ABSTRACT
Background: COVID-19 vaccination strategies have evolved with increasing vaccine availability and emerging vaccine safety data. While data on immuno-genicity and safety of COVID vaccination strategies exists, there is limited data for people with immune mediated infammatory diseases (IMIDs) such as infam-matory arthritis (IA), systemic autoimmune rheumatic disease (SARD), infam-matory bowel disease (IBD) and multiple sclerosis (MS). Objectives: In IMID patients treated with homologous or heterogeneous COVID vaccines, to compare post vaccine IMID disease activity and COVID antibody responses. Methods: Between March 2021 and Dec 2021, patients with IA (n= 70;77% rheumatoid arthritis), SARD (n=82;70% lupus), IBD (n= 92;40% crohn's), and MS (n= 71;77% RRMS) self-reported COVID illness and exposure risks, and disease activity prior to and 1 month post both COVID-19 vaccinations (V1 and V2). Disease activity was assessed by the Systemic Lupus Activity Questionnaire (SLAQ) for SARDs, the RAPID-3 and RA fate index for IA, the IBD Symptoms Inventory-short form (IBDSI) and IBD fare index for IBD and the 25 meter walk and 9 hole peg test and Expanded Disability Status Scale (EDSS) for MS. Patient reported fare state was assessed using the relevant questions these indices (SLAQ 'Have you had a fare?';RA Flare index 'Are you in a fare?';IBD fare 'My IBD is sometimes to continously active'). Disease activity and serum anti-spike, anti-receptor binding domain (RBD) and anti-nucleocapsid (NC) IgG antibody titers at 30 days post V2 were compared across vaccine courses and to age-sex matched vaccinated blood donor controls (CNTS). Results: Patients were predominantly female (79.7%), with a mean (standard deviation-sd) age of 56 (15) years;8% had suspected or diagnosed COVID-19 illness;1.2% positive anti-NC (Table 1). For all IMIDS, the majority received mRNA vaccines-BNT162b2 (BNT) or mRNA1273 (V1 74%;V2 97%;) the rest received ChAdOx1 viral vector vaccines;71% received homologogous vaccines (ChAdOx1-ChAdOx n=6;BNT-BNT n=174;mRNA1271-mRNA1273 n=21;ChAdOx1-BNT n=36;ChAdOx1-mRNA1273 n=30;BNT-mRNA1273 n=15;mRNA1273-BNT n=3;other n=4). For most IMIDs, disease activity was similar before and after each vaccination. Post V2 disease activity did not differ between homologous versus heterologous vaccines nor by vaccine type (RAPID3;SLAQ, 25 meter walk and 9 hole peg test and EDSS overall and subscales, IBDSI overall and subscales all p=NS). In 254 IMIDs, most seroconverted (anti-spike 86%;anti-RBD 96%). Seroconversion rates for CNTS were 98.1% for anti-Spike and 3.5% for anti-NC. Antibody titers were higher following homologous mRNA (BNT or mRNA12723) than homologous vector vaccine (Figure 1). For IMIDs primed with ChAdOx vector vaccine, boosting with BNT or mRNA1273 generated similarly increased anti-Spike and anti-RBD titers. Conclusion: Heterologous COVID vaccination improves seroconversion rates following a viral vector vaccine and does not lead to disease fare in most IMID patients. While data is needed to assess vaccine effectiveness, duration of immu-nogenicity and effects of subsequent vaccination, this work supports mixing COVID vaccines for IMID patients.
ABSTRACT
Background: Neurological disability progression occurs across the spectrum of people living with multiple sclerosis (PwMS). Currently, no treatments exist that substantially modify the course of clinical progression in MS, one of the greatest unmet needs in clinical practice. Characterizing the determinants of clinical progression is essential for the development of novel therapeutic agents and treatment approaches that target progression in PwMS. Objectives: The overarching aim of CanProCo is to evaluate a wide spectrum of factors associated with the onset and rate of disease progression in MS, and to describe how these factors interact with one another to influence progression. Methods: CanProCo is a prospective, observational cohort study aiming to recruit 1000 individuals with radiologically-isolated syndrome (RIS), relapsing-remitting MS (RRMS), and primary-progressive MS (PPMS) within 10-15 years of disease onset, and 50 healthy controls (HCs) from five large academic MS centers in Canada. Participants undergo detailed clinical evaluations annually. A subset of participants enrolled within 5-10 years of disease onset (n=500) also have blood, cerebrospinal fluid, and MRIs collected facilitating study of biological measures (e.g. single-cell RNAsequencing[ scRNASeq]), MRI-based microstructural assessment, participant characteristics (self-reported, performance-based, clinician- assessed, health-system based), and environmental factors as determinants contributing to the differential progression in MS. Results: Recruitment commenced in April/May 2019 and n=536 patients have been recruited to date (RRMS=457, PPMS=35, RIS=25, HC=19). Baseline age, sex distribution, and Expanded Disability Status Scale (EDSS) scores (median, range) of each subgroup are: RRMS=38 years, 73% female, EDSS=1.5 (0-6.0);PPMS=52 years, 40% female, EDSS=4.0 (1.5-6.5);RIS=41 years, 68% female, EDSS=0 (0-3.0);HC=37 years, 63% female. Recruitment has surpassed the 50% target but has been paused due to the COVID-19 pandemic. scRNASeq on frozen blood samples has been validated. Conclusions: Halting the progression of MS is a fundamental clinical need to improve the lives of PwMS. Achieving this requires leveraging transdisciplinary approaches to better characterize mechanisms underlying clinical progression. CanProCo is the first prospective cohort study aiming to characterize these determinants to inform the development and implementation of efficacious and effective interventions.