A large South African study, involving more than 3m people from the Discovery Health database and undertaken by experts in the field, has concluded that the risk of adverse events after natural SARS-CoV-2 infection was substantially larger than that after Covid-19 vaccination – across all age groups.
The findings were published in the latest issue of the SA Medical Journal.
Although Covid-19 is no longer classed as a global health emergency, with vaccines having played an essential role in containing infection numbers and reducing the risk of severe disease, understanding their safety profile is crucial to guide response for future similar pandemics. With most studies showing they were generally safe, there have, however, been reports of adverse responses.
Using administrative data from Discovery, the researchers carried out an extensive study into the comparative risks associated with Covid-19 vaccination and SARS-CoV-2 infection after analysing a broad range of immune-mediated conditions.
The team – Karl Bernhardt, Shirley Collie, DWC Jacobs, Penelope Mekgwe, Glenda Gray, Jonny Peter and Linda-Gail Bekker – write that understanding the safety profile of the vaccines remains vital, particularly in the context of the continued rise of vaccine misinformation and denialism.
Study limitations
As an analytical retrospective cohort study, they wrote that this research identifies associations rather than proves causal relationships between vaccination, infection and subsequent adverse events. Even with comprehensive matching to control for confounding, the potential influence of unmeasured factors cannot be entirely excluded.
While the study analysed extensive data and a large variety of conditions using the WHO’s ICD-10 codes, the data records lack clinical validation, and certain cohorts, like the AD26.COV2 vaccine analysis, were relatively small. So rare conditions might not have been identified as having an increased risk, because the sample size might not have been sufficient to detect less common adverse events.
Due to the differing regimen sizes, a direct comparison between vaccine types was not feasible. The study’s objective was not to assess the effectiveness of any specific vaccine regimen, but to evaluate the relative difference in adverse events after vaccination v SARS-CoV-2 infection.
Although the study population is diverse in race and socioeconomic status, results may not be generalisable to the full uninsured SA population.
Study details
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
K Bernhardt, Collie, DWC Jacobs, P Mekgwe, G Gray, J Peter, LG Bekker.
Published in the SA Medical Journal in June 2026
Abstract
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 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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