Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic 1 , 2 . Clinical manifestations of COVID-19 vary, ranging from asymptomatic infection to respiratory failure. The mechanisms that determine such variable outcomes remain unresolved. Here we investigated CD4 + T cells that are reactive against the spike glycoprotein of SARS-CoV-2 in the peripheral blood of patients with COVID-19 and SARS-CoV-2-unexposed healthy donors. We detected spike-reactive CD4 + T cells not only in 83% of patients with COVID-19 but also in 35% of healthy donors. Spike-reactive CD4 + T cells in healthy donors were primarily active against C-terminal epitopes in the spike protein, which show a higher homology to spike glycoproteins of human endemic coronaviruses, compared with N-terminal epitopes. Spike-protein-reactive T cell lines generated from SARS-CoV-2-naive healthy donors responded similarly to the C-terminal region of the spike proteins of the human endemic coronaviruses 229E and OC43, as well as that of SARS-CoV-2. This results indicate that spike-protein cross-reactive T cells are present, which were probably generated during previous encounters with endemic coronaviruses. The effect of pre-existing SARS-CoV-2 cross-reactive T cells on clinical outcomes remains to be determined in larger cohorts. However, the presence of spike-protein cross-reactive T cells in a considerable fraction of the general population may affect the dynamics of the current pandemic, and has important implications for the design and analysis of upcoming trials investigating COVID-19 vaccines. A study of patients with COVID-19 and healthy donors found CD4 + T cells that react to the spike protein of SARS-CoV-2 and human endemic coronaviruses; however, the effect of pre-existing SARS-CoV-2 cross-reactive T cells on clinical outcomes remains to be determined.

中文翻译：

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健康供体和 COVID-19 患者的 SARS-CoV-2 反应性 T 细胞

严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 已导致迅速蔓延的 2019 年冠状病毒病 (COVID-19) 大流行 1 , 2 。COVID-19 的临床表现多种多样，从无症状感染到呼吸衰竭不等。决定这种可变结果的机制仍未解决。在这里，我们研究了对 COVID-19 患者和未暴露于 SARS-CoV-2 的健康供体的外周血中的 SARS-CoV-2 刺突糖蛋白有反应的 CD4 + T 细胞。我们不仅在 83% 的 COVID-19 患者中，而且在 35% 的健康供体中检测到了尖峰反应性 CD4 + T 细胞。健康供体中的刺突反应性 CD4 + T 细胞主要针对刺突蛋白中的 C 端表位具有活性，这与人类地方性冠状病毒的刺突糖蛋白具有更高的同源性，与 N 端表位相比。由 SARS-CoV-2 未感染健康供体产生的刺突蛋白反应性 T 细胞系对人类地方性冠状病毒 229E 和 OC43 以及 SARS-CoV-2 刺突蛋白的 C 末端区域的反应相似. 这一结果表明存在刺突蛋白交叉反应性 T 细胞，这可能是在以前与地方性冠状病毒相遇时产生的。预先存在的 SARS-CoV-2 交叉反应性 T 细胞对临床结果的影响仍有待在更大的队列中确定。然而，相当一部分普通人群中刺突蛋白交叉反应性 T 细胞的存在可能会影响当前大流行的动态，并对即将进行的 COVID-19 疫苗试验的设计和分析具有重要意义。一项针对 COVID-19 患者和健康供体的研究发现 CD4 + T 细胞对 SARS-CoV-2 和人类地方性冠状病毒的刺突蛋白有反应；然而，预先存在的 SARS-CoV-2 交叉反应性 T 细胞对临床结果的影响仍有待确定。