Single cell sequencing reveals cellular landscape alterations in the airway mucosa of patients with pulmonary long COVID
Firoozeh V.Gerayeli, Hye Yun Park, Stephen Milne, Xuan Li, Chen Xi Yang, Josie Tuong, Rachel L Eddy, Elizabeth Guinto, Chung Y Cheung, Julia Shun-Wei Yang, Cassie Gilchrist, Dina Yehia, Tara Stach, Tawimas Shaipanich, Jonathon Leipsic, Graeme Koelwyn, Janice M Leung, M.D. Don D Sin
doi:10.1101/2024.02.26.24302674
Single cell profiling shows the infiltration of neutrophils with upregulation of mucin genes in the airway mucosa of patients with pulmonary long COVID, indicating persistent small airway inflammation in pulmonary long COVID.
Author Contributions: FVG, XL,CXY ran the analysis and co-wrote the method section. JT and GK analyzed the IPA analysis and contributed to the method section & discussion section. FVG, HYP, SM,XL,CXY,CYC,JT ,GK and DDS were involved in interpretation of the results. FVG,SM,CYC,EG,RLD,CG,JSWY,TS, DA,TS,JML contributed to the experiment and data acquisition. FVG, HYP and DDS prepared the first draft of the manuscript. All authors contributed to revise the manuscript and approved the final draft of the manuscript.
Supplemental Figures: Supplemental Figure S1A-C
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'group-title': 'Respiratory Medicine',
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'abstract': '<jats:p>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. 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 (PLC), which was defined as '
'persons with new or worsening respiratory symptoms following at least one year from their '
'initial acute 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 not '
'experienced acute COVID-19 (N=9). These participants underwent bronchoscopy from which a '
'single cell suspension was created from bronchial brush samples and then sequenced. A total '
'of 56,906 cells were recovered for the downstream analysis, with 34,840 cells belonging to '
'the PLC group. A dimensionality reduction plot shows a unique cluster of neutrophils in the '
'PLC group (p<.05). Ingenuity Pathway Analysis revealed that neutrophil degranulation '
'pathway was enriched across epithelial cells. Differential gene expression analysis between '
'the PLC and control groups demonstrated upregulation of mucin genes in secretory cell '
'clusters. A single-cell transcriptomic landscape of the small airways shows that the PLC '
'airways harbors a dominant neutrophil cluster and an upregulation in the '
'neutrophil-associated activation signature with increased expression of MUC genes in the '
'secretory cells. Together, they suggest that pulmonary symptoms of long COVID may be driven '
'by chronic small airway inflammation.</jats:p>',
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'title': 'Single cell sequencing reveals cellular landscape alterations in the airway mucosa of patients '
'with pulmonary long COVID',
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