First evidence of an association between alexithymia and reduced humoral immunity following COVID-19 vaccination, independent of insomnia and metabolic factors in healthcare workers

Introduction Psychological factors have been increasingly implicated in immune regulation; however, the role of emotional awareness in shaping vaccine responses remains unexplored. Alexithymia, characterized by the difficulty in identifying and describing emotions, represents a psychosomatic construct associated with chronic stress physiology and immune dysregulation. This study investigated for the first time whether alexithymia, alongside other psychological factors, is associated with vaccine-induced humoral immunity, especially serum SARS-CoV-2 anti-Spike (anti-S) IgG concentrations following vaccination. Methods In this cross-sectional study, 198 healthcare workers who received the BNT162b2 mRNA vaccine were evaluated 4–6 months post-vaccination. Alexithymia was assessed using the Toronto Alexithymia Scale-20 (TAS-20), insomnia using the Athens Insomnia Scale, and anxiety/depression using Hamilton scales. Self-reported positive thinking was also assessed. Anti-S IgG concentrations against the receptor-binding domain (RBD) of the S1 subunit were quantified, and multivariable linear regression (stepwise method) analyses were performed adjusting for demographic, metabolic, inflammatory, and behavioral covariates. Results Higher alexithymia (p = 0.002) and insomnia scores (p < 0.001) were independently associated with lower anti-S IgG concentrations after adjustment for vaccination doses, prior COVID-19 infection, BMI, interleukin-6 (IL-6), smoking, and alcohol consumption. Among alexithymia subscales, difficulty identifying and difficulty describing feelings, but not externally oriented thinking, were inversely associated with anti-S IgG concentrations. Participants who reported post-vaccination fever exhibited higher anti-S IgG concentrations and lower alexithymia scores; this retrospective finding is exploratory and does not establish a difference in inflammatory activation. Conclusion Alexithymia and insomnia are independently associated with lower anti-S IgG concentrations in healthcare workers. Although these concentrations correlate with neutralizing activity, neutralization and clinical protection were not directly assessed in this study. Nevertheless, these findings suggest that alexithymia may represent an underrecognized psychosomatic correlate of post-vaccination antibody responses, meriting further investigation as a potential marker of variation in vaccine responses and protection. Prospective studies should determine whether the observed association extends to neutralizing activity or clinical protection.