Abstract

RationalePeople with pre-existing lung diseases like chronic obstructive pulmonary disease (COPD) are more likely to get very sick from SARS-CoV-2 disease 2019 (COVID-19), but an interrogation of the immune response to COVID-19 infection, spatial throughout the lung structure is lacking in patients with COPD. ObjectivesTo profile the immune microenvironment of lung parenchyma, airways, and vessels of never- and ever-smokers with or without COPD, whom all died of COVID-19, using spatial transcriptomic and proteomic profiling. FindingsThe parenchyma, airways, and vessels of COPD patients, compared to control lungs had: 1) significant enrichment for lung resident CD45RO+ memory T cells; 2) downregulation of genes associated with T cell antigen-priming and memory T cell differentiation; 3) higher expression of proteins associated with SARS-CoV-2 entry and major receptor ubiquitously across the ROIs and in particular the lung parenchyma, despite similar SARS-CoV-2 structural gene expression levels. ConclusionsThe lung parenchyma, airways, and vessels of COPD patients have increased T-lymphocytes with a blunted memory T cell response and a more invasive SARS-CoV-2 infection pattern, and may underlie the higher death toll observed with COVID-19.