Meta-analysis of COVID, RSV, flu vaccines for fall provides 'sea of data' showing efficacy, safety

The team found that XBB.1.5-adapted COVID-19 mRNA vaccines had a pooled vaccine effectiveness (VE) against hospitalization of 46% to 50% among adults and 37% in immunocompromised adults (those with weakened immune systems). A case-control study of KP.2-adapted COVID-19 vaccines showed a VE of 68%. 

"While these [COVID-19] effectiveness estimates are not the 90% or higher seen early in the pandemic against ancestral SARS-CoV-2, they represent meaningful protection against hospitalization and severe disease," said lead author Jake Scott, MD, clinical associate professor at Stanford University School of Medicine's infectious disease and geographic medicine division.

"These magnitudes are comparable to long-standing influenza vaccine performance," he added. "Even moderate effectiveness can avert large numbers of [hospital] admissions when circulation is high."

RSV prevention was especially strong, with pooled estimates of 68% for maternal vaccination protecting infants, 83% for the monoclonal antibody preventive nirsevimab in infants, and 79% for RSV vaccination against hospitalization in older adults. 

The pooled VE of the flu vaccine against hospitalization was 48% in adults and 67% in children across networks and countries.

Low risk of myocarditis, Guillain-Barre syndrome

Similar to previous evaluation findings, COVID-19 vaccine-associated myocarditis (inflammation of the heart muscle) occurred at rates of 1.3 to 3.1 per 100,000 doses in young males, with lower risks seen with longer dosing intervals. 

"Self-controlled analyses of the latest XBB.1.5-era formulations did not detect a significant myocarditis signal," Scott said. "Absolute risk are low."

Likewise, the risk of RSV vaccine-related Guillain-Barre syndrome (a peripheral nerve disorder) was low, with 18.2 excess cases per million doses in older adults. For maternal RSV vaccination, no link to preterm birth was seen when administered at 32 to 36 weeks' gestation. "This pattern warrants continued monitoring but does not change the overall benefit-risk balance, given the burden of severe RSV disease," Scott said.

Scott said the findings support coadministration of a COVID-19 and flu vaccine or RSV and flu vaccine, which can increase access and uptake. "Across studies of COVID plus influenza and RSV plus influenza vaccination, immunogenicity and safety were similar whether vaccines were given together or separately," he said.

Respiratory-virus vaccines 'cornerstone' of prevention

The VIP aims to inform—not make—policy, Dugdale said: "Our hope is that the various professional societies and public health organizations that are actively working on crafting guidance for the public about the use and safety of these vaccines can lean on the data that we've summarized that have emerged over the last year to 2 years on these three infections and their associated immunizations to be able to form the guidance that they're messaging to the public."

Laypeople can use the VIP's interactive web tool to look at the studies included in the systematic review and make informed vaccination decisions for themselves and their families. An August webinar by the team summarizing the evidence base for 2025-26 fall/winter vaccination is also available for viewing.

"These findings underscore the enduring value of respiratory virus immunization as a cornerstone of preventive care and support the feasibility of maintaining rigorous, evidence-based guidance during periods of institutional disruption," the authors concluded.

VIP spokesperson Kevin Griffis said the work of the VIP's Scientific Data Review team and its collaboration with medical professional societies shows how independent groups can work together to help ensure the public has the latest evidence-based immunization information and recommendations.

"The New England Journal paper is also an important data point—proof that if people are concerned about political interference in the systems and initiatives that we’ve relied on for decades to keep Americans safe from infectious diseases, we are not powerless," he said. "It's possible to take meaningful action and to fill gaps being created at the federal level."