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.
【저자키워드】 COVID-19, SARS-CoV-2, T cell response, interferon gamma release assay (IGRA), high through put, 【초록키워드】 coronavirus disease, IgG, Coronavirus disease 2019, immune response, T cells, SARS-COV-2 infection, Infection, Sex, virus, Antigen, Protein, T cell, body mass index, PCR, Whole blood, nucleocapsid, immune responses, T cell responses, Antibody titer, Control, Seropositivity, membrane, structural proteins, antigens, automated, large cohort, targets, structural protein, convalescent, characteristic, SARS-CoV-2-specific antibodies, seropositive, specific antibodies, breadth, interferon gamma, followed by, body mass, fresh whole blood, confirmed case, SARS-CoV-2-specific antibody, control subjects, subject, confirmed cases, virion, high accuracy, positive, C-terminus, Elecsys, approach, Result, tested, significantly, was performed, facilitate, less, correlated, magnitude, comparable, reactivity, groups, days post infection, Elecsy, SCT, seropositive individual, were assessed, 【제목키워드】 Release, T cell, Gamma, structural proteins, assessment, throughput, targeting,