Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces a T cell response that most likely contributes to virus control in COVID-19 patients but may also induce immunopathology. Until now, the cytotoxic T cell response has not been very well characterized in COVID-19 patients. Here, we analyzed the differentiation and cytotoxic profile of T cells in 30 cases of mild COVID-19 during acute infection. SARS-CoV-2 infection induced a cytotoxic response of CD8⁺ T cells, but not CD4⁺ T cells, characterized by the simultaneous production of granzyme A and B as well as perforin within different effector CD8⁺ T cell subsets. PD-1-expressing CD8⁺ T cells also produced cytotoxic molecules during acute infection, indicating that they were not functionally exhausted. However, in COVID-19 patients over the age of 80 years, the cytotoxic T cell potential was diminished, especially in effector memory and terminally differentiated effector CD8⁺ cells, showing that elderly patients have impaired cellular immunity against SARS-CoV-2. Our data provide valuable information about T cell responses in COVID-19 patients that may also have important implications for vaccine development.

中文翻译：

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老年 COVID-19 患者的细胞毒性 CD8+ T 细胞反应受损。

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染会诱导 T 细胞反应，这很可能有助于 COVID-19 患者的病毒控制，但也可能引发免疫病理学。到目前为止，COVID-19 患者的细胞毒性 T 细胞反应尚未得到很好的表征。在这里，我们分析了 30 例轻度 COVID-19 急性感染期间 T 细胞的分化和细胞毒性特征。^{SARS-CoV-2 感染诱导 CD8 +} T 细胞而非 CD4 ⁺ T 细胞的细胞毒性反应，其特征是在不同效应 CD8 ⁺ T 细胞亚群内同时产生颗粒酶 A 和 B 以及穿孔素。表达 PD-1 的 CD8 ⁺ T 细胞在急性感染期间也会产生细胞毒性分子，表明它们的功能并未耗尽。然而，在80岁以上的COVID-19患者中，细胞毒性T细胞潜力减弱，尤其是效应记忆和终末分化效应CD8 ⁺细胞，表明老年患者针对SARS-CoV-2的细胞免疫受损。我们的数据提供了有关 COVID-19 患者 T 细胞反应的宝贵信息，这也可能对疫苗开发产生重要影响。