To the Editor:
Vaccination is essential in controlling the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The increased risk of severe COVID-19 infection in patients with inflammatory rheumatic diseases (IRDs) makes vaccination particularly relevant in this population.1 Data are scarce regarding immunogenicity of SARS-CoV-2 vaccines in axial spondyloarthritis (axSpA). Most of the studies had a short-term follow-up period and focused on cohorts of mixed IRD patients or patients who received mRNA vaccines, showing an impaired immunogenicity in these patients relative to healthy controls with lower anti–SARS-CoV-2 spike-specific IgG antibodies (anti-S Ab) levels.2,3,4,5,6 We aimed to prospectively evaluate the vaccine responsiveness in a homogeneous monocentric Belgian cohort of patients with axSpA. This study, conducted between June and October 2021, complied with the Declaration of Helsinki and was approved by the local ethics committee (P2021/307 SRB2021130). Written informed consent was obtained from all patients.
Patients (aged ≥ 18 yrs) with axSpA according to the Assessment of Spondyloarthritis international Society classification criteria followed in our department without any history of COVID-19 infection (negative for PCR, antibodies, or high clinical suspicion based on history) who were fully vaccinated against SARS-CoV-2 (2 doses of mRNA vaccines or ChAdOx1 nCoV-19, or 1 dose of Ad26.COV2.S) were invited to participate. Vaccination was done on a voluntary basis, independently of the study. We did not vaccinate our patients as part of the study; we only studied their serologies if they had chosen to be vaccinated. Demographic and clinical characteristics, as well as axSpA-specific data, were collected from medical records. The humoral immune response of vaccination was evaluated by measuring the anti-S Ab levels at 1 month (36.8 days ± SD 8.8) and 3 months (96.1 days ± SD 9.8) after complete vaccination using the LIAISON SARS-CoV-2 TrimericS IgG (DiaSorin) assay. Data were presented as percentage for qualitative variables and as median (range) for nonnormally distributed data. We used the Wilcoxon-Mann-Whitney test (paired samples), Mann-Whitney nonparametric test (continuous variables), and Spearman correlation test as appropriate. P < 0.05 was considered statistically significant.
A total of 36 patients were included (median age 47 yrs, 47.2% females, median axSpA disease duration 11 yrs, 91.7 % fulfilled the New York criteria), of whom 27 patients were on immunosuppressive therapy (25 patients on anti–tumor necrosis factor [TNF] and 2 patients on anti–interleukin-17 biologic therapy, all in monotherapy; Table 1). No patient was taking corticosteroids. Twenty-six patients (72.2%) were vaccinated with mRNA vaccine (22 [61.1%] with BNT162b2 and 4 [11.1%)] with mRNA-1273). Ten patients (27.8%) were vaccinated with viral vector vaccine (9 [25%] with ChAdOx1 nCoV-19, and 1 [2.8%] with Ad26.COV2.S vaccine). No patient had their treatment for the inflammatory disease changed in the perivaccination period.
Demographic and clinical characteristics.
The patients were stratified into 2 groups according to their treatment: 9 (25%) patients without immunosuppression vs 27 (75%) patients with immunosuppression. Both groups were similar except for an overrepresentation of females in the group without immunosuppression (77.8% vs 37%). Anti-S Ab were detected in 35/36 (97.2%) patients at 1 month and 33/36 (91.7%) patients at 3 months. One patient, a man aged 67 years with skin psoriasis and ≥ 2 comorbidities who was treated with infliximab, was a nonresponder. Two patients (56 and 67 years old, both under anti-TNF biologic therapy) dropped their antibody levels below the positivity threshold at 3 months. Antibody levels decreased significantly between 1 and 3 months (P < 0.0001) without any significant statistical difference between the 2 groups. At 1 month, anti-S Ab levels in the subgroup vaccinated with mRNA vaccines was significantly higher in patients without immunosuppression compared to the group on immunosuppression (2940 binding antibody units (BAU)/mL vs 1410 BAU/mL, P = 0.04). Both at 1 and 3 months, the patients vaccinated with mRNA vaccine had significantly higher median anti-S Ab titers compared to patients vaccinated with a viral vector vaccine (median 1635 BAU/mL vs 208 BAU/mL at 1 month, P < 0.0001; and 560 BAU/mL vs 121.8 BAU/mL at 3 months; P = 0.007; Figure 1). The drop of antibody levels between 1 and 3 months was also significantly greater with mRNA vaccines compared to viral vector vaccines (median difference 996.5 BAU/mL for mRNA vaccine vs 112.2 BAU/mL for non-mRNA vaccine; P < 0.0001). There was no difference in humoral response between the 2 mRNA vaccines. During this study of short term follow-up after SARS-CoV-2 vaccination, no patient reported a symptomatic COVID-19 infection. This study is limited by the absence of a control group, the small size of the cohort, and the low median age of the participants.
Antibody levels depending on the type of vaccine. Anti–SARS-CoV-2 antibody levels in binding antibody units (BAU)/mL after complete vaccination in patients with axial spondyloarthritis at 1 month (left panel) and 3 months (right panel) depending on the type of vaccine received.
We conclude that the main factor influencing anti–SARS-CoV-2 spike-specific IgG antibody levels in patients with axSpA is the type of vaccine rather than the patient’s level of immunosuppression, although the maintenance of the biologic therapy during the perivaccination period could be a potential confounder. While antibody levels persisted 3 months after complete vaccination in the majority of patients, the rapid decrease in these levels is an argument for an additional vaccine dose in the upcoming months in this population. The effect of this additional vaccine dose needs to be investigated.
Footnotes
The authors declare no conflicts of interest relevant to this article.
- Copyright © 2022 by the Journal of Rheumatology
