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About: The optimal management in transplant recipients with COVID‐19 remains uncertain. The main concern is the ability of immunosuppressed patients to generate sufficient immunity for antiviral protection. Here, we report on immune monitoring facilitating a successful outcome of severe SARS‐CoV‐2‐associated pneumonia, meningoencephalitis, gastroenteritis and acute kidney and pancreas graft failure in a pancreas‐kidney transplant recipient. Despite the very low numbers of circulating B‐, NK‐, and T‐cells identified in follow up, a strong SARS‐CoV‐2 reactive T‐cell response was observed. Importantly, we detected T‐cells reactive to Spike, Membrane, and Nucleocapsid proteins of SARS‐CoV‐2 with majority of T‐cells showing polyfunctional pro‐inflammatory Th1 phenotype at all analyzed time points. Antibodies against Spike protein were also detected with increasing titers in follow up. Neutralization tests confirmed their antiviral protection. A correlation between cellular and humoral immunity was observed underscoring the specificity of demonstrated data. We conclude that analyzing the kinetics of non‐specific and SARS‐CoV‐2‐reactive cellular and humoral immunity can facilitate the clinical decision on immunosuppression adjustment and allow successful outcome as demonstrated in the current clinical case. While the antiviral protection of the detected SARS‐CoV‐2‐reactive T‐cells requires further evaluation, our data prove an ability mounting a strong SARS‐CoV‐2‐reactive T‐cell response with functional capacity in immunosuppressed patients.

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