A molecular single-cell lung atlas of lethal COVID-19.
Nature
; 595(7865): 114-119, 2021 07.
Article
in English
| MEDLINE | ID: covidwho-1207147
ABSTRACT
Respiratory failure is the leading cause of death in patients with severe SARS-CoV-2 infection1,2, but the host response at the lung tissue level is poorly understood. Here we performed single-nucleus RNA sequencing of about 116,000 nuclei from the lungs of nineteen individuals who died of COVID-19 and underwent rapid autopsy and seven control individuals. Integrated analyses identified substantial alterations in cellular composition, transcriptional cell states, and cell-to-cell interactions, thereby providing insight into the biology of lethal COVID-19. The lungs from individuals with COVID-19 were highly inflamed, with dense infiltration of aberrantly activated monocyte-derived macrophages and alveolar macrophages, but had impaired T cell responses. Monocyte/macrophage-derived interleukin-1ß and epithelial cell-derived interleukin-6 were unique features of SARS-CoV-2 infection compared to other viral and bacterial causes of pneumonia. Alveolar type 2 cells adopted an inflammation-associated transient progenitor cell state and failed to undergo full transition into alveolar type 1 cells, resulting in impaired lung regeneration. Furthermore, we identified expansion of recently described CTHRC1+ pathological fibroblasts3 contributing to rapidly ensuing pulmonary fibrosis in COVID-19. Inference of protein activity and ligand-receptor interactions identified putative drug targets to disrupt deleterious circuits. This atlas enables the dissection of lethal COVID-19, may inform our understanding of long-term complications of COVID-19 survivors, and provides an important resource for therapeutic development.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Single-Cell Analysis
/
SARS-CoV-2
/
COVID-19
/
Lung
Type of study:
Observational study
/
Prognostic study
Topics:
Long Covid
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
English
Journal:
Nature
Year:
2021
Document Type:
Article
Affiliation country:
S41586-021-03569-1
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