Cellular immune response to SARS-CoV-2 vaccination in SOTRs (n = 25) after the third dose of the mRNA vaccine (T0), and alternately, after the administration of the fourth booster dose (n = 15), or after the onset of the natural infection (n = 10). (A) T-cell responses (IFN-γ ELISpot SFC per 106 PBMC) to Spike were compared between T0 (white dots) and T1 (grey dots), respectively after the fourth dose (TxVac) or after natural infection (TxRec). Each dot plot represents the normalized mean spot count from duplicate wells (2.5 ± 0.5 × 105 PBMC/well) for each subject, after subtraction of the spot count of unstimulated cells. IFN-γ ELISpot > 112 SFC/106 PBMC were considered positive. Comparison of T-cell responses (IFN-γ ELISpot SFC per 106 PBMC) to Spike at T0 (B) and T1 (C) between TxVac and TxRec. (D) Correlation of T-cell responses (IFN-γ ELISpot SFC per 106 PBMC) to Spike against anti-SARS-CoV-2 IgG (BAU/mL) levels of both groups. (E) Correlation of T-cell responses (IFN-γ ELISpot SFC per 106 PBMC) to Spike against anti-SARS-CoV-2 S1 IgA (ratio) levels of both groups. The connection lines represent the antibody value of each subject at T0 and T1, while the dotted line corresponds to the threshold. The significances were determined using the Wilcoxon matched-pairs signed-rank test (two-tailed), Mann–Whitney test, and Spearman’s rank correlation (two-sided); ** p < 0.0021, *** p < 0.0002.