The SARS-CoV-2 pandemic has so far claimed over three and a half million lives worldwide. Though the SARS-CoV-2 mediated disease COVID-19 has first been characterized by an infection of the upper airways and the lung, recent evidence suggests a complex disease including gastrointestinal symptoms. Even if a direct viral tropism of intestinal cells has recently been demonstrated, it remains unclear, whether gastrointestinal symptoms are caused by direct infection of the gastrointestinal tract by SARS-CoV-2 or whether they are a consequence of a systemic immune activation and subsequent modulation of the mucosal immune system. To better understand the cause of intestinal symptoms we analyzed biopsies of the small intestine from SARS-CoV-2 infected individuals. Applying qRT-PCR and immunohistochemistry, we detected SARS-CoV-2 RNA and nucleocapsid protein in duodenal mucosa. In addition, applying imaging mass cytometry and immunohistochemistry, we identified histomorphological changes of the epithelium, which were characterized by an accumulation of activated intraepithelial CD8⁺ T cells as well as epithelial apoptosis and subsequent regenerative proliferation in the small intestine of COVID-19 patients. In summary, our findings indicate that intraepithelial CD8⁺ T cells are activated upon infection of intestinal epithelial cells with SARS-CoV-2, providing one possible explanation for gastrointestinal symptoms associated with COVID-19.

迄今为止，SARS-CoV-2 大流行已夺去全球超过 350 万人的生命。尽管 SARS-CoV-2 介导的疾病 COVID-19 最初的特征是上呼吸道和肺部感染，但最近的证据表明这是一种包括胃肠道症状在内的复杂疾病。即使最近证明了肠道细胞的直接病毒趋向性，仍不清楚胃肠道症状是由 SARS-CoV-2 直接感染胃肠道引起的，还是系统免疫激活和随后调节的结果的粘膜免疫系统。为了更好地了解肠道症状的原因，我们分析了 SARS-CoV-2 感染者的小肠活检。应用 qRT-PCR 和免疫组织化学，我们在十二指肠粘膜中检测到 SARS-CoV-2 RNA 和核衣壳蛋白。此外，应用成像质量流式细胞术和免疫组织化学，我们确定了上皮细胞的组织形态学变化，其特征是活化的上皮内 CD8 的积累⁺ T 细胞以及 COVID-19 患者小肠中的上皮细胞凋亡和随后的再生性增殖。总之，我们的研究结果表明，肠上皮细胞感染 SARS-CoV-2 后，上皮内 CD8 ^{+ T 细胞被激活，这为与 COVID-19 相关的胃肠道症状提供了一种可能的解释。}