Risk factors associated with short-term adverse events after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases
Authors: Wieske Luuk , Kummer Laura Y. L. , van Dam Koos P. J. , Stalman Eileen W. , van der Kooi Anneke J. , Raaphorst Joost , Löwenberg Mark , Takkenberg R. Bart , Volkers Adriaan G. , D’Haens Geert R. A. M. , Tas Sander W. , Spuls Phyllis I. , Bekkenk Marcel W. , Musters Annelie H. , Post Nicoline F. , Bosma Angela L. , Hilhorst Marc L. , Vegting Yosta , Bemelman Frederike J. , Killestein Joep , van Kempen Zoé L. E. , Voskuyl Alexandre E. , Broens Bo , Sanchez Agner Parra , Wolbink Gertjan , Boekel Laura , Rutgers Abraham , de Leeuw Karina , Horváth Barbara , Verschuuren Jan J. G. M. , Ruiter Annabel M. , van Ouwerkerk Lotte , van der Woude Diane , Allaart Cornelia F. , Teng Y. K. Onno , van Paassen Pieter , Busch Matthias H. , Jallah B. Papay , Brusse Esther , van Doorn Pieter A. , Baars Adája E. , Hijnen Dirkjan , Schreurs Corine R. G. , van der Pol W. Ludo , Goedee H. Stephan , Steenhuis Maurice , Rispens Theo , ten Brinke Anja , Verstegen Niels J. M. , Zwinderman Koos A. H. , van Ham S. Marieke , Kuijpers Taco W. , Eftimov Filip ,   on behalf of the T2B! immunity against SARS-CoV-2 study group
Published: March 2022

Abstract
Background
Studies have suggested incremental short-term adverse events (AE) after repeated vaccination. In this report, we assessed occurrence and risk factors for short-term AEs following repeated SARS-CoV-2 vaccination in patients with various immune-mediated inflammatory diseases (IMIDs).

Methods
Self-reported daily questionnaires on AEs during the first 7 days after vaccination were obtained of 2259 individuals (2081 patients and 178 controls) participating in an ongoing prospective multicenter cohort study on SARS-CoV-2 vaccination in patients with various IMIDs in the Netherlands (T2B-COVID). Relative risks were calculated for potential risk factors associated with clinically relevant AE (rAE), defined as AE lasting longer than 2 days or impacting daily life.

Results
In total, 5454 vaccinations were recorded (1737 first, 1992 second and 1478 third vaccinations). Multiple sclerosis, Crohn’s disease and rheumatoid arthritis were the largest disease groups. rAEs were reported by 57.3% (95% CI 54.8–59.8) of patients after the first vaccination, 61.5% (95% CI 59.2–63.7) after the second vaccination and 58% (95% CI 55.3–60.6) after the third vaccination. At day 7 after the first, second and third vaccination, respectively, 7.6% (95% CI 6.3–9.1), 7.4% (95% CI 6.2–8.7) and 6.8% (95% CI 5.4–8.3) of patients still reported AEs impacting daily life. Hospital admissions and allergic reactions were uncommon (<0.7%).
Female sex (aRR 1.43, 95% CI 1.32–1.56), age below 50 (aRR 1.14, 95% CI 1.06–1.23), a preceding SARS-CoV-2 infection (aRR 1.14, 95% CI 1.01–1.29) and having an IMID (aRR 1.16, 95% CI 1.01–1.34) were associated with increased risk of rAEs following a vaccination. Compared to the second vaccination, the first vaccination was associated with a lower risk of rAEs (aRR 0.92, 95% CI 0.84–0.99) while a third vaccination was not associated with increased risk on rAEs (aRR 0.93, 95% CI 0.84–1.02). BNT162b2 vaccines were associated with lower risk on rAEs compared to CX-024414 (aRR 0.86, 95% CI 0.80–0.93).

Conclusions
A third SARS-CoV-2 vaccination was not associated with increased risk of rAEs in IMID patients compared to the second vaccination. Patients with an IMID have a modestly increased risk of rAEs after vaccination when compared to controls. Most AEs are resolved within 7 days; hospital admissions and allergic reactions were uncommon.

Trial registration
NL74974.018.20, Trial ID: NL8900. Registered on 9 September 2020.