Transcriptional reprogramming of infiltrating neutrophils drives lung pathology in severe COVID-19 despite low viral load.
Blood Adv, 2023/3/14;7(5):778-799.
Eddins DJ[1, 2, 3], Yang J[1], Kosters A[1], Giacalone VD[2, 4], Pechuan-Jorge X[5], Chandler JD[2, 4], Eum J[1, 6], Babcock BR[1], Dobosh BS[2, 4], Hernández MR[7], Abdulkhader F[1], Collins GL[2, 4], Orlova DY[5], Ramonell RP[7], Sanz I[1, 3, 8], Moussion C[5], Eun-Hyung Lee F[1, 3, 7], Tirouvanziam RM[2, 4], Ghosn EEB[1, 2, 3, 6]
Affiliations
PMID: 36399523DOI: 10.1182/bloodadvances.2022008834
Impact factor: 7.637
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. 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.
MeSH terms
Humans; COVID-19; Neutrophils; Interleukin-8; SARS-CoV-2; Viral Load; Lung; Respiratory Distress Syndrome; Membrane Proteins
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