CVR - Coronavirus Vaccines R&D Roadmap

• Influenza, COVID-19 and respiratory syncytial virus (RSV) continue to cause substantial illness, hospitalization and death in the United States, with the greatest risk of severe disease concentrated among older adults, infants, pregnant women, people with underlying health conditions and those who are immunocompromised.
• The Vaccine Integrity Project conducted three reviews of newly published evidence on the epidemiology, effectiveness and safety of U.S.-licensed influenza, COVID-19 and RSV immunizations. Together, the reviews identified 299 eligible studies published primarily between August 2025 and June 2026.
• The newest evidence continues to demonstrate that immunization provides meaningful protection against hospitalization, severe illness and death. The degree of protection varies by virus, vaccine or immunization product, population, season and circulating strains.
• No new safety concerns were identified in comparative studies evaluating currently recommended immunizations. The findings are consistent with the well-established safety profiles of influenza and COVID-19 vaccines and the growing safety evidence for RSV immunizations.
• The updated evidence was provided to leading medical societies to inform their 2026–2027 respiratory virus immunization recommendations.

Influenza, COVID-19 and RSV remain important causes of respiratory illness in the United States. Although COVID-19 is causing substantially less severe disease than during the height of the pandemic, all three viruses continue to cause hundreds of thousands of hospitalizations each year.

During the 2025–2026 season, CDC estimates indicated that influenza was associated with 390,000-800,000 hospitalizations. COVID-19 hospitalization rates continued their decline from previous seasons, but the highest hospitalization rates remained concentrated among older adults and infants. RSV was associated with an estimated 2.8 million to 5.8 million outpatient visits, 170,000 to 340,000 hospitalizations and 9,900 to 25,000 deaths, according to CDC data.

The Vaccine Integrity Project assembled a multidisciplinary team of researchers and public health experts to update its 2025 evidence review of respiratory virus immunizations. Researchers systematically searched major scientific databases for peer-reviewed studies examining disease epidemiology and the effectiveness and safety of U.S.-licensed influenza, COVID-19 and RSV vaccines and immunizations.

The reviews followed PRISMA reporting standards, and protocols were prospectively registered with PROSPERO. Study selection, data extraction and assessment of risk of bias were performed independently by two researchers, with disagreements resolved through discussion or review by a third researcher. Randomized controlled trials and comparative observational studies were assessed using internationally recognized risk-of-bias tools.

From among thousands of papers screened by the Vaccine Integrity Project, the influenza review identified 69 eligible studies, the COVID-19 review identified 155, and the RSV review identified 75.

Updated COVID-19 vaccines continued to provide meaningful protection against hospitalization and other serious outcomes. Benefits were evident across age groups and were particularly important for people at increased risk of severe disease.

Older adults: During the 2025–2026 season, updated COVID-19 vaccination was 53% effective against hospitalization among adults age 65 and older. This protection is particularly important because older adults continue to experience the highest rates of COVID-19 hospitalization.

Infants and children: Vaccination was associated with a 76% reduction in COVID-19-related emergency department visits among children ages 9 months through 4 years. Vaccination during pregnancy also extended protection to newborns, reducing COVID-related hospital contacts among infants during their first two months of life by approximately 50%-54%.

Pregnancy: Vaccination during pregnancy was 58% effective against COVID-19-related emergency department or urgent care visits among pregnant women. Protection for infants was observed regardless of the trimester in which vaccination occurred. Recent evidence also found no association between maternal COVID-19 vaccination and stillbirth and no increased risk of other adverse pregnancy outcomes, including preterm birth.

Adults: Updated vaccination reduced hospitalization among adults ages 18 through 64 by approximately half in a study from the 2024–2025 season. 

People who are immunocompromised: Vaccination continued to provide meaningful, although generally lower, protection among people with immunocompromising conditions. Studies found reductions in severe outcomes, including hospitalization, intensive care admission and death, with effectiveness varying according to the underlying condition and other factors.

Safety: Comparative studies identified no new safety concerns. Previously identified myocarditis and pericarditis risks – seen primarily in adolescent and young adult males following earlier mRNA vaccine schedules – led to changes in recommended dosing intervals in 2022. The current review identified no studies enrolling participants exclusively after that schedule change that reported an increased frequency of myocarditis. Studies also did not identify increased risks of stroke or thrombotic events.

The review also included post-marketing and other safety studies without comparison groups. Some reported adverse events occurring after vaccination, but without an appropriate comparator group, these studies cannot determine whether events occurred more frequently than would otherwise be expected or whether vaccination caused them.

The rapidly growing evidence base for RSV immunization continues to demonstrate substantial protection against severe illness and hospitalization among older adults and infants. Evidence also supports vaccination during pregnancy as an effective strategy for protecting newborns.

Older adults: Across multiple studies, RSV vaccination among adults age 60 and older was 69% to 83% effective against RSV-related hospitalization. Evidence on how long protection lasts continues to develop. One study reported lower estimates of effectiveness 12 to 18 months after vaccination compared with the first RSV season, while another did not find a significant difference. Additional evidence is needed to determine whether and when older adults may benefit from additional doses.

Pregnancy and infants: Maternal RSV vaccination administered between 32 and 36 weeks of pregnancy was 51% to 70% effective against RSV-related hospitalization in infants. None of the comparative studies included in the review found an association between maternal RSV vaccination and preterm birth or other adverse pregnancy outcomes.

Infant immunization: The long-acting monoclonal antibody nirsevimab provided particularly strong protection during infants’ first RSV season. Studies found nirsevimab reduced the risk of emergency department consultations by 86% to 97% and RSV-related hospitalization by approximately 66% to 93% within six months after immunization.

People at increased risk: RSV immunizations were also associated with protection among people with immunocompromising conditions and other health conditions that increase the risk of severe RSV, although the amount of protection varied across populations.

Safety: Newly published evidence was consistent with previous safety assessments, and no new safety signals were identified. No cases of Guillain-Barré syndrome were reported across three randomized controlled trials. One observational self-controlled case series reported a possible increased risk of Guillain-Barré syndrome among older adults during the 42 days following vaccination, consistent with a safety signal identified in previous evaluations and warranting continued monitoring.

Seasonal influenza vaccination continued to reduce severe disease, hospitalization and death, particularly among people at greatest risk for serious infection.

Older adults: Multiple studies found meaningful protection against hospitalization among adults age 65 and older. An analysis using VISION Network data found vaccination provided 31% protection against influenza-associated hospitalization, and it reduced the hospitalization risk by 43 percent, according to a study from 2022-2024. Newly published randomized trial data also showed greater protection against hospitalization from high-dose influenza vaccine compared with standard-dose vaccine in older adults.

Infants and children: Vaccination was associated with substantial protection against severe pediatric influenza. An analysis of national surveillance data covering eight influenza seasons found vaccine effectiveness of 80% against laboratory-confirmed influenza-associated death among children and adolescents. Among children ages 6 months through 17 years with underlying medical conditions, vaccination was 48% effective against influenza-related hospitalization or emergency department visits.

Pregnancy: Vaccination during pregnancy provided protection to infants during the first months of life, when they are too young to receive influenza vaccine themselves. A study using data from 2011 through 2022 found maternal vaccination was 44% effective against symptomatic influenza in infants through 6 months of age.

Safety: No new safety concerns were identified. A large post-marketing analysis involving nearly 10 million vaccinated people found no increased risk of serious adverse events, including Guillain-Barré syndrome, following seasonal influenza vaccination or when influenza vaccine was administered with COVID-19 or RSV immunizations. Another study found no statistically significant increased risk of febrile seizures in children following vaccination.

The latest evidence reinforces the findings of the Vaccine Integrity Project’s previous review: influenza, COVID-19 and RSV immunizations continue to provide meaningful protection against severe disease, hospitalization and death, with reassuring safety profiles.

The evidence is particularly strong for populations most vulnerable to severe respiratory disease. Influenza vaccination reduces hospitalization and mortality among older adults and protects children against severe and fatal disease. Updated COVID-19 vaccines continue to reduce hospitalization and other serious outcomes, including among older adults, young children, pregnant people and those who are immunocompromised. RSV vaccination and infant monoclonal antibody immunization substantially reduce RSV-related hospitalization among older adults and infants.

The evidence also underscores that respiratory virus immunization is not one-size-fits-all. Effectiveness varies according to age, underlying health conditions, circulating viruses, vaccine formulation and time since immunization. Emerging questions, including the duration of RSV vaccine protection in older adults, require continued study.

Taken together, however, the newest evidence remains consistent with the larger body of research supporting respiratory virus immunization. No new safety concerns were identified in comparative studies, and the benefits of immunization remain greatest for people at highest risk of severe disease.

These findings provide the scientific foundation for respiratory virus immunization recommendations from leading U.S. medical societies for the 2026–2027 season.