Analysis of adverse events following COVID-19 vaccination and infection: A retrospective, comparative cohort study using a claims database from Discovery Health, a managed care organisation in South Africa
DOI:
https://doi.org/10.7196/SAMJ.2026.v116i5.3941Keywords:
COVID-19, Adverse events, COVID-19 vaccinesAbstract
Background. Adverse events following COVID-19 vaccination have been studied extensively in recent years. However, there remains a paucity of data directly comparing adverse events among COVID-19 vaccinees and individuals with SARS-CoV-2 infection within the insured population in South Africa (SA). Moreover, the breadth of conditions assessed in this study exceeds that of most existing research, providing a unique perspective on potential immune-mediated outcomes. This study therefore contributes to a more comprehensive understanding of the risk-benefit profile of COVID-19 vaccination across different age groups.
Objective. To evaluate the rate of adverse events occurring in COVID-19 vaccinees compared with individuals who have had SARS-CoV-2 infection.
Methods. We conducted a retrospective cohort study, matching vaccinated individuals and those who have had a SARS-CoV-2 infection with comparable unexposed counterparts. Incident risk rates for 99 possible immune-mediated adverse events were compared between populations over a 42-day observation period to estimate relative risk ratios and confidence intervals. We used data from Discovery Health, a large managed care organisation in SA.
Results. A total of 3 112 918 individuals aged ≥12 years who received a COVID-19 vaccination were included in the study, with an average of 76% successfully matched to a suitable comparator based on their risk profile. Additionally, 443 220 individuals with documented SARS-CoV-2 infection were analysed, with an average of 99.7% matched to an appropriate comparator. For recipients of the BNT162b2 vaccine, aged 12 - 17 years, we found an increased risk of lymphadenopathy and vertigo, compared with an increased risk of appendicitis, arrhythmia, encephalomyelitis, lymphadenopathy, myocarditis, seizure, syncope, type 1 diabetes and vertigo post SARS-CoV-2 infection. For those aged ≥18 years, we found no increased risk for any conditions post BNT162b2 vaccination. Additionally, no conditions post AD26.COV2.S vaccination had an increased risk for any age group. Post documented SARS-CoV-2 infection for persons in age groups 18 - 39, 40 - 59 and ≥60 years, we found an increased risk of acute kidney injury, anaemia, appendicitis, arrhythmia, axonal and neuronal neuropathy, cerebrovascular accident, deep-vein thrombosis, encephalomyelitis, endometriosis, eosinophilic oesophagitis, fibrosing alveolitis, glomerulonephritis, inflammatory bowel disease, intracranial haemorrhage, lymphadenopathy, myocardial infarction, myocarditis, myositis, pericarditis, pulmonary embolism, rheumatic fever, seizure, syncope, thrombocytopenia, type 1 diabetes, urticaria, vertigo, multiple sclerosis, cholangitis and/or pancreatitis. Notably, not all conditions presented with an increased risk in each age group.
Conclusions. Across all age subgroups analysed, the risks associated with SARS-CoV-2 infection exceeded the increased risks following COVID-19 vaccination.
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