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 ten Tx in comparison to 26 nonimmunosuppressed (non-Tx) COVID-19 patients. RESULTS: Tx-patients (seven renal, one lung, and two combined pancreas-kidney transplants) 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 days 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 pro-inflammatory 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 has implications for the handling of SARS-CoV-2-infected Tx patients and raises hopes for effective vaccination in this cohort.Supplemental Visual Abstract; http://links.lww.com/TP/C186.
BACKGROUND: The ability of transplant (Tx)-patients to generate a protective antiviral response under immunosuppression is pivotal in COVID-19infection. However, analysis of immunity against SARS-COV-2 is currently lacking. METHODS: Here, we analyzed T cell immunity directed against SARS-CoV-2spike-, membrane-, and nucleocapsid-protein by flow cytometry and spike-specific neutralizing antibodies in ten Tx in comparison to 26 nonimmunosuppressed (non-Tx) COVID-19patients. RESULTS: Tx-patients (seven renal, one lung, and two combined pancreas-kidney transplants) 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 days 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 pro-inflammatory 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 has implications for the handling of SARS-CoV-2-infected Tx patients and raises hopes for effective vaccination in this cohort.Supplemental Visual Abstract; http://links.lww.com/TP/C186.
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Authors: Jan-Stephan F Sanders; Frederike J Bemelman; A Lianne Messchendorp; Carla C Baan; Debbie van Baarle; Rob van Binnendijk; Dimitri A Diavatopoulos; Sophie C Frölke; Daryl Geers; Corine H GeurtsvanKessel; Gerco den Hartog; Marieke van der Heiden; Celine Imhof; Marcia M L Kho; Marion P G Koopmans; S Reshwan K Malahe; Wouter B Mattheussens; Renate van der Molen; Djenolan van Mourik; Ester B M Remmerswaal; Nynke Rots; Priya Vart; Rory D de Vries; Ron T Gansevoort; Luuk B Hilbrands; Marlies E J Reinders Journal: Transplantation Date: 2022-04-01 Impact factor: 4.939
Authors: Korbinian Wünsch; Olympia E Anastasiou; Mira Alt; Leonie Brochhagen; Maxim Cherneha; Laura Thümmler; Lukas van Baal; Rabea J Madel; Monika Lindemann; Christian Taube; Oliver Witzke; Hana Rohn; Adalbert Krawczyk; Sarah Jansen Journal: Viruses Date: 2022-04-01 Impact factor: 5.048
Authors: Mario Fernández-Ruiz; Beatriz Olea; Patricia Almendro-Vázquez; Estela Giménez; Alberto Marcacuzco; Rafael San Juan; Iago Justo; Jorge Calvo-Pulido; Álvaro García-Sesma; Alejandro Manrique; Oscar Caso; Félix Cambra; Paloma Talayero; Francisco López-Medrano; María José Remigia; Tamara Ruiz-Merlo; Patricia Parra; Estela Paz-Artal; Carlos Jiménez; Carmelo Loinaz; David Navarro; Rocío Laguna-Goya; José M Aguado Journal: Am J Transplant Date: 2021-06-25 Impact factor: 9.369