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Multicenter Study
. 2022 Mar 2;20(1):100.
doi: 10.1186/s12916-022-02310-7.

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

Luuk Wieske #  1   2 , Laura Y L Kummer #  1   3 , Koos P J van Dam  1 , Eileen W Stalman  1 , Anneke J van der Kooi  1 , Joost Raaphorst  1 , Mark Löwenberg  4 , R Bart Takkenberg  4 , Adriaan G Volkers  4 , Geert R A M D'Haens  4 , Sander W Tas  5 , Phyllis I Spuls  6   7 , Marcel W Bekkenk  6 , Annelie H Musters  6 , Nicoline F Post  6 , Angela L Bosma  6 , Marc L Hilhorst  8 , Yosta Vegting  8 , Frederike J Bemelman  8 , Joep Killestein  9 , Zoé L E van Kempen  9 , Alexandre E Voskuyl  10 , Bo Broens  10 , Agner Parra Sanchez  5   10 , Gertjan Wolbink  11 , Laura Boekel  11 , Abraham Rutgers  12 , Karina de Leeuw  12 , Barbara Horváth  13 , Jan J G M Verschuuren  14 , Annabel M Ruiter  14 , Lotte van Ouwerkerk  15 , Diane van der Woude  15 , Cornelia F Allaart  15 , Y K Onno Teng  16 , Pieter van Paassen  17 , Matthias H Busch  17 , B Papay Jallah  17 , Esther Brusse  18 , Pieter A van Doorn  18 , Adája E Baars  18 , Dirkjan Hijnen  19 , Corine R G Schreurs  19 , W Ludo van der Pol  20 , H Stephan Goedee  20 , Maurice Steenhuis  3 , Theo Rispens  3 , Anja Ten Brinke  3 , Niels J M Verstegen  3 , Koos A H Zwinderman  21 , S Marieke van Ham #  3   22 , Taco W Kuijpers #  23 , Filip Eftimov #  24 ; T2B! immunity against SARS-CoV-2 study group
Affiliations
Multicenter Study

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

Luuk Wieske et al. BMC Med. .

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.

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Conflict of interest statement

JV reported financial support from Target to B consortium, Prinses Beatrix Spierfonds, and has been involved in trials or consultancies for Argenx, Alexion, Rapharma. BH reported fees from Roche, Sanofi, Novartis and Janssen. JK reported speaking and consulting relationships with Biogen, Genzyme, Merck, Novartis, Roche, Sanofi and TEVA. AmsterdamUMC, location VUmc, MS Center Amsterdam, has received financial support for research activities from Biogen, Celgene, Genzyme, Merck, Novartis, Roche, Sanofi and TEVA. PS reported being involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of e.g. psoriasis and atopic dermatitis, for which financial compensation is paid to the department/hospital and is one of the main investigator of the TREAT registry taskforce and SECURE-AD registry. ML reported to have served as speaker and/or is a principal investigator for Abbvie, Alimentiv, Bristol Myers Squibb, Celgene, Covidien, Dr. Falk, Ferring Pharmaceuticals, Galapagos, Gilead, GlaxoSmithKline, Janssen-Cilag, Merck Sharp & Dohme, Pfizer, Protagonist Therapeutics, Receptos, Takeda, Tillotts and Tramedico. FE, GW and TK reported a grant from ZonMW for COVID research in patients with auto-immune diseases. No other disclosures were reported.

Figures

Fig. 1
Fig. 1
Relative risks for adverse events after SARS-CoV-2 vaccination. Figure showing the adjusted relative risk, including 95% confidence interval, for relevant systemic adverse events after first and third vaccination versus second vaccination, IMID versus no IMID, BNT162b2 and ChAdOx1 nCoV-19 vaccine versus CX-024414, IMID patients versus healthy controls, preceding SARS-CoV-2 infection before first vaccination versus no preceding SARS-CoV-2 infection, age below 50 years versus age above 50 and female versus male sex
See this image and copyright information in PMC

References

    1. Mrak D, Tobudic S, Koblischke M, et al. SARS-CoV-2 vaccination in rituximab-treated patients: B cells promote humoral immune responses in the presence of T-cell-mediated immunity. Ann Rheum Dis. 2021. 10.1136/annrheumdis-2021-220781 Epub ahead of print. - PubMed
    1. Achiron A, Mandel M, Dreyer-Alster S, et al. Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies. Ther Adv Neurol Disord. 2021;14:17562864211012835. - PMC - PubMed
    1. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383(27):2603–2615. doi: 10.1056/NEJMoa2034577. - DOI - PMC - PubMed
    1. Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403–416. doi: 10.1056/NEJMoa2035389. - DOI - PMC - PubMed
    1. Ebinger JE, Fert-Bober J, Printsev I, et al. Antibody responses to the BNT162b2 mRNA vaccine in individuals previously infected with SARS-CoV-2. Nat Med. 2021;27(6):981–984. doi: 10.1038/s41591-021-01325-6. - DOI - PMC - PubMed

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