Fig. 4: Participants with LC demonstrate elevated levels of antibody responses to herpesviruses.

a, The REAP score distributions for SARS-CoV-2 S1 RBD between participants in the LC (n = 69) and CC (n = 10) groups with two doses of mRNA vaccine. Statistical significance was assessed using Wilcoxon rank-sum tests adjusted for multiple comparisons using the Benjamini–Hochberg method. b, The REAP score distributions for a given viral antigen between participants in the LC (n = 98) and pooled control (HC and CC, n = 38) groups. Statistical significance was assessed using Wilcoxon rank-sum tests adjusted for multiple comparisons using the Benjamini–Hochberg method. Only antigens with ≥2 individuals with LC and ≥2 control individuals with REAP score ≥ 1 were included. c, Seropositivity as assessed by SERA for EBV among participants with LC (n = 99) and control participants (n = 78). Significance was assessed using Fisher’s exact tests adjusted for multiple comparisons using the Benjamini–Hochberg method. d,e, REAP scores among EBV-seropositive individuals only for EBV p23 (d) and gp42 (e) by group. n = 25 (HC), n = 13 (CC), n = 98 (LC). f, SERA-derived z scores for the gp42 motif PVXF[ND]K among EBV-seropositive individuals only, plotted by group. The dashed line represents the z-score threshold for epitope positivity defined by SERA. n = 39 (HC), n = 38 (CC) and n = 80 (LC). g, Three-dimensional mapping of the LC-enriched linear peptide sequence PVXF[ND]K (magenta) onto EBV gp42 (purple) in a complex with gH (light grey) and gL (dark grey) (PDB: 5T1D). h, The relationship between the EBV gp42 PVXF[ND]K z score and the percentage of IL-4/IL-6 double-positive CD4⁺ T cells (of total CD4⁺ T cells) for participants. Only EBV-seropositive individuals were included. Correlation was assessed using Spearman’s correlation. The black line shows linear regression, and the shading shows the 95% CIs. n = 39 (HC), n = 38 (CC) and n = 80 (LC). i, The relationship between EBV p23 REAP score and the percentage of CD4⁺ T_EMRA cells (of total CD3⁺ T cells). Only EBV-seropositive individuals were included. Correlation was assessed using Spearman’s correlation. The black line depicts linear regression, and the shading shows the 95% CIs. Colours depict LCPS clusters as in Fig. 3. For the box plots, the central lines indicate the group median values, the top and bottom lines indicate the 75th and 25th percentiles, respectively, the whiskers represent 1.5× the interquartile range. Each dot represents one individual. Statistical significance of the difference in median values was determined using Kruskal–Wallis tests. Post hoc tests were performed using Dunn’s test with Bonferroni–Holm’s method to adjust for multiple comparisons. TM, transmembrane.