Article Text
Abstract
Background Patients with primary Sjögren’s syndrome (pSS) worry about the effectiveness and safety of COVID-19 vaccination. pSS is characterized by B-cell hyperactivity, and previous influenza vaccination studies showed that pSS patients generate higher influenza-specific antibodies than healthy controls (HC).1,2 Furthermore, influenza vaccination resulted in elevated auto-antibody levels.1,2 Therefore, it is hypothesized that COVID-19 vaccination may also lead to a higher spike-specific antibody response.
Objectives To evaluate humoral and cellular immune response and adverse events (AEs) after COVID-19 vaccination in pSS patients compared to HC, and disease activity following vaccination in pSS patients. Furthermore, to evaluate change in spike-specific antibody levels in saliva and anti-SSA levels in serum following vaccination.
Methods In this prospective, longitudinal cohort study, pSS patients and HC were included in a 2:1 ratio. Participants received COVID-19 vaccinations following the Dutch vaccination programme. pSS patients did not use immunomodulatory drugs, except hydroxychloroquine (HCQ). Anti-spike 1 (S1) receptor binding domain (RBD) IgG serum antibody levels were measured 28 days after complete vaccination. AEs were collected 7 days after vaccination. Change in disease activity following vaccination was measured with EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) and EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI). In a subgroup of participants, spike-specific T-cell response was measured 7 days after complete vaccination with IFN-γ ELIspot. Definition of a T-cell responder was ≥2-fold increase in spot-forming cell (SFC) counts from pre- to post-vaccination and SFC counts of ≥50/106 cells in the post-vaccination sample. Salivary anti-S1 and anti-RBD antibodies and serological anti-SSA antibodies were also measured in this subgroup in pre- and post-vaccination samples (28 days after complete vaccination).
Results In total, 67 pSS patients and 33 HC were included. Of these, 47 (70%) and 14 (42%) received BNT162b2 (Pfizer-BioNtech), 13 (19%) and 5 (15%) received ChAdOx1 nCoV-19 (AstraZeneca), 6 (9%) and 8 (24%) received mRNA-1273 (Moderna), and 1 (1%) and 6 (18%) received Ad.26.COV2.S (Janssen), respectively. Overall, pSS patients were significantly older than HC, which was mainly due to the younger age in the Moderna and Janssen groups.
All participants had positive anti-SARS-CoV-2 antibody levels (>2500 AU/ml) post-vaccination. No differences in anti-SARS-CoV-2 antibody levels were observed between pSS patients and HC, for any of the vaccine types (Figure 1). Percentage of spike-specific T-cell responders was comparable between pSS patients (20/24, 83%) and HC (4/5, 80%). Salivary anti-SARS-CoV-2 IgG antibodies, but not IgA, increased post-vaccination in pSS patients (n=26) and HC (n=9). Salivary anti-RBD IgG antibodies were significantly correlated with serum anti-RBD antibodies (r= 0.597, p<0.001).
No serious AEs occurred. Frequencies of systemic AEs were comparable between pSS patients and HC (first vaccination: 34/67 (51%) vs. 16/33 (48%), p=0.83; second: 41/66 (62%) vs. 14/25 (56%), p=0.59). No significant worsening was observed in median ESSPRI (baseline: 6 (IQR 5-7), post-vaccination: 6 (4-7), p=0.16, n=64) and ESSDAI (baseline: 3 (IQR 1-4), post-vaccination: 2 (0-5), p=0.88, n=36). Furthermore, no increase in anti-Ro52 and anti-Ro60 antibody levels was seen (p=0.65 and p=0.58, respectively).
Conclusion pSS patients had similar humoral and cellular immune responses as HC, providing evidence that COVID-19 vaccination is effective in pSS patients. AEs were also comparable, and no increase in disease activity was seen in pSS patients, indicating COVID-19 vaccination is safe in pSS patients.
References [1]Brauner et al. Ann Rheum Dis 2017;76:1755-63.
[2]Bjork et al. Rheumatology 2020;59:1651-61.
Acknowledgements This work was funded by unrestricted grants of AstraZeneca and the Dutch Sjögren’s Patient Association (NVSP)
Disclosure of Interests Gwenny M. Verstappen: None declared, Liseth de Wolff: None declared, Suzanne Arends: None declared, Hella-Marie Heiermann: None declared, Yannick van Sleen: None declared, Annie Visser: None declared, Janneke H. Terpstra: None declared, Dimitri Diavatopoulos: None declared, Marieke van der Heiden: None declared, Arjan Vissink: None declared, Debbie van Baarle: None declared, Frans G.M. Kroese: None declared, Hendrika Bootsma Speakers bureau: Bristol-Myers Squibb, Novartis, Consultant of: Bristol-Myers Squibb, Roche, Novartis, Medimmune, Union Chimique Belge, Grant/research support from: Unrestricted grants from Bristol-Myers Squibb and Roche