Single-Cell Transcriptomics Reveals Pre-existing COVID-19 Vulnerability Factors in Lung Cancer Patients

Abstract Coronavirus disease 2019 (COVID-19) and cancer are major health threats, and individuals may develop both simultaneously. Recent studies have indicated that patients with cancer are particularly vulnerable to COVID-19, but the molecular mechanisms underlying the associations remain poorly understood. To address this knowledge gap, we collected single-cell RNA-sequencing data from COVID-19, lung adenocarcinoma, small cell lung carcinoma patients, and normal lungs to perform an integrated analysis. We characterized altered cell populations, gene expression, and dysregulated intercellular communication in diseases. Our analysis identified pathologic conditions shared by COVID-19 and lung cancer, including upregulated TMPRSS2 expression in epithelial cells, stronger inflammatory responses mediated by macrophages, increased T-cell response suppression, and elevated fibrosis risk by pathologic fibroblasts. These pre-existing conditions in patients with lung cancer may lead to more severe inflammation, fibrosis, and weakened adaptive immune response upon COVID-19 infection. Our findings revealed potential molecular mechanisms driving an increased COVID-19 risk in patients with lung cancer and suggested preventive and therapeutic targets for COVID-19 in this population. Implications: Our work reveals the potential molecular mechanisms contributing to the vulnerability to COVID-19 in patients with lung cancer.