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
{"title":"单细胞测序揭示了肺长COVID患者气道粘膜细胞景观的改变。","authors":"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","doi":"10.1183/13993003.01947-2023","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>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.</p><p><strong>Method: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6000,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602667/pdf/","citationCount":"0","resultStr":"{\"title\":\"Single-cell sequencing reveals cellular landscape alterations in the airway mucosa of patients with pulmonary long COVID.\",\"authors\":\"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\",\"doi\":\"10.1183/13993003.01947-2023\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aim: </strong>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.</p><p><strong>Method: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":12265,\"journal\":{\"name\":\"European Respiratory Journal\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":16.6000,\"publicationDate\":\"2024-11-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602667/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Respiratory Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1183/13993003.01947-2023\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/1 0:00:00\",\"PubModel\":\"Print\",\"JCR\":\"Q1\",\"JCRName\":\"RESPIRATORY SYSTEM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Respiratory Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1183/13993003.01947-2023","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/1 0:00:00","PubModel":"Print","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
Single-cell sequencing reveals cellular landscape alterations in the airway mucosa of patients with pulmonary long COVID.
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.
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.