COVID-19 and cancer are major health threats, and individuals may develop both simultaneously. Recent studies have indicated that cancer patients 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 pathological 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 pathological fibroblasts. These pre-existing conditions in lung cancer patients 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 lung cancer patients 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 lung cancer patients.

中文翻译：

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单细胞转录组学揭示肺癌患者中预先存在的 COVID-19 易感因素

COVID-19 和癌症是主要的健康威胁，个人可能会同时患上这两种疾病。最近的研究表明，癌症患者特别容易感染 COVID-19，但人们对这种关联背后的分子机制仍知之甚少。为了弥补这一知识差距，我们收集了来自 COVID-19、肺腺癌、小细胞肺癌患者和正常肺的单细胞 RNA 测序数据，以进行综合分析。我们表征了疾病中细胞群、基因表达和细胞间通讯失调的改变。我们的分析确定了 COVID-19 和肺癌共有的病理状况，包括上皮细胞中 TMPRSS2 表达上调、巨噬细胞介导的炎症反应更强、T 细胞反应抑制增加以及病理性成纤维细胞导致纤维化风险升高。肺癌患者的这些预先存在的病症可能会导致更严重的炎症、纤维化和感染 COVID-19 后的适应性免疫反应减弱。我们的研究结果揭示了导致肺癌患者 COVID-19 风险增加的潜在分子机制，并提出了该人群中 COVID-19 的预防和治疗目标。意义：我们的工作揭示了导致肺癌患者容易感染 COVID-19 的潜在分子机制。