Background: Adaptive immune responses to structural proteins of the virion play a crucial role in protection against coronavirus disease 2019 (COVID-19). We therefore studied T cell responses against multiple SARS-CoV-2 structural proteins in a large cohort using a simple, fast, and high-throughput approach. Methods: An automated interferon gamma release assay (IGRA) for the Nucleocapsid (NC)-, Membrane (M)-, Spike-C-terminus (SCT)-, and N-terminus-protein (SNT)-specific T cell responses was performed using fresh whole blood from study subjects with convalescent, confirmed COVID-19 (n = 177, more than 200 days post infection), exposed household members (n = 145), and unexposed controls (n = 85). SARS-CoV-2-specific antibodies were assessed using Elecsys® Anti-SARS-CoV-2 (Ro-N-Ig) and Anti-SARS-CoV-2-ELISA (IgG) (EI-S1-IgG). Results: 156 of 177 (88%) previously PCR confirmed cases were still positive by Ro-N-Ig more than 200 days after infection. In T cells, most frequently the M-protein was targeted by 88% seropositive, PCR confirmed cases, followed by SCT (85%), NC (82%), and SNT (73%), whereas each of these antigens was recognized by less than 14% of non-exposed control subjects. Broad targeting of these structural virion proteins was characteristic of convalescent SARS-CoV-2 infection; 68% of all seropositive individuals targeted all four tested antigens. Indeed, anti-NC antibody titer correlated loosely, but significantly with the magnitude and breadth of the SARS-CoV-2-specific T cell response. Age, sex, and body mass index were comparable between the different groups. Conclusion: SARS-CoV-2 seropositivity correlates with broad T cell reactivity of the structural virus proteins at 200 days after infection and beyond. The SARS-CoV-2-IGRA can facilitate large scale determination of SARS-CoV-2-specific T cell responses with high accuracy against multiple targets.
FörderungenEuropean Union's Horizon 2020 research and innovation programme, ORCHESTRA Marie-Sklodowska-Curie Program Training Network for the Immunotherapy of Cancer and for Optimizing adoptive T cell therapy of cancer - H2020 Program of the European Union German Ministry for Education and Research University of Bielefeld University of Bonn Helmholtz Centre Munich LMU Munich University Hospital Bavarian State Ministry of Science and the Arts Bavarian Ministry for Science and Arts Hector foundation International Doctoral Program i Target Jose-Carreras Foundation Bavarian Ministry of Economic affairs (m4 award) Fritz-Bender-Foundation German Research Foundation (DFG) European Research Council, ARMOR-T Bundesministerium fur Bildung und Forschung Project Oncoattract and CONTRACT LMU Munich's Institutional Strategy LMUexcellent within the German Excellence Initiative Ernst-Jung-Stiftung German Cancer Aid Elite Network of Bavaria Program for Advancement of Corona Research