Lung Spatial Profiling Reveals a T Cell Signature in COPD Patients with Fatal SARS-CoV-2 Infection

Yang, Chen Xi ; Tomchaney, Michael ; Landecho, Manuel F. ; Zamacona, Borja R. ; Marin Oto, Marta (Universidad de Zaragoza) ; Zulueta, Javier ; Malo, Joshua ; Knoper, Steve ; Contoli, Marco ; Papi, Alberto ; Vasilescu, Dragos M. ; Sauler, Maor ; Straub, Christof ; Tan, Cheryl ; Martinez, Fernando D. ; Bhattacharya, Deepta ; Rosas, Ivan O. ; Kheradmand, Farrah ; Hackett, Tillie-Louise ; Polverino, Francesca

Resumen: 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.

Idioma: Inglés

DOI: 10.3390/cells11121864

Año: 2022

Publicado en: Cells 11, 12 (2022), 1864 [15 pp.]
ISSN: 2073-4409

Factor impacto JCR: 6.0 (2022)

Categ. JCR: CELL BIOLOGY rank: 60 / 191 = 0.314 (2022) - Q2 - T1

Factor impacto CITESCORE: 9.0 - Medicine (Q1)

Factor impacto SCIMAGO: 1.537 - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1)

Tipo y forma: Article (Published version)

Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)