COVID-19 is caused by the coronavirus SARS-CoV-2 and currently has detrimental human health, community and economic impacts around the world. It is unclear why some SARS-CoV-2-positive individuals remain asymptomatic, while others develop severe symptoms. Baseline pulmonary levels of anti-viral leukocytes, already residing in the lung prior to infection, may orchestrate an effective early immune response and prevent severe symptoms. Using "in silico flow cytometry", we deconvoluted the levels of all seven types of anti-viral leukocytes in 1,927 human lung tissues. Baseline levels of CD8+ T cells, resting NK cells and activated NK cells, as well as cytokines that recruit these, are significantly lower in lung tissues with high expression of the SARS-CoV-2 entry receptor ACE2. We observe this in univariate analyses, in multivariate analyses, and in two independent datasets. Relevantly, ACE2 mRNA and protein levels very strongly correlate in human cells and tissues. Above findings also largely apply to the SARS-CoV-2 entry protease TMPRSS2. Both SARS-CoV-2-infected lung cells and COVID-19 lung tissues show upregulation of CD8+ T cell- and NK cell-recruiting cytokines. Moreover, tissue-resident CD8+ T cells and inflammatory NK cells are significantly more abundant in bronchoalveolar lavages from mildly affected COVID-19 patients, compared to severe cases. This suggests that these lymphocytes are important for preventing severe symptoms. Elevated ACE2 expression increases sensitivity to coronavirus infection. Thus, our results suggest that some individuals may be exceedingly susceptible to develop severe COVID-19 due to concomitant high pre-existing ACE2 and TMPRSS expression and low baseline cytotoxic lymphocyte levels in the lung.

中文翻译：

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CD8+ T 细胞和 NK 细胞的基线肺水平与 SARS-CoV-2 进入受体 ACE2 的表达呈负相关。

COVID-19 由冠状病毒 SARS-CoV-2 引起，目前对世界各地的人类健康、社区和经济造成不利影响。目前尚不清楚为什么一些 SARS-CoV-2 阳性个体仍然无症状，而另一些则出现严重症状。在感染前已经存在于肺部的抗病毒白细胞的基线肺水平可以协调有效的早期免疫反应并预防严重症状。使用“计算机流式细胞仪”，我们对 1,927 个人类肺组织中所有七种抗病毒白细胞的水平进行了反卷积。在 SARS-CoV-2 进入受体 ACE2 高表达的肺组织中，CD8+ T 细胞、静息 NK 细胞和活化 NK 细胞以及募集这些细胞的细胞因子的基线水平显着降低。我们在单变量分析中观察到这一点，在多变量分析和两个独立的数据集中。相关地，ACE2 mRNA 和蛋白质水平在人类细胞和组织中具有很强的相关性。上述发现在很大程度上也适用于 SARS-CoV-2 进入蛋白酶 TMPRSS2。SARS-CoV-2 感染的肺细胞和 COVID-19 肺组织均显示 CD8+ T 细胞和 NK 细胞募集细胞因子的上调。此外，与严重病例相比，轻度感染 COVID-19 患者的支气管肺泡灌洗液中组织驻留的 CD8+ T 细胞和炎性 NK 细胞明显更丰富。这表明这些淋巴细胞对于预防严重症状很重要。ACE2 表达升高会增加对冠状病毒感染的敏感性。因此，