Three-year longitudinal safety surveillance following COVID-19 vaccination in individuals with underlying medical conditions

Individuals with chronic comorbidities are at increased risk of severe COVID-19 outcomes. Although post-vaccination adverse events are generally mild and comparable to those in the general population, rare events and limited longitudinal data highlight the need for condition-specific long-term safety surveillance. To address these critical evidence gaps, this study conducted a longitudinal analysis of various COVID-19 vaccine platforms within the Iranian population with comorbidities three years post - vaccination. The research evaluated the safety profiles of different vaccine platforms across these patient cohorts using a researcher-made questionnaire composing of short-term and long-term vaccine adverse events as well as cases’ medical profiles. Furthermore, an exploratory immunogenicity sub-study was performed among participants with HIV to characterize vaccine-induced humoral immune responses. A total of 1115 participants were enrolled; 43.9% had a history of COVID-19 infection, with significantly higher incidence among participants with several comorbidities. Body pain, fever, and weakness were the most frequently reported early adverse events (AEs). During long-term follow-up, 23.8% experienced at least one post-vaccination event, most commonly cardiovascular (5.4%) and neurological (4.8%) conditions. Multiple analysis identified obesity and liver disease as the strongest independent risk factors for a broad range of AEs, while increasing age was associated with higher odds of overall and several organ-specific events. After adjustment for age, sex, previous COVID-19 infection, and number of comorbidities, AstraZeneca recipients had higher rates of early AEs after the first dose and first booster. PastoCovac and Sputnik were associated with lower odds of early AEs after the second dose, whereas Bharat, Barkat, and PastoCovac were associated with higher odds of late AEs. While AEs were frequent in cases with underlying conditions, most of them were mild and transient. However, cardiovascular and neurological symptoms were the most frequently reported long-term events during follow-up. Although some kinds of comorbidities showed a higher prevalence of complains after specific vaccine types, the casual association is not possible yet.