Single-cell sequencing reveals cellular landscape alterations in the airway mucosa of patients with pulmonary long COVID.

IF 16.6 1区 医学 Q1 RESPIRATORY SYSTEM
European Respiratory Journal Pub Date : 2024-11-28 Print Date: 2024-11-01 DOI:10.1183/13993003.01947-2023
Firoozeh V Gerayeli, Hye Yun Park, Stephen Milne, Xuan Li, Chen Xi Yang, Josie Tuong, Rachel L Eddy, Seyed Milad Vahedi, Elizabeth Guinto, Chung Y Cheung, Julia S W Yang, Cassie Gilchrist, Dina Yehia, Tara Stach, Hong Dang, Clarus Leung, Tawimas Shaipanich, Jonathon Leipsic, Graeme J Koelwyn, Janice M Leung, Don D Sin
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引用次数: 0

Abstract

Aim: To elucidate the important cellular and molecular drivers of pulmonary long COVID, we generated a single-cell transcriptomic map of the airway mucosa using bronchial brushings from patients with long COVID who reported persistent pulmonary symptoms.

Method: Adults with and without long COVID were recruited from the general community in Greater Vancouver, Canada. The cohort was divided into those with pulmonary long COVID, which was defined as persons with new or worsening respiratory symptoms following ≥12 weeks from their initial acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (n=9); and control subjects defined as SARS-CoV-2 infected persons whose acute respiratory symptoms had fully resolved or individuals who had no history of acute coronavirus disease 2019 (COVID-19) (n=9). These participants underwent bronchoscopy from which a single cell suspension was created from bronchial brush samples and then sequenced.

Results: A total of 56 906 cells were recovered for the downstream analysis, with 34 840 cells belonging to the pulmonary long COVID group, which strikingly showed a unique cluster of neutrophils in the pulmonary long COVID group (p<0.05). Ingenuity Pathway Analysis revealed that the neutrophil degranulation pathway was enriched across epithelial cell clusters. Differential gene expression analysis between the pulmonary long COVID and control groups demonstrated upregulation of inflammatory chemokines and epithelial barrier dysfunction across epithelial cell clusters, as well as over-expression of mucin genes across secretory cell clusters.

Conclusion: A single-cell transcriptomic landscape of the small airways suggest that neutrophils may play a significant role in mediating the chronic small airway inflammation driving pulmonary symptoms of long COVID.

单细胞测序揭示了肺长COVID患者气道粘膜细胞景观的改变。
为了阐明肺部长COVID的重要细胞和分子驱动因素,我们利用报告有持续性肺部症状的长COVID患者的支气管刷片绘制了气道粘膜单细胞转录组图。研究人员从加拿大大温哥华地区的普通社区中招募了患有和未患有长COVID的成年人,并将其分为肺部长COVID(PLC)患者和对照组(N=9),前者的定义是在初次感染急性SARS-CoV-2病毒至少一年后出现新的或恶化的呼吸道症状者;后者的定义是急性呼吸道症状已完全消失的SARS-CoV-2感染者或无急性COVID病史者-19(N=9)。这些受试者接受了支气管镜检查,从支气管刷样本中提取单细胞悬液,然后进行测序。共回收了 56 906 个细胞用于下游分析,其中 34 840 个细胞属于 PLC 组。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
European Respiratory Journal
European Respiratory Journal 医学-呼吸系统
CiteScore
27.50
自引率
3.30%
发文量
345
审稿时长
2-4 weeks
期刊介绍: The European Respiratory Journal (ERJ) is the flagship journal of the European Respiratory Society. It has a current impact factor of 24.9. The journal covers various aspects of adult and paediatric respiratory medicine, including cell biology, epidemiology, immunology, oncology, pathophysiology, imaging, occupational medicine, intensive care, sleep medicine, and thoracic surgery. In addition to original research material, the ERJ publishes editorial commentaries, reviews, short research letters, and correspondence to the editor. The articles are published continuously and collected into 12 monthly issues in two volumes per year.
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