The Magnitude and Functionality of SARS-CoV-2 Reactive Cellular and Humoral Immunity in Transplant Population Is Similar to the General Population Despite Immunosuppression

Thieme, Constantin J.; Anft, Moritz; Paniskaki, Krystallenia; Blazquez-Navarro, Arturo; Doevelaar, Adrian; Seibert, Felix S.; Hoelzer, Bodo; Justine Konik, Margarethe; Meister, Toni L.; Pfaender, Stephanie; Steinmann, Eike; Moritz Berger, Marc; Brenner, Thorsten; Kölsch, Uwe; Dolff, Sebastian; Roch, Toralf; Witzke, Oliver; Schenker, Peter; Viebahn, Richard; Stervbo, Ulrik; Westhoff, Timm H.; Babel, Nina

The ability of transplant (Tx) patients to generate a protective antiviral response under immunosuppression is pivotal in COVID-19 infection. However, analysis of immunity against SARS-CoV-2 is currently lacking. METHODS. Here, we analyzed T cell immunity directed against SARS-CoV-2 spike-, membrane-, and nucleocapsid-protein by flow cytometry and spike-specific neutralizing antibodies in 10 Tx in comparison to 26 nonimmunosuppressed (non-Tx) COVID-19 patients. RESULTS. Tx patients (7 renal, 1 lung, and 2 combined pancreas-kidney Txs) were recruited in this study during the acute phase of COVID-19 with a median time after SARS-CoV-2-positivity of 3 and 4 d for non-Tx and Tx patients, respectively. Despite immunosuppression, we detected antiviral CD4(+) T cell-response in 90% of Tx patients. SARS-CoV-2–reactive CD4(+) T cells produced multiple proinflammatory cytokines, indicating their potential protective capacity. Neutralizing antibody titers did not differ between groups. SARS-CoV-2–reactive CD8(+) T cells targeting membrane- and spike-protein were lower in Tx patients, albeit without statistical significance. However, frequencies of anti-nucleocapsid–protein-reactive, and anti-SARS-CoV-2 polyfunctional CD8(+) T cells, were similar between patient cohorts. Tx patients showed features of a prematurely aged adaptive immune system, but equal frequencies of SARS-CoV-2–reactive memory T cells. CONCLUSIONS. In conclusion, a polyfunctional T cell immunity directed against SARS-CoV-2 proteins as well as neutralizing antibodies can be generated in Tx patients despite immunosuppression. In comparison to nonimmunosuppressed patients, no differences in humoral and cellular antiviral-immunity were found. Our data presenting the ability to generate SARS-CoV-2–specific immunity in immunosuppressed patients have implications for the handling of SARS-CoV-2–infected Tx patients and raise hopes for effective vaccination in this cohort.