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

• Applicant: Professorin Katja Kotsch, Ph.D.
• Subject Area: Nephrology ; Immunology
• Term: from 2021 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 458681590

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.

• DFG Programme: Research Grants