Determinants of protection against SARS‐CoV‐2 Omicron BA.1 and Delta infections in fully vaccinated outpatients.

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‐receptor binding domain (RBD) IgG levels and interferon‐gamma (IFN‐γ) 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 frequency of Omicron BA.1 infection in patients with anti‐RBD IgG concentrations ≥1000 binding antibody units (BAU)/mL was 51.0% and decreased to 34.4% in patients with concentrations ≥3000 BAU/mL. For Delta infection, the frequency of infection was significantly lower when applying the same anti‐RBD IgG thresholds (13.3% and 5.3% respectively, p < 0.05). In addition, individuals in the hybrid immunity group had a 4.5 times lower risk of Delta infection compared to the homologous vaccination group (aOR = 0.22, 95% CI: [0.05−0.64]. No significant decrease in the risk of Omicron BA.1 infection was observed in the hybrid group compared to the homologous group, but the risk decreased within the hybrid group as anti‐RBD IgG titers increased (aOR = 0.08, 95% CI: [0.01−0.41], p = 0.008). IFN‐γ 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 > 0.05). 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 (www.clinicaltrials.gov; ID NCT05060939). [ABSTRACT FROM AUTHOR]