Vaccine response against SARS-CoV-2 in patients with primary Sjögren*s syndrome

Patients with autoimmune rheumatic diseases, including primary Sjögren*s
syndrome (pSS), worry about their risk of COVID-19 infection and also about the
effectiveness and potential side effects of vaccination. Reasons for concern
are an imbalance of the immune system (e.g., lymphopenia), relatively frequent
use of immunosuppressive drugs, and sometimes severe organ manifestations
(e.g., interstitial lung disease, tubulointerstitial nephritis). On the other
hand, patients with pSS generally have an over-active immune system,
characterized by B cell hyperactivity. In line with this notion, previous
studies have shown that pSS patients obtain higher antibody titers after
influenza vaccination compared with controls. Not only influenza-specific
antibodies increased, but there were indications of polyclonal B cell
activation after vaccination evidenced by higher titers of anti-EBV and
autoantibody titers. Based on these findings, we speculate that pSS patients
can develop a strong humoral response to SARS-CoV-2 after vaccination. However,
polyclonal B cell activation may also cause potential side effects of
vaccination. Monitoring of the SARS-CoV-2 vaccination response in pSS will
provide important information on efficacy and safety of vaccination in this
patient group. Furthermore, an in-depth study of immune cell composition in
relation to antibody titers could provide important insights into the
mechanisms of B cell hyperactivity in pSS.

The primary objective is to study protective antibody responses after
SARS-CoV-2 vaccination in patients with pSS. Secondary objectives are
monitoring of adverse events and disease activity after vaccination, studying
the prognostic value of anti- SARS-CoV-2 antibodies in saliva and in-depth
analysis of the adaptive immune response to SARS-CoV-2 vaccination in pSS
patients, compared to healthy individuals.

Prospective, single-centre, longitudinal cohort study.

The vaccine will be administered two times with an interval specified by the
manufacturer (or by the health care provider). At baseline and day 28 after the
second vaccination, participants will collect a blood sample at home with a
finger prick. A subgroup of participants will have to visit the hospital at two
time points for blood donation. In these participants blood will be drawn prior
to both vaccinations and at day 7 after the second vaccination (160 mL in
total). Blood sampling will give minor discomfort. Vaccination can cause AEs
associated with the immune response, including fatigue, chills, headache,
myalgia, and pain at the injection site. For seven days after each vaccination,
participants will be asked to record local and systemic reactions using a
questionnaire. At baseline and at 28 days, 3, 6, and 12 months after
vaccination, participants will be asked to complete questionnaires about
corona-related symptoms, potential subsequent testing for SARS-CoV-2, diagnosis
of COVID-19, and severity of COVID-19. At the same time points, patients will
be asked to complete questionnaires about their disease activity.

This study will collect information on immune response and adverse events after
vaccination against COVID-19 in a vulnerable patient cohort. Understanding the
ability to mount a protective immune response after vaccination will help to
counsel patients during the pandemic. Furthermore, an in-depth study of immune
cell composition in relation to antibody titers could provide important
insights into the mechanisms of B cell hyperactivity in pSS.