Coronavirus disease 2019 (COVID-19) displays high clinical variability but the parameters that determine disease severity are still unclear. Pre-existing T cell memory has been hypothesized as a protective mechanism but conclusive evidence is lacking. Here we demonstrate that all unexposed individuals harbor SARS-CoV-2-specific memory T cells with marginal cross-reactivity to common cold corona and other unrelated viruses. They display low functional avidity and broad protein target specificities and their frequencies correlate with the overall size of the CD4+ memory compartment reflecting the immunological age of an individual. COVID-19 patients have strongly increased SARS-CoV-2-specific inflammatory T cell responses that are correlated with severity. Strikingly however, patients with severe COVID-19 displayed lower TCR functional avidity and less clonal expansion. Our data suggest that a low avidity pre-existing T cell memory negatively impacts on the T cell response quality against neoantigens such as SARS-CoV-2, which may predispose to develop inappropriate immune reactions especially in the elderly. We propose the immunological age as an independent risk factor to develop severe COVID-19.

中文翻译：

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先前存在的T细胞记忆是老年人严重1 COVID-19的危险因素

冠状病毒病2019（COVID-19）显示出很高的临床变异性，但确定疾病严重程度的参数仍不清楚。已有的T细胞记忆被认为是一种保护机制，但缺乏确凿的证据。在这里，我们证明所有未暴露的个体都带有SARS-CoV-2特异性记忆T细胞，与普通感冒日冕和其他无关病毒的边缘交叉反应。它们显示出低功能亲和力和广泛的蛋白质靶特异性，并且它们的频率与反映个体免疫年龄的CD4 +记忆区室的整体大小相关。COVID-19患者的SARS-CoV-2特异性炎性T细胞反应强烈增加，与严重程度相关。然而，惊人的是 严重COVID-19的患者表现出较低的TCR功能亲和力和较少的克隆扩增。我们的数据表明，先前存在的低亲和力的T细胞记忆会对T细胞针对新抗原（例如SARS-CoV-2）的反应质量产生负面影响，这可能导致特别是在老年人中发展出不适当的免疫反应。我们建议免疫年龄是发展严重COVID-19的独立危险因素。