SARS-CoV-2 Omicron XBB.1 variant outbreak in a defined cohort: an epidemiological investigation incorporating longitudinal assessment of humoral response

Background: We describe an epidemiological investigation of a SARS-CoV-2-XBB.1 outbreak among healthcare workers (HCWs) returning from a 5-days educational tour abroad. Methods: We prospectively followed participants for symptoms and sampled blood for neutralization assays of four SARS-CoV-2 variants (wild type, XBB, EG.5.1, and BA.2.86) at 1, 3, and 6 months after their return. When available, samples from the 3 months preceding the outbreak were also tested. We compared geometric mean titers (GMT) of neutralizing antibodies of infected versus uninfected HCWs and febrile versus afebrile infected HCWs. Results: Nineteen (10%) of 181 HCWs were infected, all had mild COVID-19, 90% (17/19) had symptoms, and 16% (3/19) reported fever. Infected individuals tended to have lower pre-exposure XBB-neutralizing antibody titers (GMT of 32 versus 107 ID50, P = 0.248). Neutralization against XBB and newer subvariants peaked at 3 months and was higher among infected individuals (GMT 702 versus 156 [P < 0.001], 558 versus 163 [P = 0.001], and 558 vs. 182 [P = 0.002], ID50 for XBB, EG.5.1., and BA.2.86, respectively). By six months, these differences were no longer observed. Fever was positively associated with XBB neutralization (GMT 3474 versus 485, ID50 P = 0.005). Conclusions: Recently infected individuals are protected from reinfection with newer subvariants. However, protection is likely short lived.