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.
Keywords: COVID-19; T cells; chronic obstructive pulmonary disease (COPD).
【저자키워드】 COVID-19, T cells, chronic obstructive pulmonary disease (COPD)., 【초록키워드】 SARS-CoV-2, immune response, Gene Expression, T cells, SARS-COV-2 infection, lung, Lung disease, CD4, COPD, memory, Antigen, Protein, T cell, T-lymphocytes, COVID-19 infection, Lung diseases, Patient, death, receptor, expression, patients, CD45RO, T cell response, memory T cell, proteomic, pulmonary disease, Smokers, chronic obstructive pulmonary disease, lung parenchyma, airways, chronic obstructive pulmonary disease (COPD), obstructive pulmonary disease, structural gene, T-lymphocyte, SARS-CoV-2 disease, SARS-CoV-2 entry, vessels, priming, downregulation, significant enrichment, CD45, immune microenvironment, ROIs, memory T, parenchyma, transcriptomic, vessel, Cell, invasive, SARS-CoV-2 disease 2019, died, characterized, sick, underlie, chronic obstructive, ROI, Still, with COVID-19, 【제목키워드】 SARS-CoV-2, Profiling, signature,