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

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.

Autoimmune and autoinflammatory conditions after COVID-19 vaccination. New case reports and updated literature review

“…However, greater reactogenicity may confer higher protection but could generate more adverse events. Remarkably, patients with ADs are not at increased risk of adverse events associated with vaccination [ 478 ], possibly due to the effect of immunomodulatory drugs on vaccine immunogenicity.…”

Novel insights into the management of rheumatoid arthritis: one year in review 2022

“…First, patients with RMDs should be strongly advised to receive a SARS-CoV-2 vaccination with any of the vaccines approved in their country. Despite a general fear and certain expectations, patient-reported AEs following SARS-CoV-2 vaccination were comparable to those reported in the general population, with rheumatic disease flares requiring medication changes occurring in less than 5% (29), and with no specific concerns regarding a third vaccination with respect to the second one (30). Second, patients with RMDs not using immunomodulatory or immunosuppressive treatment should receive SARS-CoV-2 vaccination preceding a treatment start with such therapy if clinically feasible, in particular before a course of B-cells depleting therapy.…”

Quantitative and qualitative features of acute phase-adverse events following SARS-CoV-2 vaccination in a large sample of people with multiple sclerosis

“…This is the first study directly comparing pwMS with age- and sex-matched HC, but the frequency of AP-AE in pwMS is similar to the one reported in previous studies and to the original RCT. ( Polack et al, 2020 , Briggs et al, 2022 , Lotan et al, 2021 , Wieske et al, 2022 ) The reason for a reduced incidence of AP-AEs in our cohort of controls might reside in ethnic, demographic or social differences from the general population of the original RCT.…”

“…Confirming previous findings on MS and other dysimmune diseases, females of both groups presented a significantly higher risk of developing AP-AE after at least one dose of vaccine. ( Briggs et al, 2022 , Wieske et al, 2022 ) This might be explained taking into account that females are more prone to mount a stronger immune response to infectious diseases, resulting in a faster clearance of pathogens, but also representing a risk factor for developing dysimmune diseases, ( Klein and Flanagan, 2016 ) as well as vaccines-related side effects. ( Klein and Flanagan, 2016 , Klein et al, 2010 , Cook, 2008 , Giefing-Kroll et al, 2015 )…”