Transcriptional reprogramming of infiltrating neutrophils drives lung disease in severe COVID-19 despite low viral load.
Blood Adv
; 2022 Nov 18.
Article
in English
| MEDLINE | ID: covidwho-2257907
ABSTRACT
Troubling disparities in COVID-19-associated mortality emerged early, with nearly 70% of deaths confined to Black/African American (AA) patients in some areas. Nevertheless, targeted studies within this vulnerable population are scant. Here, we applied multi-omics 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, led to a 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-1ß, IL-6, and CCL3/4, along with elevated levels of neutrophil elastase and myeloperoxidase, were the hallmarks of a 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 ARDS in a well-defined patient population disproportionally affected by severe COVID-19.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Language:
English
Year:
2022
Document Type:
Article
Affiliation country:
Bloodadvances.2022008834
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