Cross-sectional assessment of T cellular SARS-CoV-2 immunity following a fourth COVID-19 vaccination using a whole blood-based IFNg release assay

Question

In addition to innate immunity, adaptive immunity, i.e. T and B cells substantially contribute to the control of viral infections with e.g. SARS-CoV-2. Interferon-gamma (IFNγ) serves a central function in T cell-mediated immunity. To date, a limited number of studies have investigated the factors influencing T cell reactivity to SARS-CoV-2 in exposed, COVID-19-vaccinated, healthcare workers (HCWs).

Methods

For this cross-sectional analysis, as part of the longitudinal CoVacSer study, blood samples with a paired study questionnaire were collected in September 2023 from 113 HCWs who had already received at least four COVID-19 vaccinations. T cell reactivity was assessed using the Elecsys® IFNγ Release Assay (IGRA), for which a SARS-CoV-2 peptide mix was used as Antigen (Ag) to stimulate T cells. A negative control (NC) without Ag was used to determine background release of IFNγ. The T cell reactivity was assessed by calculating Ag-NC in IU/ml. Additionally, anti-SARS-CoV-2-Spike IgG levels were measured using an Enzyme-linked Immunosorbent Assay (ELISA).

Results

The T-cell reactivity analysed in the study showed a median of 0.75 Ag-NC (IU/ml) [IQR: 0.32-1.28 Ag-NC (IU/ml)]. Univariate analyses showed that T-cell reactivity was significantly higher in individuals who had been infected at least once (p=0.049), had no regular patient contact (p=0.005), or were non-smokers (p=0.026). No significant difference was found for gender (p=0.645). IgG levels (r=0.152, p=0.110), age (r=-0.174, p=0.855), and BMI (r=0.110, p=0.248) were nor significantly correlated with T-cell reactivity. Infection was identified as the only significant influencing factor in a multivariable regression including the variables age, BMI, smoking, infection and patient contact (p=0.044).

Conclusion

As expected, past infection with SARS-CoV-2 was associated with increased T-cell reactivity. HCWs without regular patient contact showed a higher T-cell reactivity because the number of infections was higher in this group. Lower T-cell activity in smokers was probably caused by a combination of slightly lower T-cell responses after vaccination and the lower SARS-CoV-2 infection rate.