Transcriptional reprogramming of infiltrating neutrophils drives lung pathology in severe COVID-19 despite low viral load

Autor: Devon J. Eddins, Junkai Yang, Astrid Kosters, Vincent D. Giacalone, Ximo Pechuan-Jorge, Joshua D. Chandler, Jinyoung Eum, Benjamin R. Babcock, Brian S. Dobosh, Mindy R. Hernández, Fathma Abdulkhader, Genoah L. Collins, Darya Y. Orlova, Richard P. Ramonell, Ignacio Sanz, Christine Moussion, F. Eun-Hyung Lee, Rabindra M. Tirouvanziam, Eliver E. B. Ghosn
Rok vydání: 2023
Předmět:
Zdroj: Blood Advances. 7:778-799
ISSN: 2473-9537
2473-9529
DOI: 10.1182/bloodadvances.2022008834
Popis: Troubling disparities in COVID-19–associated mortality emerged early, with nearly 70% of deaths confined to Black/African American (AA) patients in some areas. However, targeted studies on this vulnerable population are scarce. Here, we applied multiomics single-cell analyses of immune profiles from matching airways and blood samples of Black/AA patients during acute SARS-CoV-2 infection. Transcriptional reprogramming of infiltrating IFITM2+/S100A12+ mature neutrophils, likely recruited via the IL-8/CXCR2 axis, leads to persistent and self-sustaining pulmonary neutrophilia with advanced features of acute respiratory distress syndrome (ARDS) despite low viral load in the airways. In addition, exacerbated neutrophil production of IL-8, IL-1β, IL-6, and CCL3/4, along with elevated levels of neutrophil elastase and myeloperoxidase, were the hallmarks of transcriptionally active and pathogenic airway neutrophilia. Although our analysis was limited to Black/AA patients and was not designed as a comparative study across different ethnicities, we present an unprecedented in-depth analysis of the immunopathology that leads to acute respiratory distress syndrome in a well-defined patient population disproportionally affected by severe COVID-19.
Databáze: OpenAIRE
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