Abstract
Background: Waning of immunoglobulin G (IgG) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complicates the diagnosis of past infection. The durability of T-cell memory against SARS-CoV-2 remains unclear, and most current T-cell protocols are unsuited for large-scale automation.
Methods: Whole-blood samples from 31 patients with verified past coronavirus disease 2019 (COVID-19) and 46 controls, of whom 40 received COVID-19 vaccine, were stimulated with peptides spanning the nucleocapsid (NC) or spike 1 (S1) regions of SARS-CoV-2 and analyzed for interferon γ in supernatant plasma. Diagnostic accuracy of these assays was evaluated against serum anti-NC and anti-receptor-binding domain S1-IgG.
Results: Induction of interferon γ in whole blood by NC or S1 peptides diagnosed past COVID-19 with high accuracy (area under the receiver operating characteristic curve, 0.93 and 0.95, respectively). In accordance with previous studies, NC-IgG levels rapidly waned with only 5 of 17 patients (29%) remaining seropositive >180 days after infection. By contrast, NC peptide-induced T-cell memory responses remained in 13 of 17 study participants (76%) >180 days after infection (P = .01 for comparison with NC-IgG; McNemar test). After 2 vaccine doses, all 18 donors exhibited S1-specific T-cell memory.
Conclusions: Cytokine release assays for the monitoring of T-cell memory in whole blood may be useful for evaluating complications following unverified past COVID-19 and for long-term assessment of vaccine-induced T-cell immunity.
Clinical trials registration: EudraCT 2021-000349-42.
Keywords: COVID-19; Cytokine release assay; SARS-CoV-2; T cells; nucleocapsid; spike.
【저자키워드】 COVID-19, SARS-CoV-2, T cells, nucleocapsid, Spike., Cytokine release assay, 【초록키워드】 coronavirus disease, IgG, Coronavirus disease 2019, coronavirus, COVID-19 vaccine, vaccine doses, protocol, Trial, antibody, T cells, Infection, interferon, peptide, Diagnosis, cytokine, severe acute respiratory syndrome Coronavirus, memory, serum, Immunoglobulin G, Diagnostic accuracy, Region, Immunoglobulin, Whole blood, nucleocapsid, clinical, Patient, peptides, Complication, plasma, T-cell, respiratory, characteristic, seropositive, Donor, T-cell immunity, memory response, receiver operating characteristic, interferon γ, acute respiratory syndrome, induction, acute respiratory syndrome coronavirus, Previous studies, acute respiratory syndrome coronavirus 2, Blood samples, IgG levels, EudraCT, anti-receptor-binding domain, receiver, high accuracy, supernatant, controls, stimulated, analyzed, remained, diagnosed, evaluated, exhibited, study participant, complicate, waned, 【제목키워드】 Release, Rapid,