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

Abstract

Supplemental Digital Content is available in the text. Background. 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.