Article Text
Abstract
Background The impact of immunosuppressants on COVID-19 vaccination response and durability in patients with immune-mediated inflammatory diseases (IMID) is yet to be fully characterized. Humoral response may be attenuated in these patients especially those on B cell depleting therapy and higher doses of corticosteroids, but data regarding other immunosuppressants are scarce.
Objectives We aimed to investigate antibody and T cell responses and durability to SARS-CoV-2 mRNA vaccines (BNT162b and/or mRNA 1273) in IMID patients on immunomodulatory maintenance therapy other than B-cell depleting therapy and corticosteroids.
Methods This prospective observational cohort study examined the immunogenicity of SARS-CoV-2 mRNA vaccines in adult patients with IMIDs (psoriatic arthritis, psoriasis, inflammatory bowel disease and rheumatoid arthritis) with or without maintenance immunosuppressive therapies (anti-TNF, methotrexate/azathioprine [MTX/AZA], anti-TNF + MTX/AZA, anti IL12/23, anti-IL-17, anti-IL23) compared to healthy controls. Automated ELISA for IgGs to spike trimer, spike receptor binding domain (RBD) and the nucleocapsid (NP) and T-cell release of 9 cytokines (IFNg, IL2, IL4, IL17A, TNF) and cytotoxic molecules (sFasL, GzmA, GzmB, Perforinin) in cell culture supernatants following stimulation with spike or NP peptide arrays were conducted at 4 time points: T1=pre vaccination, T2=median 26 days after dose 1, T3=median 16 days after dose 2 and T4=median 106 days after dose 2. Neutralization assays against four SARS-CoV-2 variants (wild type, delta, beta and gamma) were conducted at T3.
Results We followed 150 subjects: 26 healthy controls and 124 IMID patients: 9 untreated, 44 on anti-TNF, 16 on anti-TNF with MTX/AZA, 10 on anti-IL23, 28 on anti-IL12/23, 9 on anti-IL17, 8 on MTX/AZA (Table 1). Most patients mounted antibody and T cell responses with increases from dose 1 to dose 2 (100% seroconversion at T3) and some decline by T4, with variability within groups. Antibody levels and neutralization efficacy was lower in anti-TNFgroups (anti-TNF, anti-TNF + MTX/AZA) compared to controls and waned by T4 (Figure 1). T cell responses were not consistently different between groups. Pooled data showed a higher antibody response to mRNA-1273 compared to BNT162b.
Conclusion Following 2 doses of mRNA vaccination there is 100% seroconversion in IMID patients on maintenance therapy. Antibody levels and neutralization efficacy in anti-TNF group are lower than controls, and wane substantially by 3 months after dose 2. These findings highlight the need for third dose in patients undergoing treatment with anti-TNF therapy and continued monitoring of immunity in these patient groups, taking into consideration newer variants and additional vaccine doses.
Acknowledgements This work was funded by a donation from Juan and Stefania Speck and by grants VR-1 172711, VS1-175545, FDN-143250, GA1- 177703 and GA2- 177716, from Canadian Institutes of Health Research and COVID Immunity task force and by Sinai Health Foundation
Disclosure of Interests Naomi Finkelstein: None declared, Roya M. Dayam: None declared, Jaclyn Law: None declared, Rogier Goetgebuer: None declared, Gary Chao: None declared, Kento T. Abe: None declared, Mitchell Sutton: None declared, Joanne M. Stempak: None declared, Daniel Pereira: None declared, David Croitoru: None declared, Lily Acheampong: None declared, Saima Rizwan: None declared, Klaudia Rymaszewski: None declared, Raquel Milgrom: None declared, Darshini Ganatra: None declared, Nathalia V. Batista: None declared, Melanie Girard: None declared, Irene Lau: None declared, Ryan Law: None declared, Michelle Cheung: None declared, Bhavisha Rathod: None declared, Julia Kitaygorodsky: None declared, Reuben Samson: None declared, Queenie Hu: None declared, Nigil Haroon: None declared, Robert Inman Consultant of: AbbVie, Janssen, Lilly, Novartis., Grant/research support from: AbbVie, Novartis, Vincent Piguet Consultant of: AbbVie, Almirall, Celgene, Janssen, Kyowa Kirin Co. Ltd, LEO Pharma,
Novartis, Pfizer, Sanofi, UCB, and Union Therapeutic, Grant/research support from: Unrestricted educational grants from AbbVie, Bausch Health, Celgene, Janssen, LEO Pharma, Lilly, L’Oréal, NAOS, Novartis, Pfizer, Pierre-Fabre, Sandoz, and Sanofi, Mark Silverberg Speakers bureau: AbbVie, Janssen, Takeda, Pfizer, Gilead and Amgen, Consultant of: AbbVie, Janssen, Takeda, Pfizer, Gilead and Amgen, Grant/research support from: AbbVie, Janssen, Takeda, Pfizer, Gilead and Amgen, Anne-Claude Grigras: None declared, Tania H. Watts: None declared, Vinod Chandran Consultant of: AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Eli-Lilly.