Prognostic Value of Lung Injury Biomarkers in Patients Hospitalized With COVID-19 Without Respiratory Failure at Admission

Year: 2026

Type: article

Abstract: OBJECTIVES: 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. DESIGN: 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 L/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. SETTING: Hospitals enrolling in the ACTIV-3/TICO trials. PATIENTS: Four hundred five cases and 405 matched controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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, 1.61-2.12). In multivariate regression analysis, sRAGE, IL-6, and CRP were independently associated with progression, with sRAGE as the biomarker with the strongest association. CONCLUSIONS: 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.

Source: Critical Care Medicine

DOI: 10.1097/ccm.0000000000007178

Institutions: Stanford Medicine, Stanford University, University of Minnesota, University of California, San Francisco, University of Colorado Anschutz, University of Colorado Denver, Copenhagen University Hospital, Rigshospitalet, Centre of Excellence for Health, Immunity and Infections, Duke University, Duke Medical Center, University of Utah, Intermountain Medical Center, National Institute of Allergy and Infectious Diseases, Frederick National Laboratory for Cancer Research, George Washington University, New York University, University of Kentucky, Grey's Hospital, University of Nebraska Medical Center, National and Kapodistrian University of Athens, Evangelismos Hospital, Cleveland Clinic, UNSW Sydney, Kirby Institute, University of Central Florida, Orlando VA Medical Center, VA Northern California Health Care System, University of California, Davis, University of Copenhagen, Vanderbilt University, Vanderbilt University Medical Center

Language: English

Topic: COVID-19 Clinical Research Studies

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funder: National Heart, Lung, and Blood Institute

Award: ACTIV Integration of Host-targeting Therapies for COVID-19 Administrative Coordinating Center

OpenAlex ID: W7162405778