SARS-CoV-2 Omicron escapes mRNA vaccine booster-induced antibody neutralisation in patients with autoimmune rheumatic diseases: an observational cohort study.

OBJECTIVES:This study investigates whether COVID-19 vaccines can elicit cross-reactive antibody responses against the Omicron variant in patients with autoimmune rheumatic diseases (ARDs). METHODS:This observational cohort study comprised 149 patients with ARDs and 94 healthcare workers (HCWs). Blood samples were obtained at enrolment, a median of 15 weeks after the second vaccine dose or 8 weeks after the third dose. The functional cross-neutralisation capacity of sera was measured using the Omicron variant receptor-binding domain-ACE2 binding inhibition assay. We assessed the incidence of breakthrough infections and the potential correlation with neutralising responses in participants after receiving third doses. The association of time-from-vaccine and neutralising responses in sera was predicted using linear regression analysis. RESULTS:The mean cross-neutralising responses against the Omicron variant developed after the second dose was 11.5% in patients with ARDs and 18.1% in HCWs (p=0.007). These responses were significantly lower in patients with ARDs than in HCWs after the third dose (26.8% vs 50.3%, p<0.0001). Only 39.2% of the patient sera showed functional neutralisation capacity to the Omicron variant and cross-neutralising responses were shown to be poorly correlated with anti-spike immunoglobulin G titres. Within 6 weeks of immunological assessments, significantly lower Omicron-neutralising responses were detected in sera from patients with ARDs who developed breakthrough infections compared with those who did not (p=0.018). Additionally, a relative decline was implied in neutralising responses against the Omicron variant as a reference to the wild-type virus during 120 days since the third vaccination, with a predicted decay rate of -0.351%/day (95% CI, -0.559 to -0.144, p=0.001). CONCLUSIONS:Striking antibody evasion manifested by the Omicron variant in patients with ARDs and current vaccine-induced immunity may not confer broad protection from Omicron breakthrough infection, highlighting the need for further research on vaccine effectiveness in patients with immune dysfunctions.