Comparison of Two Commercially Available Interferon-γ Release Assays for T-Cell-Mediated Immunity and Evaluation of Humoral Immunity against SARS-CoV-2 in Healthcare Workers.

Cellular immunity against SARS-CoV-2 is an important component of the immune response to the virus. At present, two such tests based on interferon-gamma release (interferon-γ release assays, IGRAs) are available-Quan-T-Cell SARS-CoV-2 by EUROIMMUN and T-SPOT.COVID by Oxford Immunotec. In this paper, we compared the results of these two tests in 90 subjects employed at the Public Health Institute Ostrava who had previously undergone COVID-19 infection or were vaccinated against that disease. To the best of our knowledge, this is the first head-to-head comparison of these two tests evaluating T-cell-mediated immunity against SARS-CoV-2. In addition, we also evaluated humoral immunity in the same individuals using the in-house virus neutralization test and IgG ELISA assay. The evaluation yielded similar results for both IGRAs, with Quan-T-Cell appearing to be insignificantly (p = 0.08) more sensitive (all 90 individuals were at least borderline positive) than T-SPOT.COVID (negative results found in five patients). The overall qualitative (presence/absence of immune response) agreement of both tests with virus neutralization test and anti-S IgG was also excellent (close or equal to 100% in all subgroups, with the exception of unvaccinated Omicron convalescents, a large proportion of whom, i.e., four out of six subjects, were IgG negative while at least borderline positive for T-cell-mediated immunity measured by Quan-T). This implies that the evaluation of T-cell-mediated immunity is a more sensitive indicator of immune response than the evaluation of IgG seropositivity. This is true at least for unvaccinated patients with a history of being infected only by the Omicron variant, but also likely for other groups of patients.

High Incidence of SARS-CoV-2 Variant of Concern Breakthrough Infections Despite Residual Humoral and Cellular Immunity Induced by BNT162b2 Vaccination in Healthcare Workers: A Long-Term Follow-Up Study in Belgium.

To mitigate the massive COVID-19 burden caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several vaccination campaigns were initiated. We performed a single-center observational trial to monitor the mid- (3 months) and long-term (10 months) adaptive immune response and to document breakthrough infections (BTI) in healthcare workers (n = 84) upon BNT162b2 vaccination in a real-world setting. Firstly, serology was determined through immunoassays. Secondly, antibody functionality was analyzed via in vitro binding inhibition and pseudovirus neutralization and circulating receptor-binding domain (RBD)-specific B cells were assessed. Moreover, the induction of SARS-CoV-2-specific T cells was investigated by an interferon-γ release assay combined with flowcytometric profiling of activated CD4+ and CD8+ T cells. Within individuals that did not experience BTI (n = 62), vaccine-induced humoral and cellular immune responses were not correlated. Interestingly, waning over time was more pronounced within humoral compared to cellular immunity. In particular, 45 of these 62 subjects no longer displayed functional neutralization against the delta variant of concern (VoC) at long-term follow-up. Noteworthily, we reported a high incidence of symptomatic BTI cases (17.11%) caused by alpha and delta VoCs, although vaccine-induced immunity was only slightly reduced compared to subjects without BTI at mid-term follow-up.