Antibody response to four doses of SARS-CoV-2 vaccine in rare autoimmune rheumatic diseases: an observational study

Leher Gumber; Hannah Jackson; Nancy Gomez; Georgina Hopkins; Davis Tucis; Mithun Chakravorty; Patrick Tighe; Matthew J Grainge; Megan Rutter; Alastair Ferraro; Sheila Power; Marie-Josèphe Pradère; Peter C Lanyon; Fiona A Pearce; Lucy Fairclough

doi:10.1093/rap/rkad097

Antibody response to four doses of SARS-CoV-2 vaccine in rare autoimmune rheumatic diseases: an observational study

Rheumatol Adv Pract. 2023 Nov 11;7(3):rkad097. doi: 10.1093/rap/rkad097. eCollection 2023.

Authors

Leher Gumber^{1

2}, Hannah Jackson³, Nancy Gomez³, Georgina Hopkins³, Davis Tucis³, Mithun Chakravorty¹, Patrick Tighe³, Matthew J Grainge², Megan Rutter^{1

2}, Alastair Ferraro⁴, Sheila Power⁵, Marie-Josèphe Pradère⁵, Peter C Lanyon^{1

2

6}, Fiona A Pearce^{1

2

6}, Lucy Fairclough³

Affiliations

¹ Department of Rheumatology, Nottingham University Hospitals NHS Trust, Nottingham, UK.
² Lifespan and Population Health, School of Medicine, University of Nottingham, Nottingham, UK.
³ School of Life Sciences, University of Nottingham, Nottingham, UK.
⁴ Department of Nephrology, Nottingham University Hospitals NHS Trust, Nottingham, UK.
⁵ Research & Innovation, Nottingham University Hospitals NHS Trust, Nottingham, UK.
⁶ NIHR Nottingham Biomedical Research Centre, Nottingham, UK.

Abstract

Objective: Antibody responses to coronavirus disease 2019 (COVID-19) vaccines are reduced among immunocompromised patients but are not well quantified among people with rare disease. We conducted an observational study to evaluate the antibody responses to the booster SARS-CoV-2 vaccine in people with rare autoimmune rheumatic diseases (RAIRD).

Methods: Blood samples were collected after second, before third, after third and after fourth vaccine doses. Anti-spike and anti-nucleocapsid antibody levels were measured using an in-house ELISA. Logistic regression models were built to determine the predictors for non-response. Results were compared with age- and sex-matched healthy controls.

Results: Forty-three people with RAIRD were included, with a median age of 56 years. Anti-spike seropositivity increased from 42.9% after second dose to 51.2% after third dose and 65.6% after fourth dose. Median anti-spike antibody levels increased from 33.6 (interquartile range 7.8-724.5) binding antibody units after second dose to 239.4 (interquartile range 35.8-1051.1) binding antibody units after the booster dose (third dose, or fourth dose if eligible). Of the participants who had sufficient antibody levels post-second dose, 22.2% had insufficient levels after the booster, and 34.9% of participants had lower antibodies after the booster than the lowest healthy control had after the second dose. Rituximab in the 6 months prior to booster (P = 0.02) and non-White ethnicity (P = 0.04) were associated with non-response. There was a dose-response relationship between the timing of rituximab and generation of sufficient antibodies (P = 0.03).

Conclusion: Although the booster dose increased anti-spike IgG and seropositivity rates, some people with RAIRD, particularly those on rituximab, had insufficient antibody levels despite three or four doses.

Keywords: SARS-CoV-2; antibody; rare autoimmune rheumatic diseases; rituximab; vaccination.