Pre-existing Cross-reactive Anti-SARS-CoV-2 Cellular Immunity in Hemodialysis and Kidney Transplanted Patients - Implications for COVID-19 Disease Prognosis

确定预测SARS-CoV-2感染后临床结果的免疫学参数至关重要，特别是对高危患者而言。到目前为止，免疫保护的相关因素还没有完全确定，包括T细胞在抗病毒防御中的确切作用。最近的报告表明，在高达60%以前未接触过CoV-2的健康个体中可检测到CoV-2特异性T细胞，这可归因于与低致病性人类“普通感冒”冠状病毒的交叉反应。尽管据推测，这种预先存在的交叉反应性细胞记忆可能会影响COVID-19的严重程度，但目前还没有支持这一假设的数据。血液透析患者和肾移植受者表现出较高的总体感染风险，几项研究强调了感染CoV-2后死亡率的显著增加。然而，这些个体中潜在保护性、交叉反应性T细胞的数量和质量尚未得到检测。因此，我们的研究旨在与健康个体相比，表征先前未暴露于CoV-2的血液透析和肾移植患者中交叉反应性T细胞的患病率、抗原特异性和效应功能。我们将进一步研究免疫抑制药物如何改变这种细胞记忆，以及它在多大程度上与COVID-19的临床严重程度相关。总之，我们将提供关于交叉反应性CoV-2特异性T细胞如何被易感危险因素改变的开创性数据，这可能对COVID-19疾病预后有影响。

Identification of immunological parameters predicting clinical outcomes after SARS-CoV-2 infection is of fundamental importance particularly for patients at risk. So far, immunological correlates of protection are incompletely defined, including the precise role of T cells for anti-viral defence. Recent reports demonstrated that CoV-2 specific T cells are detectable in up to 60% of previously unexposed healthy individuals, being attributable to cross-reactivity with low-pathogenic human “common cold” coronaviruses. Although it is speculated that such pre-existing cross-reactive cellular memory might impact the severity of COVID-19, data supporting this hypothesis is not yet available. Hemodialysis patients and kidney transplant recipients exhibit an elevated overall infection risk with several studies highlighting a significantly increased mortality after infection with CoV-2. However, quantity and quality of potentially protective, cross-reactive T cells has not been examined in these individuals. Our study therefore aims at characterizing the prevalence, antigen-specificities and effector functions of cross-reactive T cells in previously CoV-2 unexposed hemodialysis and kidney transplant patients as compared to healthy individuals. We will further address how such cellular memory is modified by immunosuppressive medication and to what extend it may correlate with clinical severity of COVID-19. In summary, we will provide pioneering data on how cross-reactive CoV-2 specific T cells might be altered by predisposing risk factors, with possible implications for COVID-19 disease prognosis.