• Laurence W Busse, J Pedro Teixeira, Christopher L Schaich, Caitlin C Ten Lohuis, Nathan D Nielsen, Jeffrey M Sturek, Lisa H Merck, Wesley H Self, Michael A Puskarich, Akram Khan, Matthew W Semler, Ari Moskowitz, David N Hager, Abhijit Duggal, Todd W Rice, Adit A Ginde, Brian R Tiffany, Nicole M Iovine, Peter Chen, Basmah Safdar, Kevin W Gibbs, Ali Javaheri, Marjolein de Wit, Michelle S Harkins, Meghan M Joly, Sean P Collins, and ACTIV-4 Host Tissue Investigators.
• Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA, USA; Emory Critical Care Center, Emory Healthcare, Atlanta, GA, USA.
• J Crit Care. 2025 Feb 1; 85: 154950154950.

BackgroundPlasma dipeptidyl peptidase-3 (DPP3) and renin levels are associated with organ dysfunction and mortality. However, whether these biomarkers are associated with the subsequent onset of shock in at-risk patients is unknown.MethodsUsing plasma samples collected from participants enrolled in the fourth Accelerating COVID-19 Therapeutic Interventions and Vaccines Host Tissue platform trial, we measured DPP3 and renin in 184 subjects hospitalized with acute hypoxemia from COVID-19 without baseline vasopressor requirement. We calculated the odds ratio of development of shock (defined as the initiation of vasopressor therapy) by Day 28 based on Day 0 DPP3 and renin levels.ResultsSubjects with DPP3 above the median had a significantly higher incidence of vasopressor initiation within 28 days (28.4 % vs. 16.7 %, p = 0.031) and higher 28-day mortality (25.0 % vs. 6.7 %, p < 0.001). After adjusting for covariables, DPP3 above the median was associated with shorter time to vasopressor initiation, greater 28-day mortality, fewer vasopressor-free days, and greater odds of a hypotensive event over 7 days. Significant associations were not observed for renin.ConclusionsIn patients hospitalized with COVID-19 and hypoxemia without baseline hypotension, higher baseline plasma levels of DPP3 but not renin were associated with increased risk of subsequent shock and death.Copyright © 2024 Elsevier Inc. All rights reserved.

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