Publicaciones científicas
Lung Spatial Profiling Reveals a T Cell Signature in COPD Patients with Fatal SARS-CoV-2 Infectio
Chen Xi Yang 1 2 , Michael Tomchaney 3 , Manuel F Landecho 4 , Borja R Zamacona 4 , Marta Marin Oto 4 , Javier Zulueta 5 , Joshua Malo 6 , Steve Knoper 6 , Marco Contoli 7 , Alberto Papi 7 , Dragoş M Vasilescu 1 8 , Maor Sauler 9 , Christof Straub 10 , Cheryl Tan 10 , Fernando D Martinez 3 , Deepta Bhattacharya 11 , Ivan O Rosas 12 , Farrah Kheradmand 12 , Tillie-Louise Hackett 1 2 , Francesca Polverino 12
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.
CITA DEL ARTÍCULO Cells. 2022 Jun 7;11(12):1864. doi: 10.3390/cells11121864
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