Yang, C. X.; Tomchaney, M.; Landecho Acha, Manuel Fortún
; Recalde Zamacona, Borja
; Marin Oto, Marta
; Zulueta, J.; Malo, J.; Knoper, S.; Contoli, M.; Papi, A.; Vasilescu, D. M.; Sauler, M.; Straub, C.; Tan, C.; Martínez, F. D.; Bhattacharya, D.; Rosas, I. O.; Kheradmand, F.; Hackett, T. L.; Polverino, F. (Autor de correspondencia)
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.