학술논문
Lung Spatial Profiling Reveals a T Cell Signature in COPD Patients with Fatal SARS-CoV-2 Infection
Document Type
article
Author
Chen Xi Yang; Michael Tomchaney; Manuel F. Landecho; Borja R. Zamacona; Marta Marin Oto; Javier Zulueta; Joshua Malo; Steve Knoper; Marco Contoli; Alberto Papi; Dragoş M. Vasilescu; Maor Sauler; Christof Straub; Cheryl Tan; Fernando D. Martinez; Deepta Bhattacharya; Ivan O. Rosas; Farrah Kheradmand; Tillie-Louise Hackett; Francesca Polverino
Source
Cells, Vol 11, Iss 1864, p 1864 (2022)
Subject
Language
English
ISSN
2073-4409
Abstract
People with pre-existing lung diseases such as chronic obstructive pulmonary disease (COPD) are more likely to get very sick from SARS-CoV-2 disease 2019 (COVID-19). Still, an interrogation of the immune response to COVID-19 infection, spatially throughout the lung structure, is lacking in patients with COPD. For this study, we characterized the immune microenvironment of the lung parenchyma, airways, and vessels of never- and ever-smokers with or without COPD, all of whom died of COVID-19, using spatial transcriptomic and proteomic profiling. The parenchyma, airways, and vessels of COPD patients, compared to control lungs had (1) significant enrichment for lung-resident CD45RO+ memory CD4+ T cells; (2) downregulation of genes associated with T cell antigen priming and memory T cell differentiation; and (3) higher expression of proteins associated with SARS-CoV-2 entry and primary receptor ubiquitously across the ROIs and in particular the lung parenchyma, despite similar SARS-CoV-2 structural gene expression levels. In conclusion, the lung parenchyma, airways, and vessels of COPD patients have increased T-lymphocytes with a blunted memory CD4 T cell response and a more invasive SARS-CoV-2 infection pattern and may underlie the higher death toll observed with COVID-19.