COVID-19 Vaccine Safety Studies among Vulnerable Populations: A Systematic Review and Meta-analysis of 120 Observational Studies and Randomized Clinical Trials

BACKGROUNDThe COVID-19 vaccines were rapidly developed and tested, but concerns about vaccine-related adverse events remain, especially in vulnerable groups like pregnant women, children, and those with certain health conditions. This review aims to summarize rates of such adverse events in individuals often not included in randomized clinical trials (RCT). METHODFrom December 2019 to February 2022, we searched Embase and Medline for observational studies and RCTs on adverse events post-COVID-19 vaccination in vulnerable groups. We examined serious and non-serious events in individuals with specific medical conditions, infants, children, pregnant individuals, and socioeconomically disadvantaged individuals. Cumulative risks for all events were calculated. The Incidence rate (IR) and 95% confidence intervals were reported for those studies that met the follow-up period criteria based on the referenced literature. For events with data on exposed and unexposed groups, we calculated the odds ratio. Pooled incidence rates were calculated per 1000 person-days using a random-effects model. Sub-group analyses were conducted based on vaccine types and doses, with heterogeneity assessed using I2. FINDINGSOf the 4,254 papers, 235 met eligibility criteria, including 120 studies with 171,073 participants (113 observational, eight RCTs. We examined 17 severe and 7 non-severe adverse event categories. Lymphadenopathy (IR: 1.95[1.20;3.19]), autoimmune disease and multiple sclerosis flare-up (1.13 [0.47;2.68]), and cardiac symptoms (0.26[0.00;10.58]) were the most severe events. Allergic reactions were more common among autoimmune (7.03[4.10;12.06]) and cancer (4.87[2.21;10.76]) groups. vaccinees who received the second dose of vaccine had higher proportions of disease flare-ups (39.27 [18.08;85.31] vs 22.13 [10.22; 47.93]); cardiac symptoms (6.11[2.05-18.22] vs 3.78[2.53-5.65]); and cardiac events (5.34[1.69;16.90] vs 5.05[1.40,18.19]) in observational studies. INTERPRETATIONThis review highlights COVID-19 vaccine safety in vulnerable populations, enhancing vaccination strategies. Further real-world research is needed to validate and extend our findings, especially in addressing safety gaps among vulnerable groups.