Humoral Immune Response to Inactivated SARS-CoV-2 Vaccine in Populations With and Without Prior COVID-19 Infection: A Longitudinal Cohort Study

To assess the dynamics of humoral immune responses to inactivated SARS-CoV-2 vaccines across populations with and without prior COVID-19 infection, a longitudinal cohort study was conducted. A total of 38 COVID-19-recovered individuals and 165 naïve participants (without prior COVID-19 infection) were enrolled, all of whom completed a two-dose vaccination regimen. Levels of anti-spike (anti-S) and anti-nucleocapsid (anti-N) antibodies were analyzed at baseline and post-vaccination time points, including 6 weeks post-first dose, and 1 month and 6 months post-second dose. Among naïve participants, the seropositivity rate for anti-S antibodies increased to 96.23% at 1 month after the second dose with anti-S titers peaking at a median of 54.59 U/mL (<i>p</i> < 0.0001). Conversely, COVID-19-recovered participants exhibited significantly elevated anti-S levels after the first dose (median titer: 637.70 U/mL, <i>p</i> < 0.0001), with no notable changes following the second dose. Anti-S levels in both groups declined by 6 months post-second dose. The dynamic pattern of anti-N antibodies was comparable to that of anti-S, albeit with weaker vaccine-induced responses. Notably, levels of both anti-S and anti-N antibodies decreased with advancing age (<i>p</i> < 0.001). Males demonstrated lower anti-N antibody levels compared with females (<i>p</i> = 0.038), while the presence of underlying diseases was associated with higher anti-S antibody levels (<i>p</i> = 0.030). In conclusion, two doses effectively augmented antibody levels in naïve individuals, whereas a single dose may suffice to confer immune protection in COVID-19-recovered individuals. Antibody levels wane over time, necessitating further investigations into the durability of vaccine-mediated immune protection, evidence-based recommendations for preventive vaccination, and the formulation of immunization strategies tailored to distinct populations.