(A-357) Assessment of the Risk of 32 Adverse Effects of Special Interest following COVID-19 Vaccination in the Whole French Population

Background: Vaccines against COVID-19 have been administered to hundreds of millions of people worldwide. Numerous studies have assessed their safety, often investigating alerts released by health authorities. However, several signals suggested by published case reports remain unassessed.

Objectives: To assess the risk of 32 acute adverse events of special interest (AESI), prespecified by the European Medicines Agency, following COVID-19 vaccination in the French population.

Methods: Data from patients who experienced an acute AESI across auto-immune, cardiovascular, hematological, metabolic or neurological outcomes and who received ≥1 dose of COVID-19 vaccine in 2021 were extracted from the French National Healthcare Data System (SNDS) covering 67 million people. A 10% sample of the SNDS was used for AESI with a frequency (f) > 1.5/100 000. Self-controlled risk interval (SCRI) analyses were used to compare, for each AESI, the incidence rate during an interval defined as at-risk following vaccination and the incidence rate during a control interval. Risk and control intervals were unique for a patient, specific to each AESI, of equal length, and separated by a 30-day washout period. Analyses were conducted by vaccine brand and platform. Incidence rate ratios (IRR) were estimated using conditional Poisson regression models with a 95% confidence interval (95% CI).

Results: A total of 1 016 patients experienced ≥1 acute AESI (f ≤1.5/ 100 000) and received ≥1 dose of COVID-19 vaccine in 2021: mRNA [BNT162b2 = 77%; mRNA-1273 = 13%], adenoviral-vector [ChAdOx1 = 8%; Ad26.COV2.S = 2%]. Under the same conditions, 80 413 patients experienced ≥1 acute AESI (f >1.5/ 100 000) and were extracted from the 10% SNDS sample mRNA [BNT162b2 = 79%; mRNA-1273 = 16%], adenoviral-vector [ChAdOx1 = 4%; Ad26.COV2.S = 1%].
The SCRI highlights already acknowledged safety alerts such as Myocarditis with mRNA vaccines IRR=3.51 95% CI=[3.02; 4.08]. Some AESI showed 95% CI that excluded 1, echoing published case reports. For mRNA vaccines: Rhabdomylosis 1.34 [1.03; 1.74], Acute disseminated encephalomyelitis 10 [1.28; 78.12], Microangiopathy 1.41 [1.01; 1.97], Disseminated intravascular coagulation 2.08 [1.07; 4.03], Hemorrhagic stroke 1.43 [1.11; 1.84], Cerebral venous sinus thrombosis 1.87 [1.31; 2.67], which was also highlighted for ChAdOx1 3.75 [1.24; 11.30].

Conclusions: These analyses relying on a large population-based database strengthen safety signals associated with COVID-19 vaccines that remain to be investigated. Comparative cohort designs are ongoing to refine these signals and provide reliable risk quantification.