This systematic review evaluated the effectiveness and safety of US-licensed COVID-19 vaccines across multiple populations (older adults, adults 18–64, pregnant women, infants, immunocompromised adults, healthcare personnel, and children 9 months–4 years), covering studies published from August 1, 2025 through June 29, 2026.
Updated COVID-19 vaccines reduced hospitalization risk in older adults (VE 53%, 95% CI 37%–65%) and adults 18–64 (VE 54%, 95% CI 1%–78%); maternal vaccination cut infant COVID-19 hospital contacts in the first 2 months of life (VE 50%–54%); vaccination reduced pediatric ED visits in ages 9 months–4 years (VE 76%, 95% CI 58%–87%); and 3–5 doses vs. 2 doses in healthcare personnel reduced confirmed COVID-19 (VE 41%) and post-acute symptoms (VE 57%). No new safety signals were identified.
Wide confidence intervals for adults 18–64 (VE 95% CI 1%–78%) suggest imprecision; most effectiveness estimates come from observational studies subject to confounding; findings reflect US-licensed vaccines and may not generalize globally.
Clinicians should encourage updated COVID-19 vaccination across all high-risk groups—including pregnant patients, young children, older adults, and the immunocompromised—as effectiveness against hospitalization and severe illness remains consistent and no new safety signals have emerged. Healthcare personnel benefit from additional doses beyond the primary series, with meaningful protection against both acute illness and post-acute symptoms.
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