COVID-19 Vaccine Effectiveness and Safety for the 2026-2027 Respiratory Season

SARS-CoV-2 remains a substantial cause of respiratory illness, morbidity, and mortality. Evidence to date has demonstrated that COVID-19 vaccines reduce the risk of severe disease, including hospitalization and death.

This systematic review identifies and summarizes newly published studies reporting on the effectiveness and safety of COVID-19 vaccines and COVID-19 epidemiology in the US.

Cochrane Central Register of Controlled Trials, PubMed/MEDLINE, Embase, and Scopus were searched from August 1, 2025, through June 29, 2026. Studies were eligible if they reported on the effectiveness, efficacy, or safety of a US-licensed COVID-19 vaccine or SARS-CoV-2 epidemiology in the US.

From 11 829 identified references, 155 publications were eligible (15 randomized clinical trials, 84 observational studies with a comparator group, 38 product safety studies without a comparator group [single group], and 18 descriptive studies of disease burden). Consistent with prior evidence, studies reported that updated COVID-19 vaccines were associated with a reduction in the risk of hospitalization among both older adults (≥65 years; vaccine effectiveness [VE], 53.0%; 95% CI, 37.0%-65.0%; 2025-2026 season) and adults (18-64 years; VE, 54.0%; 95% CI, 1.0%-78.0%; 2024-2025 season). Maternal vaccination was associated with reduced risk of COVID-19-associated emergency department/urgent care encounters among individuals vaccinated (VE, 58.0%; 95% CI, 24.0%-77.0%) and with fewer COVID-19-related hospital contacts in the first 2 months of life among infants born subsequently (VE range, 50.0%-54.0%), regardless of trimester of vaccination. Vaccination was also associated with a significant reduction in COVID-19-related pediatric emergency department visits (9 months to 4 years; VE, 76.0%; 95% CI, 58.0%-87.0%). Vaccination was associated with a reduced risk of critical COVID-19 illness (intensive care unit admission or death) in immunocompromised adults (VE range, 32.0%-53.0%, depending on condition and other factors). Health care personnel who received 3 to 5 vaccine doses were less likely to develop laboratory-confirmed COVID-19 illness (VE, 41.0%; 95% CI, 34.0%-47.0%) and postacute COVID-19 symptoms (VE, 57.0%; 95% CI, 46.0%-66.0%) compared with those who received only 2 doses. Across adverse events of special interest (eg, stroke, thrombosis, myocarditis), safety profiles were consistent with those of previous reviews. No identified studies conducted under the updated guidance on extended dosing intervals for the primary series reported an increased risk of myocarditis or pericarditis. No new safety signals were reported in the recently published studies eligible for this updated review of US-licensed COVID-19 vaccines.

COVID-19 vaccines were consistently associated with a reduction in the risk of hospitalization and other outcomes, including among individuals at high risk of severe COVID-19, such as infants, and those who were pregnant. No new safety concerns were identified.