Chief Medical Informatics Officer Illumination Health, United States
Background: Given possible increased risk of COVID-19 in patients with autoimmune conditions, we must better understand the immunogenicity and safety of SARS-CoV-2 vaccines in people living with rheumatic disease. We are conducting the Covid VaccinE Response (COVER) trial, a multicenter, randomized controlled trial to determine response to SARS-CoV-2 booster in rheumatology patients on immunomodulatory therapies.
Objectives: We examined response to prior vaccine doses (primary mRNA vaccine series or booster) in relation to the time since vaccination and therapy.
Methods: The parent COVER trial randomizes rheumatoid arthritis (RA) or spondyloarthritis (SpA) patients in a large practice-based research network of US rheumatologists to continue current immunomodulatory therapy or hold for 2 weeks after a booster dose of COVID-19 vaccine. LabCorp Cov2Quant IgG™ Spike assay was used to measure levels of anti-Receptor Binding Domain (RBD) IgG antibodies in response to vaccination and/or natural infection. Anti-nucleocapsid antibodies were measured to identify prior infection, which was also collected by patient self-report. Demographic characteristics were reported, and baseline COVID-19 RBD antibody levels examined in relation to time since and number of prior vaccine doses. Linear regression was used to evaluate determinants of mean log anti-RBD antibody titers and compared by drug categories.
Results: The 424 participants were 77% female, 91% white, 22% Hispanic with mean (SD) age of 58.3 (13.1) years and mean (SD) BMI of 32.1 (9.2) kg/m2. Most had RA (78%), with 36% TNFi use, 33% JAKi, 30% others (abatacept, IL-17i) at prior vaccine dose. Among the nucleocapsid negative, RBD antibody titers decreased with time since prior vaccine dose for all drug categories. After adjustment, time since prior vaccine dose was inversely association with RBD antibody titers (β=-0.13 [95%CI: -0.23,-0.03]), while increased number of prior vaccine doses showed a positive effect on mean titers (β=1.48 [0.97,2.00]). Compared to evidence of exposure to COVID-19 infection by Anti-nucleocapsid status, participant self-report of prior COVID had sensitivity of 54% (95% CI: 46%-62%) and specificity of 84% (79%-88%).
Conclusions: A decrease of anti-RBD IgG antibody levels in patients with RA or SpA taking immunomodulatory therapy was seen with increasing time following prior vaccine receipt. This effect was more pronounced in those with no evidence of prior COVID-19 infection. Self-report of prior COVID infection substantially misclassified nucleocapsid status and may confound immunogenicity outcomes in vaccine studies. Future analysis of the randomized trial results will look at the effect of holding or continuing immunomodulatory treatment at the time a SARS-CoV-2 booster is given.
