Risk factors associated with short-term adverse events after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases

Luuk Wieske, Laura Y L Kummer, Koos P J van Dam, Eileen W Stalman, Anneke J van der Kooi, Joost Raaphorst, Mark Löwenberg, R Bart Takkenberg, Adriaan G Volkers, Geert R A M D'Haens, Sander W Tas, Phyllis I Spuls, Marcel W Bekkenk, Annelie H Musters, Nicoline F Post, Angela L Bosma, Marc L Hilhorst, Yosta Vegting, Frederike J Bemelman, Joep KillesteinZoé L E van Kempen, Alexandre E Voskuyl, Bo Broens, Agner Parra Sanchez, Gertjan Wolbink, Laura Boekel, Abraham Rutgers, Karina de Leeuw, Barbara Horváth, Jan J G M Verschuuren, Annabel M Ruiter, Lotte van Ouwerkerk, Diane van der Woude, Cornelia F Allaart, Y K Onno Teng, Pieter van Paassen, Matthias H Busch, B Papay Jallah, Esther Brusse, Pieter A van Doorn, Adája E Baars, Dirkjan Hijnen, Corine R G Schreurs, W Ludo van der Pol, H Stephan Goedee, Maurice Steenhuis, Theo Rispens, Anja Ten Brinke, Niels J M Verstegen, Koos A H Zwinderman, T2B! immunity against SARS-CoV-2 study group, Filip Eftimov*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Web of Science)


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.

Original languageEnglish
Article number100
Number of pages6
JournalBMC Medicine
Issue number1
Publication statusPublished - 2 Mar 2022


  • BNT162 Vaccine
  • COVID-19/prevention & control
  • COVID-19 Vaccines/adverse effects
  • Cohort Studies
  • Female
  • Humans
  • Prospective Studies
  • Risk Factors
  • SARS-CoV-2
  • Vaccination/adverse effects

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