Effect of Distress, Anxiety, and Depressive Symptoms on SARS-CoV-2 mRNA BNT162b2 Vaccine Efficacy in Cancer Patients

Background/Objectives: Our previous study of 291 cancer patients, we showed that 20% did not respond to two doses of COVID-19 vaccine administered six weeks apart. Methods: Here, we investigated if psychological factors (distress, anxiety, and depressive symptoms) affected antibody response and markers of vaccine activation (D-dimer) after 6 months from initial vaccination. Results: Overall, 31 subjects (14.2%) had no antibody response at 6 months. Our analysis revealed significant predictors of vaccine failure, including the stage of metastatic disease and high-stress levels (OR = 2.46, 95% CI, 1.05–5.77, p = 0.04). Notably, nonresponders showed twice the prevalence of distress than responders (21% vs. 10%, p = 0.04). Longitudinal measurements of IgG levels indicated that participants with high depressive symptoms at baseline maintained lower antibody levels over six months (p = 0.003). In addition, women with high anxiety showed reduced levels of D-dimer at 6 months (p = 0.03). These data also showed that smokers and former smokers had significantly lower antibody levels than their nonsmoking counterparts (p = 0.0004). At baseline, the high discomfort rate (≥5) was 34.4% in women and 23.8% in men; only men experienced an increase in median discomfort during the observation period. Moreover, a higher educational level was related to increased distress among women (p = 0.046). Conclusions: These findings underscore a critical association between elevated psychological distress and reduced immune responses to the COVID-19 vaccine, emphasizing the urgent need for targeted psychological and behavioral support within this vulnerable population.