Humoral and cellular immunity in patients with rare autoimmune rheumatic diseases following SARS-CoV-2 vaccination

Gumber, Leher; Gomez, Nancy; Hopkins, Georgina; Tucis, Davis; Bartlett, Laura; Ayling, Kieran; Vedhara, Kavita; Steers, Graham; Chakravorty, Mithun; Rutter, Megan; Jackson, Hannah; Tighe, Patrick; Ferraro, Alastair; Power, Sheila; Pradère, Marie-Josèphe; Onion, David; Lanyon, Peter C.; Pearce, Fiona A; Fairclough, Lucy

Abstract

Objectives: COVID-19 vaccine responses in rare autoimmune rheumatic diseases (RAIRD) remain poorly understood, in particular there is little known about whether people develop effective T-cell responses. We conducted a prospective cohort study to evaluate the short-term humoral and cell-mediated T-cell response after the second SARS-CoV-2 vaccination in RAIRD patients compared to healthy controls (HC).

Methods: Blood samples were collected after the second dose and anti-spike, anti-nucleocapsid antibody levels and SARS-CoV-2 specific T-cell responses were measured and compared with HC. Activation induced marker and deep phenotyping assays were used to identify differences in T cells between high and low/no antibody groups, followed by multi-dimensional clustering.

Results: 50 patients with RAIRD were included (31 with AAV, 4 with other systemic vasculitis, 9 with SLE and 6 with myositis). Median anti-spike levels were significantly lower in RAIRD compared to HC (p<0.0001). 15 (33%) patients had undetectable and 26 (57%) had lower levels than the lowest HC. Rituximab in the last 12 months (p=0.003) was associated with reduced immunogenicity compared to a longer pre-vaccination period. There was a significant difference in B cell percentages (p=0.03) and spike-specific CD4+ T cells (p=0.02) between no/low antibody vs. high antibody groups. Patients in the no/low antibody group had a higher percentage of terminally differentiated (exhausted) T cells.

Conclusions: Following two doses, most RAIRD patients have lower antibody levels than the lowest HC and lower anti-spike T cells. RAIRD patients with low/no antibodies have diminished numbers and poor quality of memory T cells which lack proliferative and functional capacities.

Citation

Gumber, L., Gomez, N., Hopkins, G., Tucis, D., Bartlett, L., Ayling, K., Vedhara, K., Steers, G., Chakravorty, M., Rutter, M., Jackson, H., Tighe, P., Ferraro, A., Power, S., Pradère, M.-J., Onion, D., Lanyon, P. C., Pearce, F. A., & Fairclough, L. (2023). Humoral and cellular immunity in patients with rare autoimmune rheumatic diseases following SARS-CoV-2 vaccination. Rheumatology, 62(6), 2294-2303. https://doi.org/10.1093/rheumatology/keac574

• Journal Article Type: Article
• Acceptance Date: Sep 22, 2022
• Online Publication Date: Oct 17, 2022
• Publication Date: 2023-06
• Deposit Date: Sep 27, 2022
• Publicly Available Date: Oct 18, 2023
• Journal: Rheumatology
• Electronic ISSN: 1462-0324
• Publisher: Oxford University Press (OUP)
• Peer Reviewed: Peer Reviewed
• Volume: 62
• Issue: 6
• Pages: 2294-2303
• DOI: https://doi.org/10.1093/rheumatology/keac574
• Keywords: Pharmacology (medical); Rheumatology
• Public URL: https://nottingham-repository.worktribe.com/output/11747455
• Publisher URL: https://academic.oup.com/rheumatology/article/62/6/2294/6762096?login=false