BACKGROUND: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. METHODS: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. FINDINGS: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. INTERPRETATION: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. FUNDING: None.

1st Department Anaesthesiology and Intensive Therapy Professor Critical Care Research Medical University Lublin Lublin Poland

Bakar Computational Health Sciences Institute University of California San Francisco San Francisco CA USA

British Heart Foundation Data Science Centre London UK

Center for Data driven Insights and Innovation University of California Health Oakland CA USA

Centre for Statistics in Medicine NDORMS University of Oxford Oxford UK

Clinerion Basel Switzerland

Clinical Practice Research Datalink Medicines and Healthcare Products Regulatory Agency London UK

College of Pharmacy Prince Sattam Bin Abdulaziz University Alkharj Kingdom of Saudi Arabia

Department of Biomedical Informatics Columbia University Irving Medical Center New York NY USA

Department of Biostatistics University of California Los Angeles Los Angeles CA USA

Department of Informatics Imaging and Data Sciences University of Manchester Manchester UK

Department of Medical Informatics Erasmus University Medical Center Rotterdam the Netherlands

Department of Medical Information Assistance Publique Hopitaux de Marseille Marseille France

Department of Medicine and Life Sciences Universitat Pompeu Fabra Barcelona Spain

Department of Public Health University of Southern Denmark Odense Denmark

Department of Systems Engineering School of Engineering Universidad del Norte Barranquilla Colombia

Division of Clinical Pharmacology Department of Medical Pharmacology Istanbul Faculty of Medicine Istanbul University Istanbul Türkiye

Division of Population Health and Genomics University of Dundee Dundee UK

Easter Eggs Paris France

Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol 1 Gurina Barcelona Spain

Fundación para la Investigación e Innovación Biosanitaria en Atención Primaria Madrid Spain

Health Data Research UK London UK

Health Informatics Centre University of Dundee Dundee UK

Heliant Belgrade Serbia

Hospital del Mar Department of Innovation and Digital Transformation Barcelona Spain

Hospital del Mar Medical Research Institute Barcelona Spain

Hospital Universitario 12 de Octubre Madrid Spain

Instituto de Investigación Hospital 12 de Octubre Madrid Spain

IQVIA Falls Church VA USA

Janssen Pharmaceutical Research and Development LLC Titusville NJ USA

Medaman BV Geel Flanders Belgium

New York Presbyterian Hospital New York NY USA

O'Brien Institute for Public Health Faculty of Medicine University of Calgary Alberta CA USA

Odysseus Data Services Prague Czechia

OHDSI Collaborators Observational Health Data Sciences and Informatics New York NY USA

School of Public Health and Community Medicine Institute of Medicine Sahlgrenska Academy University of Gothenburg Gothenburg Sweden

Stanford School of Medicine Stanford University Palo Alto CA USA

University College London Institute of Health Informatics London UK

University of Colorado Anschutz Medical Campus Denver CO USA

University of Tartu Tartu Estonia

VA Informatics and Computing Infrastructure US Department of Veterans Affairs Salt Lake City UT USA

VeraTech for Health Valencia Spain

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