The relationship between psychological stress and SARS-CoV-2 nucleocapsid-antibody response following natural infection: Longitudinal findings from the Aegis Study

Psychological stress can cause diminished immune response to infectious challenges. The extent this holds true during SARS-CoV-2 infection and the modifying effect of vaccination status is untested. We explored these relationships in a non-random sample standardized to the U.S. adult population. Across 2178 participants in the Aegis Study (2021-2022), we identified 507 eligible laboratory-confirmed SARS-CoV-2 infections. We estimated the natural log of nucleocapsid-binding antibody absorbance (N-antibody) at study visits up to 225 days following a positive SARS-CoV-2 test. Linear mixed effects models were fit to estimate the association of baseline perceived stress and, separately, allostatic load with N-antibody trajectories. Standardization was performed using iterative post-stratification weighting. Consistently, lower stress groups had higher N-antibody response. Low perceived stress was associated with greater antibody response up to 26 days post-positive test (P = 0.047) while low allostatic load was associated with greater antibody response up to 24 days (P = 0.049). Pre-infection vaccination modified the relationship between stress and N-antibody trajectories, where the observed relationships attenuated to the null for vaccinated individuals (P = 0.031). Overall, we found consistent evidence that high stress was associated with reduced N-antibody response following SARS-CoV-2 infection and that vaccination may narrow the antibody response across high versus low stress groups.