IMMUNE RESPONSE AFTER COVID-19 VACCINATION DURING MAINTANACE THERAPY IN IMMUNE-MEDIATED INFLAMMATORY DISEASES: AN OBSERVATIONAL COHORT STUDY

ABSTRACT

BACKGROUND Little is known about the impact of immunosuppressants on COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMID). Although humoral response may be attenuated in patients using immunomodulators (IMM) and TNFinhibitors (anti-TNF), data regarding cellular response are scarce and conflicting. This study was aimed to identify immune response to COVID-19 vaccination in IMID patients. METHODS A prospective observational multicentre cohort study was conducted to examine the immunogenicity of mRNA vaccines to SARS-CoV-2 in adult IMID patients using immunosuppressive therapy (anti-TNF, IMM, anti-TNF+IMM, anti-IL12/23, anti-IL-17, anti-IL-23) or no therapy as compared to healthy controls (HC). Patient details and vaccination history were recorded. Blood samples were drawn at 3 time points before, 3-4 weeks after first and 2 weeks after second vaccination. Humoral immune response to S and RBD proteins were assessed by ELISA. Neutralization was tested against 4 variants of SARS-CoV-2 by surrogate neutralization ELISA. Cellular immune responses were determined based on analysis of 9 secreted cytokines and cytotoxic molecules after stimulation of PBMC with S peptide pools. Response to N protein was used to assess SARS-CoV-2 exposure. RESULTS A total of 159 subjects (133 IMID patients and 26 HC) were included in this study (median age 42 years [IQR 30-53], 52% male). Of 133 IMID patients, 87 had inflammatory bowel disease, 23 psoriatic arthritis, 18 psoriasis, 11 ankylosing spondylarthritis and 4 rheumatoid arthritis. Of these, 44 used anti-TNF, 9 IMM, 18 anti-TNF+IMM, 33 anti-IL-12/23, 9 anti-IL-17, 10 anti-IL-23 therapy and 10 no therapy. All subjects received 2 doses of mRNA vaccines (2x Pfizer, 2x Moderna or mixed) between December 2020 and September 2021. The vast majority of subjects had minimal binding antibody and T cell responses to N, indicating they were COVID-19 naïve. After dose 1, anti-TNF group had lower IL-2 vs untreated IMID (p<0.01), and the anti-IL-23 group had lower IFN-g vs HC (p<0.01), though there was wide variation in responses within groups. Following dose 2, median responses between groups were mostly similar, but antibody responses were significantly lower in patients on anti-TNF as compared to HC in subjects that received two doses of Pfizer (p=0.01). Pooled data for all subjects combined show a higher response to Moderna over Pfizer in ELISA, neutralization and T cell readouts, and a lower response for those over 60 years of age after dose 2. Longer follow-up is in process to monitor the durability of these responses over time and after third dose. CONCLUSION Immune responses after 2 doses of mRNA vaccines in immunocompromised IMID patients largely reach the level of that of HC albeit antibody responses in the anti-TNF group are weaker and with wide variability between subjects within some groups