A molecular single-cell lung atlas of lethal COVID-19 Journal Article


Authors: Melms, J. C.; Biermann, J.; Huang, H.; Wang, Y.; Nair, A.; Tagore, S.; Katsyv, I.; Rendeiro, A. F.; Amin, A. D.; Schapiro, D.; Frangieh, C. J.; Luoma, A. M.; Filliol, A.; Fang, Y.; Ravichandran, H.; Clausi, M. G.; Alba, G. A.; Rogava, M.; Chen, S. W.; Ho, P.; Montoro, D. T.; Kornberg, A. E.; Han, A. S.; Bakhoum, M. F.; Anandasabapathy, N.; Suárez-Fariñas, M.; Bakhoum, S. F.; Bram, Y.; Borczuk, A.; Guo, X. V.; Lefkowitch, J. H.; Marboe, C.; Lagana, S. M.; Del Portillo, A.; Zorn, E.; Markowitz, G. S.; Schwabe, R. F.; Schwartz, R. E.; Elemento, O.; Saqi, A.; Hibshoosh, H.; Que, J.; Izar, B.
Article Title: A molecular single-cell lung atlas of lethal COVID-19
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-1β 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. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
Keywords: bacteria (microorganisms); sars coronavirus
Journal Title: Nature
Volume: 595
Issue: 7865
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2021-07-01
Start Page: 114
End Page: 119
Language: English
DOI: 10.1038/s41586-021-03569-1
PUBMED: 33915568
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 2 August 2021 -- Source: Scopus
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  1. Samuel F Bakhoum
    37 Bakhoum