Characterizing the incidence of adverse events of special interest for COVID-19 vaccines across eight countries: a multinational network cohort study.

BACKGROUND

As large-scale immunization programs against COVID-19 proceed around the world, safety signals will emerge that need rapid evaluation. We report population-based, age- and sex-specific background incidence rates of potential adverse events of special interest (AESI) in eight countries using thirteen databases.

METHODS

This multi-national network cohort study included eight electronic medical record and five administrative claims databases from Australia, France, Germany, Japan, Netherlands, Spain, the United Kingdom, and the United States, mapped to a common data model. People observed for at least 365 days before 1 January 2017, 2018, or 2019 were included. We based study outcomes on lists published by regulators: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain-Barre syndrome, hemorrhagic and non-hemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, and transverse myelitis. We calculated incidence rates stratified by age, sex, and database. We pooled rates across databases using random effects meta-analyses. We classified meta-analytic estimates into Council of International Organizations of Medical Sciences categories: very common, common, uncommon, rare, or very rare.

FINDINGS

We analysed 126,661,070 people. Rates varied greatly between databases and by age and sex. Some AESI (e.g., myocardial infarction, Guillain-Barre syndrome) increased with age, while others (e.g., anaphylaxis, appendicitis) were more common in young people. As a result, AESI were classified differently according to age. For example, myocardial infarction was very rare in children, rare in women aged 35-54 years, uncommon in men and women aged 55-84 years, and common in those aged ≥85 years.

INTERPRETATION

We report robust baseline rates of prioritised AESI across 13 databases. Age, sex, and variation between databases should be considered if background AESI rates are compared to event rates observed with COVID-19 vaccines.

Déclaration de conflit d'intérêts

Declaration of interests DPA’s research group has received research grants from the European Medicines Agency, from the Innovative Medicines Initiative, from Amgen, Chiesi, and from UCB Biopharma; and consultancy or speaker fees from Astellas, Amgen and UCB Biopharma. GH and AO receive funding from the US National Institutes of Health and the US Food and Drug Administration. KV and PR work for a research group who receives/received unconditional research grants from Yamanouchi, Pfizer-Boehringer Ingelheim, Novartis, GSK, Amgen, Chiesi none of which relates to the content of this paper. PBR, RM, AS, GR, AGS are employee of Janssen Research and Development, and shareholder in Johnson & Johnson. MAS receives grants and contracts from the US Food & Drug Administration and the US Department of Veterans Affairs within the scope of this research, and grants and contracts from the US National Institutes of Health, IQVIA and Private Health Management outside the scope of this research. Funders had no role in the conceptualization, design, data collection, analysis, decision to publish nor preparation of the manuscript. TDS has no conflicts of interest to declare. EM has no conflicts of interest to declare.