Long-term dynamics of natural, vaccine-induced, and hybrid immunity to SARS-CoV-2 in a university hospital in Colombia: A cohort study

This prospective cohort study aimed to estimate the natural, vaccine-induced, and hybrid immunity to SARS-CoV-2, alongside the immunogenicity of the mRNA-1273 booster after the BNT162b2 primary series in healthcare workers in Colombia. IgG, IgA, and neutralizing antibodies were measured in 110 individuals with SARS-CoV-2 infection or a BNT162b2 primary series. Humoral responses and related factors were explored in a subgroup (n = 36) that received a BNT162b2 primary series followed by a mRNA-1273 booster (2BNT162b2 + 1mRNA-1273), and T-cell responses were evaluated in a subgroup of them (n = 16). For natural immunity, IgG and IgA peaked within three months, declining gradually but remaining detectable up to 283 days post-infection. Neutralizing antibody inhibition post-infection was below positive range (≥ 35%) but exceeded 97% in vaccine-induced and hybrid immunity groups. Following 2BNT162b2 + 1mRNA-1273, IgG peaked 3–4 months post-booster, gradually declining but remaining positive over 10 months, with IgA and neutralizing antibodies stable. Age and blood group were related to IgG response, while obesity and blood type to IgA response post-booster. Autoimmunity and blood type B were associated with lower neutralizing antibody inhibition. There were no differences in T-cell responses according to prior infection. These findings provide long-term insights into the immunity against SARS-CoV-2 and the immunogenicity of mRNA vaccines.