What the Latest Evidence Says About Flu, COVID-19 and RSV Vaccines

Although the toll of respiratory illness has changed since the height of the COVID-19 pandemic, influenza, COVID-19 and respiratory syncytial virus (RSV) continue to drive hundreds of thousands of hospitalizations in the U.S. each year, according to new evidence reviews from the Vaccine Integrity Project (VIP), based at the University of Minnesota’s Center for Infectious Disease Research and Policy (CIDRAP). With the fall and winter respiratory virus season approaching, the findings arrive at a timely moment for clinicians and patients weighing immunization decisions ahead of peak transmission months.

Interim Centers for Disease Control and Prevention estimates put influenza-related hospitalizations during the 2025-2026 season at more than 390,000, with roughly 24,000 deaths. COVID-19, while substantially less severe than during the pandemic’s peak, still contributed an estimated 4.6 million to 12.9 million illnesses and 15,000 to 42,000 deaths over the same period, with the peak weekly hospitalization rate roughly 80% below the 2022-2023 peak. RSV caused an estimated 170,000 to 340,000 hospitalizations and as many as 25,000 deaths, continuing to pose the greatest risk to infants and older adults.

Influenza Vaccine Data

After screening more than 5,800 studies, researchers identified 69 newly published studies, including 21 randomized controlled trials, supporting continued reductions in hospitalization and mortality among high-risk groups. Among adults older than 65, flu vaccination increased protection against hospitalization by 31%, according to VISION Network data. A multiseason case-cohort analysis found 80% vaccine effectiveness against laboratory-confirmed influenza-associated deaths in children and infants aged 6 months to 17 years, while vaccination during pregnancy improved protection against symptomatic disease in infants 0 to 6 months by 44%. High-dose flu vaccines showed greater protection against hospitalization in older adults compared with standard-dose formulations. No new safety concerns emerged, including among nearly 10 million people evaluated through postmarketing surveillance.

COVID-19 Vaccine Data

Researchers screened more than 11,000 studies and included 155 in the review. Updated COVID-19 vaccines continued to show meaningful protection against severe outcomes: a 53% reduction in hospitalization risk for adults older than 65, a 58% reduction in emergency and urgent care visits for pregnant women (with extended protection to infants), and a 76% reduction in COVID-19-related pediatric emergency room visits for children aged 9 months to 4 years. For immunocompromised adults, vaccination cut the risk of ICU admission or death by 32% to 53%, depending on the condition. No new safety concerns were identified in comparative studies, though researchers noted that postmarketing surveillance data lacked comparison groups needed to determine whether adverse events occurred more frequently than expected without vaccination.

RSV Vaccine Data

Out of more than 2,000 studies assessed, 75 met eligibility criteria for the RSV review. Vaccination among older adults and pregnant women, along with infant immunization using the monoclonal antibody nirsevimab, substantially reduced severe RSV illness. Adults older than 60 saw vaccine effectiveness against hospitalization ranging from 69% to 83% within the same season as vaccination, while maternal vaccination reduced infant hospitalization risk by 51% to 70%. Nirsevimab reduced RSV-related hospitalization risk in infants by 63.6% to 93.0% within their first RSV season, regardless of timing. No new safety concerns were identified, and none of the comparative studies found an association between RSV vaccination during pregnancy and preterm birth or other adverse pregnancy outcomes.

Researchers noted that questions remain about whether older adults may benefit from an RSV booster, with mixed findings on whether protection wanes meaningfully between the first season after vaccination and the 12- to 18-month mark.

A Commitment to Evidence-Based Guidance

The reviews used prospectively registered protocols and internationally recognized systematic review methods, with researchers independently screening studies and assessing quality and bias before synthesizing findings. “Our objective is straightforward: Provide clinicians and medical societies with a transparent, rigorous assessment of the latest evidence so immunization recommendations remain grounded in the best available science,” said Michael Osterholm, Ph.D., M.P.H., director of CIDRAP.