A neutrophil activation signature predicts critical illness and mortality in COVID-19
Open Access
- 26 February 2021
- journal article
- research article
- Published by American Society of Hematology in Blood Advances
- Vol. 5 (5), 1164-1177
- https://doi.org/10.1182/bloodadvances.2020003568
Abstract
Pathologic immune hyperactivation is emerging as a key feature of critical illness in COVID-19, but the mechanisms involved remain poorly understood. We carried out proteomic profiling of plasma from cross-sectional and longitudinal cohorts of hospitalized patients with COVID-19 and analyzed clinical data from our health system database of more than 3300 patients. Using a machine learning algorithm, we identified a prominent signature of neutrophil activation, including resistin, lipocalin-2, hepatocyte growth factor, interleukin-8, and granulocyte colony-stimulating factor, which were the strongest predictors of critical illness. Evidence of neutrophil activation was present on the first day of hospitalization in patients who would only later require transfer to the intensive care unit, thus preceding the onset of critical illness and predicting increased mortality. In the health system database, early elevations in developing and mature neutrophil counts also predicted higher mortality rates. Altogether, these data suggest a central role for neutrophil activation in the pathogenesis of severe COVID-19 and identify molecular markers that distinguish patients at risk of future clinical decompensation.Keywords
This publication has 44 references indexed in Scilit:
- Disease Tolerance as a Defense StrategyScience, 2012
- Resistin: functional roles and therapeutic considerations for cardiovascular diseaseBritish Journal of Pharmacology, 2012
- Early Elevation of Matrix Metalloproteinase-8 and -9 in Pediatric ARDS Is Associated with an Increased Risk of Prolonged Mechanical VentilationPLOS ONE, 2011
- Excessive Neutrophils and Neutrophil Extracellular Traps Contribute to Acute Lung Injury of Influenza PneumonitisThe American Journal of Pathology, 2011
- Resistin induces expression of proinflammatory cytokines and chemokines in human articular chondrocytes via transcription and messenger RNA stabilizationArthritis & Rheumatism, 2010
- Resistin is stored in neutrophil granules being released upon challenge with inflammatory stimuliBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2009
- Subendothelial infiltration of neutrophil granulocytes and liberation of matrix-destabilizing enzymes in an experimental model of human neo-intimaThrombosis and Haemostasis, 2008
- Mechanisms of Degranulation in NeutrophilsAllergy, Asthma & Clinical Immunology, 2006
- Identification of murine and human XCP1 genes as C/EBP-ε-dependent members of FIZZ/Resistin gene familyOncogene, 2004
- Molecular Cloning and Expression of a cDNA Encoding NGAL: A Lipocalin Expressed in Human NeutrophilsBiochemical and Biophysical Research Communications, 1994