Endogenous Sex Hormones Explain Variation in Long-Term SARS-CoV-2 Antibody Persistence Beyond Biological Sex

Background: Sex-related differences in SARS-CoV-2 viral susceptibility, severity, and recovery are prevalent. Factors such as age and biological variation provide some explanation for immune response, yet the use of biological sex as a variable may limit understanding of underlying individual mechanisms related to endocrine–immune function involved in long-term immune memory. Endogenous sex hormone concentrations provide a means to assess the magnitude or durability of antibody persistence and disease recovery. Objective: This study examined salivary concentrations of 17β-estradiol and testosterone, as well as the number of weeks since prior SARS-CoV-2 viral infection. The study aimed to determine whether endogenous sex hormones contributed additional explanatory value to antibody persistence beyond biological sex. Methods: A cross-sectional study included 75 college students (63% female) who reported weeks since previous SARS-CoV-2 infection (M = 15.41, SD = 7.13), confirmed through a positive SARS-CoV-2 anti-N rapid antibody test. Participants provided saliva samples, which were tested for concentration of 17β-estradiol and testosterone. Hierarchical multiple regression analyses examined the effects of biological sex and endogenous sex hormones on the persistence of SARS-CoV-2 antibodies following natural infection. Results: 17β-estradiol was the strongest positive predictor of SARS-CoV-2 antibody persistence (β = 0.63, p < 0.001). Departing from previous findings, biological sex was not a significant predictor of antibodies targeting the SARS-CoV-2 N protein. Conclusions: Findings underscored the role of estradiol on immune recovery in a healthy young adult population. Individual hormone variation appears more informative than sex classification for understanding antibody persistence and immune response.