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However, neutrophil dynamics, functional signatures, and predictive roles in the nasopharynx of coronavirus disease 2019 (COVID\u201019) patients have not yet been elucidated. In this study, we carried out RNA sequencing of nasopharyngeal swabs from a cohort of COVID\u201019 patients with mild, moderate, severe outcomes and healthy donors as controls. Over 32.7% of the differentially expressed genes associated with COVID\u201019 severity were neutrophil\u2010related, including those involved in migration, neutrophil extracellular traps formation, and inflammasome activation. Multicohort single\u2010cell RNA sequencing analysis further confirmed these findings and identified a population of neutrophils expressing Vacuolar\u2010type ATPase (V\u2010ATPase) and the chemokine receptor CXCR4 in the nasopharynx. This population of neutrophils preferentially expressed pro\u2010inflammatory genes relevant to phagosomal maturation as well as local reactive oxygen species and reactive nitrogen species production in the nasopharynx of patients with severe outcomes. A four\u2010gene panel defined as a neutrophil signature associated with COVID\u201019 progression (NSAP) was identified as an early diagnostic predictor of severe COVID\u201019, which potentially distinguished severe patients from mild cases with influenza, respiratory syncytial virus, dengue virus, or hepatitis B virus infection. NSAP is mainly expressed on CXCR4<jats:sup>high<\/jats:sup> neutrophils and exhibits a significant association with the cell fraction of this neutrophil population. This study highlights novel potential therapeutic targets or diagnostic tools for predicting patients at a higher risk of severe outcomes.<\/jats:p>","DOI":"10.1002\/jmv.29328","type":"journal-article","created":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T13:19:06Z","timestamp":1703596746000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Nasopharyngeal neutrophilic\u2010retention signatures could predict disease progression in early SARS\u2010CoV\u20102 infection"],"prefix":"10.1002","volume":"96","author":[{"given":"Furong","family":"Qi","sequence":"first","affiliation":[{"name":"Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital; The Second Affiliated Hospital, School of Medicine Southern University of Science and Technology  Shenzhen Guangdong China"},{"name":"Shenzhen Key Laboratory of Single\u2010Cell Omics Research and Application  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