Objectives People with immune-mediated inflammatory diseases (IMIDs) may be more vulnerable to severe COVID-19 outcomes. COVID-19 vaccination is a key element in mitigating this risk. Anti-SARS-CoV-2 antibodies (Ab), including anti-spike (S) and anti-receptor binding domain (RBD) Ab, are metrics of seroconversion following COVID-19 vaccination in the general population. We assessed if anti-S and anti-RBD antibodies were negatively correlated with COVID-19 infection in IMID. Methods SUCCEED, a prospective Canada-wide study, was conducted in 2 phases. First, between Feb 2021-Jul 2023, adult IMID participants provided dried blood spot samples for anti-S and anti-RBD ELISA testing at intervals of 1, 3, 6, and 12 months following each COVID-19 vaccine dose. Second, between Sep 2022-Aug 2023, consenting participants from 4 academic centers in British Columbia, Ontario and Quebec (2) also provided monthly saliva samples for PCR detection of SARS-CoV-2. We studied subjects receiving at least their primary series (3+ doses) of a COVID-19 vaccine. Multivariable general estimating equation (GEE) models (accounting for repeated measures) evaluated PCR SARS-CoV-2 detection in saliva, assessing the effects of anti-S or anti-RBD levels (in separate models) within the 6 months preceding a given saliva sample. We controlled for recent COVID-19 infection, sex, age, medications (conventional immunosuppressives, biologics, and prednisone), and time since last COVID vaccine. Results 366 participants contributed 1,266 saliva samples. Participants were 79.8% female and 85.5% White, with median age 56.7 (standard deviation: 13.8) years. Most participants were taking immunosuppressants (N=252, 68.9%). The majority (N=356, 97.3%) of participants displayed seroconversion at the first saliva sample, defined as ≥11.3 Binding Antibody Units (BAU)/ml for anti-S or ≥31 BAU/ml for anti-RBD. In the GEE models of positive saliva PCR for SARS-CoV-2, (Table 1) a 1000 BAU/ml increase in anti-S was associated with an adjusted odds ratio (aOR) of 0.66 (95% confidence interval [CI] 0.45-0.97). Anti-RBD Ab levels had a similar effect (aOR 0.91, 95% CI 0.81-1.02). Table 1: Odds Ratios, OR (95% confidence intervals, CI) for Having a Positive COVID-19 Saliva Test in Univariable and Multivariable GEE Models Conclusion In this large, multi-center sample of COVID-19-vaccinated individuals with IMIDs, most of whom were immunosuppressed, we demonstrated that anti-S Ab levels were associated with lower odds of positive saliva PCR test for SARS-CoV-2, with a similar trend for anti-RBD Ab. This highlights clear benefits for vaccination against SARS-CoV-2 in IMID.