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SARS-CoV-2 activates lung epithelial cell proinflammatory signaling and leads to immune dysregulation in COVID-19 patients.
Chen, Huarong; Liu, Weixin; Wang, Yifei; Liu, Dabin; Zhao, Liuyang; Yu, Jun.
  • Chen H; Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong; Department of Anaesthesia and Intensive Care and Peter Hu
  • Liu W; Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong.
  • Wang Y; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
  • Liu D; Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong.
  • Zhao L; Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong.
  • Yu J; Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong.
EBioMedicine ; 70: 103500, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1322074
ABSTRACT

BACKGROUND:

The outbreak of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection has become a global health emergency. We aim to decipher SARS-CoV-2 infected cell types, the consequent host immune response and their interplay in lung of COVID-19 patients.

METHODS:

We analyzed single-cell RNA sequencing (scRNA-seq) data of bronchoalveolar lavage fluid (BALF) samples from 10 healthy donors, 6 severe COVID-19 patients and 3 mild recovered patients. The expressions of SARS-CoV-2 receptors (ACE2 and TMPRSS2) were examined among different cell types. The immune cells infiltration patterns, their expression profiles, and interplays between immune cells and SARS-CoV-2 target cells were further investigated.

FINDINGS:

Compared to healthy controls, ACE2 and TMPRSS2 expressions were significantly higher in lung epithelial cells of COVID-19 patients, in particular club and ciliated cells. SARS-CoV-2 activated pro-inflammatory genes and interferon/cytokine signaling in these cells. In severe COVID-19 patients, significantly higher neutrophil, but lower macrophage in lung was observed along with markedly increased cytokines expression compared with healthy controls and mild patients. By contrast, neutrophil and macrophage returned to normal level whilst more T and NK cells accumulation were observed in mild patients. Moreover, SARS-CoV-2 infection altered the community interplays of lung epithelial and immune cells interactions between the club and immune cells were higher in COVID-19 patients compared to healthy donors; on the other hand, immune-immune cells interactions appeared the strongest in mild patients.

INTERPRETATION:

SARS-CoV-2 could infect lung epithelium, alter communication patterns between lung epithelial cells and immune system, and drive dysregulated host immune response in COVID-19 patients.

FUNDING:

This project was supported by National Key R&D Program of China (No. 2018YFC1315000/2018YFC1315004), Science and Technology Program Grant Shenzhen (JCYJ20170413161534162), HMRF Hong Kong (17160862), RGC-CRF Hong Kong (C4039-19G), RGC-GRF Hong Kong (14163817), Vice-Chancellor's Discretionary Fund CUHK and CUHK direct grant, Shenzhen Virtual University Park Support Scheme to CUHK Shenzhen Research Institute.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Signal Transduction / Epithelial Cells / SARS-CoV-2 / COVID-19 / Inflammation / Lung Type of study: Observational study Topics: Variants Limits: Humans Language: English Journal: EBioMedicine Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Signal Transduction / Epithelial Cells / SARS-CoV-2 / COVID-19 / Inflammation / Lung Type of study: Observational study Topics: Variants Limits: Humans Language: English Journal: EBioMedicine Year: 2021 Document Type: Article