{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T03:51:40Z","timestamp":1793764300114,"version":"4.6.1"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>The COVID-19 pandemic highlighted an urgent need to more efficiently identify patients at highest risk for developing respiratory failure. We investigated whether plasma levels of lung injury biomarkers are associated with progression to respiratory failure among adults hospitalized with COVID-19 pneumonia without respiratory failure at admission.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>This was a nested case-control study of COVID-19 patients enrolled in the Accelerating COVID-19 Therapeutic Interventions and Vaccines-3 (ACTIV-3)\/Therapeutics for Inpatients with COVID-19 (TICO) platform trial who were on less than 20\u2009L\/min supplemental oxygen at enrollment. We compared baseline measurements of lung injury biomarkers between participants who progressed to respiratory failure or died by study day 10 (cases) and matched controls who did not progress to respiratory failure or death. Cases and controls were matched 1:1 on age, baseline oxygen requirement, immunomodulator use, and study arm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting:<\/jats:title>\n                    <jats:p>Hospitals enrolling in the ACTIV-3\/TICO trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients:<\/jats:title>\n                    <jats:p>Four hundred five cases and 405 matched controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions:<\/jats:title>\n                    <jats:p>None.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results:<\/jats:title>\n                    <jats:p>Baseline levels of plasma interleukin (IL)-6, IL-8, IL-18, tumor necrosis factor receptor, angiopoietin-2, soluble receptor for advanced glycation end-products (sRAGE), C-reactive protein (CRP), and surfactant protein D (SPD) were compared between cases and controls using matched logistic regression. Forward variable selection was used to identify biomarkers that were independently associated with progression to respiratory failure or death in a multivariate model. All lung injury biomarkers with the exception of SPD were significantly associated with progression to respiratory failure or death, with sRAGE demonstrating the highest odds ratio (OR) for each doubling of biomarker level (OR, 1.85; 95% CI, 1.61\u20132.12). In multivariate regression analysis, sRAGE, IL-6, and CRP were independently associated with progression, with sRAGE as the biomarker with the strongest association.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Baseline levels of plasma lung injury biomarkers are significantly associated with progression to respiratory failure or death among hospitalized COVID-19 patients without respiratory failure at admission. These findings support the potential utility of measuring lung injury biomarkers in patients hospitalized without respiratory failure and should be tested in more heterogeneous patient groups including non-COVID-19 cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/ccm.0000000000007178","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T14:28:05Z","timestamp":1779805685000},"page":"1979-1989","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Prognostic Value of Lung Injury Biomarkers in Patients Hospitalized With COVID-19 Without Respiratory Failure at Admission"],"prefix":"10.1097","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4254-8475","authenticated-orcid":false,"given":"Jennifer G.","family":"Wilson","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Stanford University School of Medicine, Stanford, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg A.","family":"Grandits","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Science, University of Minnesota School of Public Health, Minneapolis, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Grund","sequence":"additional","affiliation":[{"name":"School of Statistics, University of Minnesota, Minneapolis, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shweta S.","family":"Mistry","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Science, University of Minnesota School of Public Health, Minneapolis, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Leroux","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Ringor","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil R.","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Sciences and Critical Care, University of Colorado School of Medicine, Aurora, CO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel D.","family":"Murray","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Health, Immunity, and Infections, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina E.","family":"Barkauskas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary and Critical Medicine, Duke Medicine, Durham, NC."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel M.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Critical Care, Intermountain Medical Center, Salt Lake City, UT."},{"name":"Department of Medicine, University of Utah, Salt Lake City, UT."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Higgs","sequence":"additional","affiliation":[{"name":"Division of Clinical Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Shaw-Saliba","sequence":"additional","affiliation":[{"name":"Division of Clinical Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Rupert","sequence":"additional","affiliation":[{"name":"Frederick National Laboratory, Frederick, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia L.","family":"Kan","sequence":"additional","affiliation":[{"name":"VA Medical Center and George Washington University School of Medicine and Health Sciences, Washington, DC."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy R.","family":"Beitler","sequence":"additional","affiliation":[{"name":"Aspire Trials Program, Division of Pulmonary, Critical Care and Sleep Medicine, NYU Grossman School of Medicine, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Awan","sequence":"additional","affiliation":[{"name":"VA Medical Center and George Washington University School of Medicine and Health Sciences, Washington, DC."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie L.","family":"Sturgill","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halima","family":"Dawood","sequence":"additional","affiliation":[{"name":"Department of Medicine, Greys Hospital, Pietermaritzburg, South Africa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre C.","family":"Kalil","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, University of Nebraska College of Medicine, Omaha, NE."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Kalomenidis","sequence":"additional","affiliation":[{"name":"Department of Critical Care and Pulmonary Medicine, Medical School, National and Kapodistrian University of Athens, Evangelismos General Hospital, Athens, Greece."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhijit","family":"Duggal","sequence":"additional","affiliation":[{"name":"Department of Critical Care, Integrated Hospital Care Institute, Cleveland Clinic, Cleveland, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah C.","family":"Sasson","sequence":"additional","affiliation":[{"name":"The Kirby Institute, University of New South Wales, Sydney, NSW, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minh Q.","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, University of Central Florida and Department of Internal Medicine, Section Infectious Disease, Orlando VA Healthcare System, Orlando, FL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hien H.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"VA Northern California Health Care System University of California, Davis Health, Sacramento, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens D.","family":"Lundgren","sequence":"additional","affiliation":[{"name":"CHIP (Centre of Excellence for Health, Immunity and Infections), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adit A.","family":"Ginde","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley H.","family":"Self","sequence":"additional","affiliation":[{"name":"Vanderbilt Institute for Clinical and Translational Research and Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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