SARS-CoV- 2 Omicron escapes vaccine-induced antibody neutralisation in patients with autoimmune inflammatory rheumatic diseases

ABSTRACT

Background: The question arises whether coronavirus disease 2019 vaccines can elicit cross-reactive antibody responses against the SARS-CoV- 2 Omicron variant in patients with autoimmune inflammatory rheumatic diseases (AIRDs). Method(s) This observational cohort study comprised 149 patients with AIRDs and 94 healthcare workers. 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 RBD-ACE2 binding inhibition assay. We assessed the incidence of breakthrough infections and the potential correlation with neutralising responses in participants after receiving third doses. Result(s) Although both the patients with AIRDs and healthcare workers showed robust neutralising responses against the wild-type virus (88.1 and 97.2%, respectively), the cross-neutralising responses against the Omicron variant were significantly lower in patients with AIRDs than in healthcare workers 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 the ancestral anti-spike immunoglobulin G titres. Within 6 weeks of immunologic assessments, significantly reduced Omicron-neutralising responses were detected in sera from patients with AIRDs 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% confidence interval, -0.559-[- 0.144], P = 0.001). Conclusion(s) Striking antibody evasion manifested by the Omicron variant in patients with AIRDs 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.