoffer","family":"Olsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"NOR-SOLIDARITY Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank Olav","family":"Pettersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander Rygh","family":"Holten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Tonby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dag Henrik","family":"Reikvam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjerstin","family":"R\u00f8stad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Synne","family":"Jenum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liv","family":"Hesstvedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline Brenno","family":"Vaage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anette","family":"Kolderup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trung","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Terje","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Holberg-Petersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simreen Kaur","family":"Johal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c5se","family":"Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Tveita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gernot","family":"Ernst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Heggelund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Thoresen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl Erik","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dag Arne Lihaug","family":"Hoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy Bj\u00f8rkholt","family":"Olsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ane-Krisitne","family":"Finbr\u00e5ten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hedda","family":"Hoel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Mathiessen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif Erik","family":"Vinge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena Bugge","family":"Nordberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravinea","family":"Manotheepan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grethe-Elisabeth","family":"Stenvik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Schmidt","family":"Rasmussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth Foseide","family":"Thorkildsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Mielnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan Ai Kieu","family":"Le","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl Magnus","family":"Ystr\u00f8m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard Alexander","family":"Molvik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina Vibeche","family":"Skei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olav","family":"Dalgard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f8rn","family":"\u00c5sheim-Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Marie","family":"Halstensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorunn","family":"Brynhildsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waleed","family":"Ghanima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vegard","family":"Skogen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisine Greve Isdahl","family":"Mohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reidar","family":"Kv\u00e5le","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Langeland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lise Tuset","family":"Gustad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars M\u00f8lgaard","family":"Saxhaug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathrine","family":"Fladeby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Dudman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Steffensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Barratt-Due","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trond Mogens","family":"Aal\u00f8kken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole Henning","family":"Skj\u00f8nsberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,1]]},"reference":[{"key":"2547_CR1","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","volume":"579","author":"P Zhou","year":"2020","unstructured":"Zhou, P. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270\u2013273. https:\/\/doi.org\/10.1038\/s41586-020-2012-7 (2020).","journal-title":"Nature"},{"key":"2547_CR2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.03448-2020","author":"TV Lerum","year":"2020","unstructured":"Lerum, T. V. et al. Dyspnoea, lung function and CT findings 3 months after hospital admission for COVID-19. Eur. Respir. J. https:\/\/doi.org\/10.1183\/13993003.03448-2020 (2020).","journal-title":"Eur. Respir. J."},{"key":"2547_CR3","doi-asserted-by":"publisher","first-page":"2003690","DOI":"10.1183\/13993003.03690-2020","volume":"57","author":"SA Guler","year":"2021","unstructured":"Guler, S. A. et al. Pulmonary function and radiological features four months after COVID-19: First results from the national prospective observational Swiss COVID-19 lung study. Eur. Respir. J. 57, 2003690. https:\/\/doi.org\/10.1183\/13993003.03690-2020 (2021).","journal-title":"Eur. Respir. J."},{"key":"2547_CR4","doi-asserted-by":"publisher","first-page":"110267","DOI":"10.1016\/j.biopha.2020.110267","volume":"128","author":"R Salvi","year":"2020","unstructured":"Salvi, R. & Patankar, P. Emerging pharmacotherapies for COVID-19. Biomed. Pharmacother. 128, 110267. https:\/\/doi.org\/10.1016\/j.biopha.2020.110267 (2020).","journal-title":"Biomed. Pharmacother."},{"key":"2547_CR5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2023184","author":"WHO Solidarity Trial Consortium","year":"2020","unstructured":"WHO Solidarity Trial Consortium. Repurposed antiviral drugs for covid-19\u2014Interim WHO solidarity trial results. N. Engl. J. Med. https:\/\/doi.org\/10.1056\/NEJMoa2023184 (2020).","journal-title":"N. Engl. J. Med."},{"key":"2547_CR6","doi-asserted-by":"publisher","DOI":"10.7326\/M21-0653","author":"A Barratt-Due","year":"2021","unstructured":"Barratt-Due, A. et al. Evaluation of the effects of remdesivir and hydroxychloroquine on viral clearance in COVID-19: A randomized trial. Ann. Intern. Med. https:\/\/doi.org\/10.7326\/M21-0653 (2021).","journal-title":"Ann. Intern. Med."},{"key":"2547_CR7","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.antiviral.2017.03.022","volume":"143","author":"T Venkataraman","year":"2017","unstructured":"Venkataraman, T. & Frieman, M. B. The role of epidermal growth factor receptor (EGFR) signaling in SARS coronavirus-induced pulmonary fibrosis. Antiviral Res. 143, 142\u2013150. https:\/\/doi.org\/10.1016\/j.antiviral.2017.03.022 (2017).","journal-title":"Antiviral Res."},{"key":"2547_CR8","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1183\/09031936.00032111","volume":"38","author":"A Davey","year":"2011","unstructured":"Davey, A., McAuley, D. F. & O\u2019Kane, C. M. Matrix metalloproteinases in acute lung injury: Mediators of injury and drivers of repair. Eur. Respir. J. 38, 959\u2013970. https:\/\/doi.org\/10.1183\/09031936.00032111 (2011).","journal-title":"Eur. Respir. J."},{"key":"2547_CR9","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.rmed.2017.08.021","volume":"131","author":"K Ikeda","year":"2017","unstructured":"Ikeda, K. et al. Serum surfactant protein D predicts the outcome of patients with idiopathic pulmonary fibrosis treated with pirfenidone. Respir. Med. 131, 184\u2013191. https:\/\/doi.org\/10.1016\/j.rmed.2017.08.021 (2017).","journal-title":"Respir. Med."},{"key":"2547_CR10","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/s00408-009-9223-x","volume":"188","author":"M Ando","year":"2010","unstructured":"Ando, M. et al. Significance of serum vascular endothelial growth factor level in patients with idiopathic pulmonary fibrosis. Lung 188, 247\u2013252. https:\/\/doi.org\/10.1007\/s00408-009-9223-x (2010).","journal-title":"Lung"},{"key":"2547_CR11","doi-asserted-by":"publisher","first-page":"e41","DOI":"10.1016\/j.jinf.2020.06.061","volume":"81","author":"T Ueland","year":"2020","unstructured":"Ueland, T. et al. Distinct and early increase in circulating MMP-9 in COVID-19 patients with respiratory failure. J. Infect. 81, e41\u2013e43. https:\/\/doi.org\/10.1016\/j.jinf.2020.06.061 (2020).","journal-title":"J. Infect."},{"key":"2547_CR12","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1007\/s00408-020-00393-8","volume":"198","author":"B Kerget","year":"2020","unstructured":"Kerget, B. et al. Are serum interleukin 6 and surfactant protein D levels associated with the clinical course of COVID-19? Lung 198, 777\u2013784. https:\/\/doi.org\/10.1007\/s00408-020-00393-8 (2020).","journal-title":"Lung"},{"key":"2547_CR13","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1097\/CCM.0000000000002514","volume":"45","author":"SM Brown","year":"2017","unstructured":"Brown, S. M. et al. Nonlinear imputation of PaO2\/FIO2 from SpO2\/FIO2 among mechanically ventilated patients in the ICU: A prospective. Observational study. Crit. Care Med. 45, 1317\u20131324. https:\/\/doi.org\/10.1097\/CCM.0000000000002514 (2017).","journal-title":"Crit. Care Med."},{"key":"2547_CR14","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1183\/09031936.00102509","volume":"34","author":"PW Jones","year":"2009","unstructured":"Jones, P. W. et al. Development and first validation of the COPD assessment test. Eur. Respir. J. 34, 648\u2013654. https:\/\/doi.org\/10.1183\/09031936.00102509 (2009).","journal-title":"Eur. Respir. J."},{"key":"2547_CR15","first-page":"22","volume":"11","author":"H Ghobadi","year":"2012","unstructured":"Ghobadi, H., Ahari, S. S., Kameli, A. & Lari, S. M. The relationship between COPD assessment test (CAT) scores and severity of airflow obstruction in stable COPD patients. Tanaffos 11, 22\u201326 (2012).","journal-title":"Tanaffos"},{"key":"2547_CR16","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00016-2016","author":"BL Graham","year":"2017","unstructured":"Graham, B. L. et al. 2017 ERS\/ATS standards for single-breath carbon monoxide uptake in the lung. Eur. Respir. J. https:\/\/doi.org\/10.1183\/13993003.00016-2016 (2017).","journal-title":"Eur. Respir. J."},{"key":"2547_CR17","doi-asserted-by":"publisher","first-page":"e70","DOI":"10.1164\/rccm.201908-1590ST","volume":"200","author":"BL Graham","year":"2019","unstructured":"Graham, B. L. et al. Standardization of spirometry 2019 update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am. J. Respir. Crit. Care Med. 200, e70\u2013e88. https:\/\/doi.org\/10.1164\/rccm.201908-1590ST (2019).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2547_CR18","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1183\/09031936.00080312","volume":"40","author":"PH Quanjer","year":"2012","unstructured":"Quanjer, P. H. et al. Multi-ethnic reference values for spirometry for the 3\u201395-yr age range: The global lung function 2012 equations. Eur. Respir. J. 40, 1324\u20131343. https:\/\/doi.org\/10.1183\/09031936.00080312 (2012).","journal-title":"Eur. Respir. J."},{"key":"2547_CR19","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00010-2017","author":"S Stanojevic","year":"2017","unstructured":"Stanojevic, S. et al. Official ERS technical standards: Global lung function initiative reference values for the carbon monoxide transfer factor for Caucasians. Eur. Respir. J. https:\/\/doi.org\/10.1183\/13993003.00010-2017 (2017).","journal-title":"Eur. Respir. J."},{"key":"2547_CR20","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1148\/radiol.2462070712","volume":"246","author":"DM Hansell","year":"2008","unstructured":"Hansell, D. M. et al. Fleischner society: Glossary of terms for thoracic imaging. Radiology 246, 697\u2013722. https:\/\/doi.org\/10.1148\/radiol.2462070712 (2008).","journal-title":"Radiology"},{"key":"2547_CR21","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/j.rmed.2015.05.008","volume":"109","author":"V Soyseth","year":"2015","unstructured":"Soyseth, V. et al. Diagnosis of biopsy verified usual interstitial pneumonia by computed tomography. Respir. Med. 109, 897\u2013903. https:\/\/doi.org\/10.1016\/j.rmed.2015.05.008 (2015).","journal-title":"Respir. Med."},{"key":"2547_CR22","doi-asserted-by":"publisher","first-page":"2052","DOI":"10.1001\/jama.2020.6775","volume":"323","author":"S Richardson","year":"2020","unstructured":"Richardson, S. et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 323, 2052\u20132059. https:\/\/doi.org\/10.1001\/jama.2020.6775 (2020).","journal-title":"JAMA"},{"key":"2547_CR23","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1093\/cid\/ciaa344","volume":"71","author":"J Zhao","year":"2020","unstructured":"Zhao, J. et al. Antibody responses to SARS-CoV-2 in patients with novel coronavirus disease 2019. Clin. Infect. Dis. 71, 2027\u20132034. https:\/\/doi.org\/10.1093\/cid\/ciaa344 (2020).","journal-title":"Clin. Infect. Dis."},{"key":"2547_CR24","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","volume":"395","author":"F Zhou","year":"2020","unstructured":"Zhou, F. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 395, 1054\u20131062. https:\/\/doi.org\/10.1016\/S0140-6736(20)30566-3 (2020).","journal-title":"Lancet"},{"key":"2547_CR25","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1016\/S0140-6736(20)31189-2","volume":"395","author":"MJ Cummings","year":"2020","unstructured":"Cummings, M. J. et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: A prospective cohort study. Lancet 395, 1763\u20131770. https:\/\/doi.org\/10.1016\/S0140-6736(20)31189-2 (2020).","journal-title":"Lancet"},{"key":"2547_CR26","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/s41577-020-0311-8","volume":"20","author":"MZ Tay","year":"2020","unstructured":"Tay, M. Z., Poh, C. M., Renia, L., MacAry, P. A. & Ng, L. F. P. The trinity of COVID-19: Immunity, inflammation and intervention. Nat. Rev. Immunol. 20, 363\u2013374. https:\/\/doi.org\/10.1038\/s41577-020-0311-8 (2020).","journal-title":"Nat. Rev. Immunol."},{"key":"2547_CR27","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/s41392-020-0148-4","volume":"5","author":"L Tan","year":"2020","unstructured":"Tan, L. et al. Lymphopenia predicts disease severity of COVID-19: A descriptive and predictive study. Signal Transduct. Target Ther. 5, 33. https:\/\/doi.org\/10.1038\/s41392-020-0148-4 (2020).","journal-title":"Signal Transduct. Target Ther."},{"key":"2547_CR28","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13377","author":"T Kasine","year":"2021","unstructured":"Kasine, T. et al. Neutrophil count predicts clinical outcome in hospitalized covid-19 patients: Results from the NOR-Solidarity trial. J. Intern. Med. https:\/\/doi.org\/10.1111\/joim.13377 (2021).","journal-title":"J. Intern. Med."},{"key":"2547_CR29","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/infdis\/jiaa632","volume":"223","author":"A Yilmaz","year":"2021","unstructured":"Yilmaz, A. et al. Upper respiratory tract levels of severe acute respiratory syndrome coronavirus 2 RNA and duration of viral RNA shedding do not differ between patients with mild and severe\/critical coronavirus disease 2019. J. Infect. Dis. 223, 15\u201318. https:\/\/doi.org\/10.1093\/infdis\/jiaa632 (2021).","journal-title":"J. Infect. Dis."},{"key":"2547_CR30","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1002\/jmv.26389","volume":"93","author":"RK Reddy","year":"2021","unstructured":"Reddy, R. K. et al. The effect of smoking on COVID-19 severity: A systematic review and meta-analysis. J. Med. Virol. 93, 1045\u20131056. https:\/\/doi.org\/10.1002\/jmv.26389 (2021).","journal-title":"J. Med. Virol."},{"key":"2547_CR31","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1152\/ajplung.90578.2008","volume":"296","author":"PD Vermeer","year":"2009","unstructured":"Vermeer, P. D. et al. MMP9 modulates tight junction integrity and cell viability in human airway epithelia. Am. J. Physiol. Lung Cell Mol. Physiol. 296, 751\u2013762. https:\/\/doi.org\/10.1152\/ajplung.90578.2008 (2009).","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"2547_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-7643-8585-9_1","volume-title":"Matrix Metalloproteinases in Tissue Remodelling and Inflammation","author":"S Wong","year":"2008","unstructured":"Wong, S., Birrell, M. A. & Belvisi, M. G. Matrix Metalloproteinases in Tissue Remodelling and Inflammation 1\u201320 (Springer, 2008)."},{"key":"2547_CR33","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21249739","author":"GA Cabral-Pacheco","year":"2020","unstructured":"Cabral-Pacheco, G. A. et al. The roles of matrix metalloproteinases and their inhibitors in human diseases. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms21249739 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"2547_CR34","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1136\/thx.2005.051979","volume":"61","author":"PT Elkington","year":"2006","unstructured":"Elkington, P. T. & Friedland, J. S. Matrix metalloproteinases in destructive pulmonary pathology. Thorax 61, 259\u2013266. https:\/\/doi.org\/10.1136\/thx.2005.051979 (2006).","journal-title":"Thorax"},{"key":"2547_CR35","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1164\/rccm.201910-1977OC","volume":"203","author":"MS Espindola","year":"2021","unstructured":"Espindola, M. S. et al. Differential responses to targeting matrix metalloproteinase 9 in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 203, 458\u2013470. https:\/\/doi.org\/10.1164\/rccm.201910-1977OC (2021).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2547_CR36","doi-asserted-by":"publisher","first-page":"100052","DOI":"10.1016\/j.medidd.2020.100052","volume":"7","author":"B Solun","year":"2020","unstructured":"Solun, B. & Shoenfeld, Y. Inhibition of metalloproteinases in therapy for severe lung injury due to COVID-19. Med. Drug Discov. 7, 100052. https:\/\/doi.org\/10.1016\/j.medidd.2020.100052 (2020).","journal-title":"Med. Drug Discov."},{"key":"2547_CR37","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1136\/thx.2005.040204","volume":"61","author":"AR Medford","year":"2006","unstructured":"Medford, A. R. & Millar, A. B. Vascular endothelial growth factor (VEGF) in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): Paradox or paradigm? Thorax 61, 621\u2013626. https:\/\/doi.org\/10.1136\/thx.2005.040204 (2006).","journal-title":"Thorax"},{"key":"2547_CR38","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1183\/09031936.00149614","volume":"45","author":"F Grimminger","year":"2015","unstructured":"Grimminger, F., Gunther, A. & Vancheri, C. The role of tyrosine kinases in the pathogenesis of idiopathic pulmonary fibrosis. Eur. Respir. J. 45, 1426\u20131433. https:\/\/doi.org\/10.1183\/09031936.00149614 (2015).","journal-title":"Eur. Respir. J."},{"key":"2547_CR39","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1093\/infdis\/jiab167","volume":"224","author":"F Syed","year":"2021","unstructured":"Syed, F. et al. Excessive matrix metalloproteinase-1 and hyperactivation of endothelial cells occurred in COVID-19 patients and were associated with the severity of COVID-19. J. Infect. Dis. 224, 60\u201369. https:\/\/doi.org\/10.1093\/infdis\/jiab167 (2021).","journal-title":"J. Infect. Dis."},{"key":"2547_CR40","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1093\/infdis\/jiab347","volume":"224","author":"MK Kristensen","year":"2021","unstructured":"Kristensen, M. K., Plovsing, R. R., Berg, R. M. G., Krogh-Madsen, R. & Ronit, A. Cell adhesion molecules and vascular endothelial growth factor at the systemic and alveolar level in coronavirus disease 2019 acute respiratory distress syndrome. J. Infect. Dis. 224, 1101\u20131103. https:\/\/doi.org\/10.1093\/infdis\/jiab347 (2021).","journal-title":"J. Infect. Dis."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-02547-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-02547-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-02547-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T18:00:21Z","timestamp":1670090421000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-02547-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,1]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["2547"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-02547-x","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,1]]},"assertion":[{"value":"12 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Gunnar Einvik reports grants from Boehringer Ingelheim in relation to previous work, unrelated to the submitted report. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"23205"}}