A specific low-density neutrophil population correlates with hypercoagulation and disease severity in hospitalized COVID-19 patients.
Samantha M Morrissey, Anne E Geller, Xiaoling Hu, David Tieri, Chuanlin Ding, Christopher K Klaes, Elizabeth A Cooke, Matthew R Woeste, Zachary C Martin, Oscar Chen, Sarah E Bush, Huang-Ge Zhang, Rodrigo Cavallazzi, Sean P Clifford, James Chen, Smita Ghare, Shirish S Barve, Lu Cai, Maiying Kong, Eric C Rouchka, Kenneth R McLeish, Silvia M Uriarte, Corey T Watson, Jiapeng Huang, Jun Yan
Author Information
Samantha M Morrissey: Department of Microbiology and Immunology.
Anne E Geller: Department of Microbiology and Immunology.
Xiaoling Hu: Division of Immunotherapy, the Hiram C. Polk, Jr., MD, Department of Surgery, Immuno-Oncology Program, James Graham Brown Cancer Center.
David Tieri: Department of Biochemistry and Molecular Genetics.
Chuanlin Ding: Division of Immunotherapy, the Hiram C. Polk, Jr., MD, Department of Surgery, Immuno-Oncology Program, James Graham Brown Cancer Center.
Christopher K Klaes: Department of Oral Immunology and Infectious Diseases, School of Dentistry.
Elizabeth A Cooke: Department of Anesthesiology and Perioperative Medicine.
Matthew R Woeste: Department of Microbiology and Immunology.
Zachary C Martin: Department of Anesthesiology and Perioperative Medicine.
Oscar Chen: Department of Anesthesiology and Perioperative Medicine.
Sarah E Bush: Department of Anesthesiology and Perioperative Medicine.
Huang-Ge Zhang: Department of Microbiology and Immunology.
Rodrigo Cavallazzi: Division of Pulmonary, Critical Care and Sleep Disorders, Department of Medicine.
Sean P Clifford: Department of Anesthesiology and Perioperative Medicine.
James Chen: Department of Anesthesiology and Perioperative Medicine.
Smita Ghare: University of Louisville Hepatobiology and Toxicology Center, Departments of Medicine and Pharmacology & Toxicology.
Shirish S Barve: University of Louisville Hepatobiology and Toxicology Center, Departments of Medicine and Pharmacology & Toxicology.
Lu Cai: Pediatric Research Institute, Department of Pediatrics.
Maiying Kong: Department of Bioinformatics and Biostatistics.
Eric C Rouchka: Department of Computer Science and Engineering, and.
Kenneth R McLeish: Division of Nephrology and Hypertension, Department of Medicine, University of Louisville, Louisville, Kentucky, USA.
Silvia M Uriarte: Department of Oral Immunology and Infectious Diseases, School of Dentistry.
Corey T Watson: Department of Biochemistry and Molecular Genetics.
Jiapeng Huang: Department of Anesthesiology and Perioperative Medicine.
Jun Yan: Department of Microbiology and Immunology.
SARS coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes a clinical disease called coronavirus disease 2019 (COVID-19). Although most COVID-19 cases are asymptomatic or involve mild upper respiratory tract symptoms, a significant number of patients develop severe or critical disease. Patients with severe COVID-19 commonly present with viral pneumonia that may progress to life-threatening acute respiratory distress syndrome (ARDS). Patients with COVID-19 are also predisposed to venous and arterial thromboses that are associated with a poorer prognosis. The present study identified the emergence of a low-density inflammatory neutrophil (LDN) population expressing intermediate levels of CD16 (CD16Int) in patients with COVID-19. These cells demonstrated proinflammatory gene signatures, activated platelets, spontaneously formed neutrophil extracellular traps, and enhanced phagocytic capacity and cytokine production. Strikingly, CD16Int neutrophils were also the major immune cells within the bronchoalveolar lavage fluid, exhibiting increased CXCR3 but loss of CD44 and CD38 expression. The percentage of circulating CD16Int LDNs was associated with D-dimer, ferritin, and systemic IL-6 and TNF-α levels and changed over time with altered disease status. Our data suggest that the CD16Int LDN subset contributes to COVID-19-associated coagulopathy, systemic inflammation, and ARDS. The frequency of that LDN subset in the circulation could serve as an adjunct clinical marker to monitor disease status and progression.
