Determinants of protection against SARS-CoV-2 Omicron BA.1 and Delta infections in fully vaccinated outpatients (preprint)

ABSTRACT

We aimed to evaluate the association between the humoral and cellular immune responses and symptomatic SARS-CoV-2 infection with Delta or Omicron BA.1 variants in fully vaccinated outpatients. Anti-RBD IgG levels and IFN-{gamma} release were evaluated at PCR-diagnosis of SARS-CoV-2 in 636 samples from negative and positive patients during Delta and Omicron BA.1 periods. Median levels of anti-RBD IgG in positive patients were significantly lower than in negative patients for both variants (p < 0.05). The risk of Delta infection was inversely correlated with anti-RBD IgG titres (aOR = 0.63, 95% CI [0.41; 0.95], p = 0.03) and it was lower in the hybrid immunity group compared to the homologous vaccination group (aOR = 0.22, 95% CI [0.05; 0.62], p = 0.01). In contrast, neither the vaccination scheme nor anti-RBD IgG titers were associated with the risk of BA.1 infection in multivariable analysis. IFN-{gamma} release post-SARS-CoV-2 peptide stimulation was not different between samples from patients infected (either with Delta or Omicron BA.1 variant) or not (p = 0.77). Our results show that high circulating levels of anti-RBD IgG and hybrid immunity were independently associated with a lower risk of symptomatic SARS-CoV-2 infection in outpatients with differences according to the infecting variant.