Dear Editor,
Despite a substantial reduction in humoral immunity, COVID-19 vaccines still show robust protection against severe COVID-19 disease, even against highly mutated variants.1, 2 Accumulating evidence suggests that T cell response plays a key role in the protection against severe disease (i.e., hospitalization and death).1, 3, 4 Two recent papers published in Journal of Infection5, 6 found that the cellular immunity as assessed with an interferon gamma (IFNγ) release assay (IGRA) declined progressively 6–12 months after full vaccination with various COVID-19 vaccines, especially in those with no history of SARS-CoV-2 infection. In the present study, we would like to confirm these findings and to show the impact of the second booster administration on the cellular immunity; a feature not explored in the two above-mentioned studies.
On September 2022, 54 participants of the CRO-VAX-HCP study7 received the second and bivalent adapted BNT162b2 booster. Forty were females (median age = 51.0 years; IQR = 43.3–58.8) and 14 were males (median age = 52.5 years; IQR = 43.8–59.8). Age was not different between females and males (p = 0.60, Man-Whitney test). Most of the participants (45/54; 83.3%) had a history of SARS-CoV-2 infection. Blood was collected in lithium heparin and serum separator tubes (BD Vacutainer, Becton Dickinson, New Jersey, USA) just before and 28 days after the booster administration. The study was approved by a central ethical committee (CHU UCL Namur, Yvoir, Belgium; approval number: 2020-006149-21). Total antibodies against the NCP (Roche Diagnostics) were measured using the Elecsys Anti-SARS-CoV-2 assay. Results above 1.0 cut-off index (COI) were considered positive and indicate a previous SARS-CoV-2 infection. Moreover, the T cell-mediated immune response was assessed using the cobas IGRA SARS-COV-2 Tubes and the Elecsys IGRA SARS‑CoV‑2 assay (Roche Diagnostics). The test measures the release of interferon gamma (IFNγ) from T cells in response to an in vitro SARS-CoV-2 stimulation in whole blood samples which have been formerly in contact with SARS-CoV-2 coated antigens.8 Median and interquartile range (IQR) were used to present the data. A Mann-Whitney test was used to assess the impact of the second booster on cellular immunity. A multiple comparison test was used to evaluate the effect of anti-NCP levels on the cellular immunity. Results were categorized as<1.0 COI, 1.0–10.0$8COI and>10.0 COI. A Spearman correlation was also performed for the comparison between anti-NCP and IFNγ. Statistical analyses were performed using GraphPad Prism 9.5.1 (GraphPad Software, Massachusetts, USA). p<0.05 was considered statistically significant.
Before the second booster administration, we found a significant and positive correlation between anti-NCP and IFNγ (r = 0.39 (95%CI = 0.11–0.61), p = 0.005). Individuals with negative anti-NCP had significantly lower levels of IFNγ as compared to individuals with high anti-NCP, i.e.>10.0 COI (INFγ level of 0.18 versus 1.00 IU/mL, p = 0.007). These data are consistent with those published by Bonnet et al. and Pighi et al.5, 6 One month after the bivalent booster administration, a significant increase in IFNγ was only observed for individuals with no history of SARS-CoV-2 infection (from 0.18 to 0.51 IU/mL, fold-increase = 2.85, p = 0.04). Mean fold increase 28 days after the bivalent booster in individuals with positive anti-NCP was close to 1 (i.e., 1.09 and 1.02) ( Table 1 and Fig. 1). Additionally, the correlation between anti-NCP and IFNγ was no longer significant after the second booster administration (r = 0.14 (−0.14 to 0.40), p = 0.30).
Table 1.
INFγ levels before and after the bivalent booster in subjects with low (<1.0 COI), intermediate (1–10 COI) and high (>10 COI) anti-NCP antibodies.
| Anti-NCP (COI) | Before booster | After booster | Fold-increase | P value |
|---|---|---|---|---|
| <1 (n = 9) |
0.18 IU/mL 95%CI: 0.08–0.90 |
0.51 IU/mL 95%CI: 0.33–1.87 |
2.85 | 0.04 (*) |
| 1–10 (n = 21) |
0.63 IU/mL 95%CI: 0.36–0.73 |
0.69 IU/mL 95%CI: 0.40–1.6 |
1.09 | 0.22 (ns) |
| >10 (n = 24) |
1.00 IU/mL 95%CI: 0.48–2.30 |
1.02 IU/mL 95%CI: 0.60–1.93 |
1.02 | 0.97 (ns) |
Fig. 1.
Comparison of INFγ levels before and after the bivalent booster in subjects with low (<1.0 COI), intermediate (1–10 COI) and high (>10 COI) anti-NCP antibodies. Results were only statistically different before booster administration between subjects with low and high anti-NCP antibodies.
Based on these findings, we confirm that individuals with no history of SARS-CoV-2 infection presented a reduced cellular immunity but were those that were more susceptible to benefit from a second booster in terms of cellular immunity. These findings need to be confirmed in other studies with a larger population.
Funding
None declared.
Ethical approval
The study was approved by a central ethical committee (CHU UCL Namur, Yvoir, Belgium; approval number: 2020-006149-21).
Informed consent
All subjects recruited provided written informed consent for participation.
Author contributions
All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
None.
References
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