Nasopharyngeal neutrophilic-retention signatures could predict disease progression in early SARS-CoV-2 infection

Qi，Furong1,2; Cao，Yingyin1; Shen，Yunyun1; Wang，Haiyan1; Li，Dapeng1; Yang，Qianting1; Li，Zhiyan3; Zhang，Zheng1,2

2024

10.1002/jmv.29328

Journal of Medical Virology   影响因子和分区

0146-6615

1096-9071

The nasopharynx is the initial site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and neutrophils play a critical role in preventing viral transmission into the lower airways or lungs during the early phases of infection. However, neutrophil dynamics, functional signatures, and predictive roles in the nasopharynx of coronavirus disease 2019 (COVID-19) patients have not yet been elucidated. In this study, we carried out RNA sequencing of nasopharyngeal swabs from a cohort of COVID-19 patients with mild, moderate, severe outcomes and healthy donors as controls. Over 32.7% of the differentially expressed genes associated with COVID-19 severity were neutrophil-related, including those involved in migration, neutrophil extracellular traps formation, and inflammasome activation. Multicohort single-cell RNA sequencing analysis further confirmed these findings and identified a population of neutrophils expressing Vacuolar-type ATPase (V-ATPase) and the chemokine receptor CXCR4 in the nasopharynx. This population of neutrophils preferentially expressed pro-inflammatory 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-gene panel defined as a neutrophil signature associated with COVID-19 progression (NSAP) was identified as an early diagnostic predictor of severe COVID-19, 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 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.

COVID-19 nasopharynx neutrophils predictor severity

SCI

英语

第一 ; 通讯

MICROBIOLOGY

2-s2.0-85181176645

Scopus

1.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
2.Shenzhen Key Laboratory of Single-Cell Omics Research and Application,Shenzhen,China
3.Department of Ultrasonography,Shenzhen Third People's Hospital,The Second Affiliated Hospital,Southern University of Science and Technology,Shenzhen,China

Qi，Furong,Cao，Yingyin,Shen，Yunyun,et al. Nasopharyngeal neutrophilic-retention signatures could predict disease progression in early SARS-CoV-2 infection[J]. Journal of Medical Virology,2024,96(1).

Qi，Furong.,Cao，Yingyin.,Shen，Yunyun.,Wang，Haiyan.,Li，Dapeng.,...&Zhang，Zheng.(2024).Nasopharyngeal neutrophilic-retention signatures could predict disease progression in early SARS-CoV-2 infection.Journal of Medical Virology,96(1).

Qi，Furong,et al."Nasopharyngeal neutrophilic-retention signatures could predict disease progression in early SARS-CoV-2 infection".Journal of Medical Virology 96.1(2024).