(346) Measuring Association of Acute Disseminated Encephalomyelitis and Transverse Myelitis following COVID-19 vaccination using a Self-Controlled Case Series Analysis of Real-World Linked Data

Background: Acute Disseminated Encephalomyelitis (ADEM) and Transverse Myelitis (TM) are immune mediated acquired demyelinating syndromes. Both have been described in temporal association following various vaccinations in case reports, case series and other observational studies. A recent study conducted by The Global Vaccine Data Network (GVDN) observed an excess of ADEM and TM cases following the adenoviral vectored ChAdOx1 nCoV-19 and mRNA-1273 vaccines, compared with historically expected background rates from prior to the pandemic. Further causal association studies were recommended to explore these potential associations.

Objectives: To determine if there is increased risk of ADEM or TM associated with COVID-19 vaccination

Methods: We utilized an Australian vaccine datalink, Vaccine Safety Health Link (VSHL) containing vaccination records sourced from the Australian Immunisation Register, and hospital admission records from the Victorian Admitted Episodes Dataset for 6.7 million people, to perform a self-controlled case series analysis in R (version 4.2.3). Our study cohort comprised persons with a G040 (ADEM) or G373 ICD-10-AM coded admission during January 2021 to October 2023, with new onset incidence assumed using a 365-day washout period. We calculated the relative incidence (RI) for ADEM and TM in a biological plausible 1–42-day risk window following COVID-19 vaccination compared with control periods, stratified by vaccinee sex, age category of ≤50 or >50 years, vaccine and dose received, with 95% confidence intervals (CI) and p-values.

Results: Following 18,133,383 COVID-19 vaccine doses administered, 37 ADEM and 155 TM eligible admitted cases were identified. We detected an association between adenovirus vector COVID-19 vaccinations and ADEM (RI: 3.74 [95 %CI 1.02,13.70]), with a non-statistically significant dose effect risk following dose 1 (RI: 4.50 [95 %CI: 0.98,20.61]) and also with TM (RI: 2.49 [95 %CI: 1.07,5.79]), with no increased risk of TM found following dose 2 (RI: 0.46 [95 %CI: 0.06,3.37]). No significant difference was detected in incidence by sex or 50-year age category and no association was identified between mRNA COVID-19 vaccines and ADEM or TM.

Conclusions: These findings translate to an extremely rare absolute risk of ADEM (0.78 per million doses) and TM (1.82 per million doses) following vaccination, thus vaccination decisions should be weighed against the well-established protective benefits from COVID-19 disease. This study demonstrates the value of collaborative networks leveraging large population sizes to examine important vaccine safety questions regarding rare adverse events, as well as the value of linked population level datasets, such as VSHL, to rapidly explore potential associations identified.