Article Text
Abstract
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.
- Covid-19
- Vaccination
- Antirheumatic Agents
- Autoimmune Diseases
Data availability statement
The data that support the findings of this study are available from the corresponding authors on reasonable request.
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Data availability statement
The data that support the findings of this study are available from the corresponding authors on reasonable request.
Footnotes
W-JK and S-HC are joint first authors.
Handling editor Josef S Smolen
Contributors Concept and clinical protocol development: S-HC, J-SS, JYP, J-WC and STC. Accrual of patients and data collection: J-WC and STC. Experimental design and data analysis: W-JK, S-HC, J-WC and STC Original draft of the manuscript: W-JK and S-HC. Critical review of the manuscript: J-WC and STC. Responsibility for the overall content as guarantor: J-WC and STC.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
Provenance and peer review Not commissioned; externally peer reviewed.
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