{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:27:15Z","timestamp":1791412035470,"version":"4.3.3"},"posted":{"date-parts":[[2021,3,26]]},"group-title":"Epidemiology","reference-count":28,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,4,17]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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\u2019s 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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Findings<\/jats:title>\n                  <jats:p>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 \u226585 years.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2021.03.25.21254315","type":"posted-content","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T16:20:17Z","timestamp":1616775617000},"source":"Crossref","is-referenced-by-count":35,"title":["Characterizing the incidence of adverse events of special interest for COVID-19 vaccines across eight countries: a multinational network cohort study"],"prefix":"10.64898","author":[{"given":"Xintong","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Ostropolets","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupa","family":"Makadia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azza","family":"Shaoibi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gowtham","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8630-5347","authenticated-orcid":false,"given":"Anthony G.","family":"Sena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia","family":"Martinez-Hernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Delmestri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Verhamme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R","family":"Rijnbeek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8274-0357","authenticated-orcid":false,"given":"Talita","family":"Duarte-Salles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9818-479X","authenticated-orcid":false,"given":"Marc","family":"Suchard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Hripcsak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3950-6346","authenticated-orcid":false,"given":"Daniel","family":"Prieto-Alhambra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2021041907400560000_2021.03.25.21254315v3.1","doi-asserted-by":"publisher","DOI":"10.46945\/bpj.10.1.03.01"},{"key":"2021041907400560000_2021.03.25.21254315v3.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61877-8"},{"key":"2021041907400560000_2021.03.25.21254315v3.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2012.12.015"},{"key":"2021041907400560000_2021.03.25.21254315v3.4","unstructured":"Center for Biologics Evaluation and Research Office of Biostatistics and Epidemiology. CBER Surveillance Program Background Rates of Adverse Events of Special Interest for COVID-19 Vaccine Safety Monitoring Protocol. https:\/\/www.bestinitiative.org\/wp-content\/uploads\/2021\/02\/C19-Vaccine-Safety-AESI-Background-Rate-Protocol-FINAL-2020.pdf (accessed March 11, 2021)."},{"key":"2021041907400560000_2021.03.25.21254315v3.5","unstructured":"Willame C , Dodd C , Gini R , et al. Background rates of Adverse Events of Special Interest for monitoring COVID19 vaccines, an ACCESS study. Source: http:\/\/www.encepp.eu\/phact_links.shtml"},{"key":"2021041907400560000_2021.03.25.21254315v3.6","unstructured":"Report of CIOMS Working Group on Vaccine Safety. CIOMS Guide to Active Vaccine Safety Surveillance. https:\/\/cioms.ch\/wp-content\/uploads\/2020\/04\/240WEB-CIOMS-Guide-AVSS-20170202-protected.pdf (accessed March 11, 2021)."},{"key":"2021041907400560000_2021.03.25.21254315v3.7","first-page":"553","article-title":"Feasibility and utility of applications of the common data model to multiple, disparate observational health databases","volume":"22","year":"1093","journal-title":"J Am Med Inf Assoc"},{"key":"2021041907400560000_2021.03.25.21254315v3.8","first-page":"574","article-title":"Observational Health Data Sciences and Informatics (OHDSI): Opportunities for observational researchers","volume":"216","year":"2015","journal-title":"Stud Health Technol Inform"},{"key":"2021041907400560000_2021.03.25.21254315v3.9","unstructured":"bc-coordinator. Priority list of adverse events of special interest: COVID-19. 2020; published online June 10. https:\/\/brightoncollaboration.us\/priority-list-aesi-covid\/ (accessed March 11, 2021)."},{"key":"2021041907400560000_2021.03.25.21254315v3.10","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(86)90046-2"},{"key":"2021041907400560000_2021.03.25.21254315v3.11","doi-asserted-by":"publisher","DOI":"10.1136\/ebmental-2019-300117"},{"key":"2021041907400560000_2021.03.25.21254315v3.12","unstructured":"The Council for International Organizations of Medical Sciences (CIOMS). Guidelines for Preparing Core Clinical-Safety Information on Drugs Second Edition \u2013 Report of CIOMS Working Groups III and V. Geneva, 1999."},{"key":"2021041907400560000_2021.03.25.21254315v3.13","unstructured":"R Core Team (2020). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https:\/\/www.R-project.org\/."},{"key":"2021041907400560000_2021.03.25.21254315v3.14","doi-asserted-by":"crossref","unstructured":"Wise J. Covid-19: European countries suspend use of Oxford-AstraZeneca vaccine after reports of blood clots. BMJ 2021; 372: 699.","DOI":"10.1136\/bmj.n699"},{"key":"2021041907400560000_2021.03.25.21254315v3.15","unstructured":"Coronavirus vaccine - weekly summary of Yellow Card reporting. https:\/\/www.gov.uk\/government\/publications\/coronavirus-covid-19-vaccine-adverse-reactions\/coronavirus-vaccine-summary-of-yellow-card-reporting (accessed March 22, 2021)."},{"key":"2021041907400560000_2021.03.25.21254315v3.16","unstructured":"CoViD Vaccines and thrombotic events: Possibility of mRNA translation and spike protein synthesis by platelets? 2021; published online March 15. https:\/\/www.bmj.com\/content\/372\/bmj.n699\/rr-6 (accessed March 22, 2021)."},{"key":"2021041907400560000_2021.03.25.21254315v3.17","unstructured":"COVID-19 Vaccine AstraZeneca: benefits still outweigh the risks despite possible link to rare blood clots with low blood platelets. 2021; published online March 18. https:\/\/www.ema.europa.eu\/en\/news\/covid-19-vaccine-astrazeneca-benefits-still-outweigh-risks-despite-possible-link-rare-blood-clots (accessed March 22, 2021)."},{"key":"2021041907400560000_2021.03.25.21254315v3.18","doi-asserted-by":"publisher","DOI":"10.3928\/0090-4481-20040901-11"},{"key":"2021041907400560000_2021.03.25.21254315v3.19","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61877-8"},{"key":"2021041907400560000_2021.03.25.21254315v3.20","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e5823"},{"key":"2021041907400560000_2021.03.25.21254315v3.21","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s40264-020-01031-1","article-title":"Incidence rates of autoimmune diseases in European healthcare databases: A contribution of the ADVANCE project","volume":"44","year":"2021","journal-title":"Drug Saf"},{"issue":"Suppl 10","key":"2021041907400560000_2021.03.25.21254315v3.22","first-page":"K98","article-title":"Post-licensure rapid immunization safety monitoring program (PRISM) data characterization","volume":"31","year":"2013","journal-title":"Vaccine"},{"key":"2021041907400560000_2021.03.25.21254315v3.23","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1159\/000369344","article-title":"Estimation of background incidence rates of Guillain-Barr\u00e9 syndrome in Germany - a retrospective cohort study with electronic healthcare data","volume":"43","year":"2014","journal-title":"Neuroepidemiology"},{"key":"2021041907400560000_2021.03.25.21254315v3.24","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s10072-018-3688-4","article-title":"Incidence study of Guillain-Barr\u00e9 syndrome in the province of Ferrara, Northern Italy, between 2003 and 2017. A 40-year follow-up","volume":"40","year":"2019","journal-title":"Neurol Sci"},{"key":"2021041907400560000_2021.03.25.21254315v3.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.10.115"},{"key":"2021041907400560000_2021.03.25.21254315v3.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2021.03.016"},{"key":"2021041907400560000_2021.03.25.21254315v3.27","doi-asserted-by":"crossref","first-page":"275","DOI":"10.2147\/CLEP.S199839","article-title":"Guillain-Barr\u00e9 syndrome in Denmark: validation of diagnostic codes and a population-based nationwide study of the incidence in a 30-year period","volume":"11","year":"2019","journal-title":"Clin Epidemiol"},{"key":"2021041907400560000_2021.03.25.21254315v3.28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2011.00356.x"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2021.03.25.21254315","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T14:11:47Z","timestamp":1768486307000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2021.03.25.21254315"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,26]]},"references-count":28,"URL":"https:\/\/doi.org\/10.1101\/2021.03.25.21254315","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1136\/bmj.n1435","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2021,3,26]]},"subtype":"preprint"}}