Backed by real-world evidence from more than 500 studies, a new review shows that this season’s Covid-19, RSV, and flu vaccines continue to protect against severe illness.
Study: Updated Evidence for Covid-19, RSV, and Influenza Vaccines for 2025–2026. Image credit: Tong_stocker/Shutterstock.com
A systematic review of U.S.-licensed immunizations against respiratory viruses has recently been done to provide updated evidence on vaccine efficacy and safety and to inform immunization guidance during the 2025–2026 season. The findings are published in The New England Journal of Medicine.
Vaccine guidance needs clarity
Three predominantly circulating respiratory viruses in the U.S. are severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV), and influenza. These viruses are associated with significant morbidity and mortality, with hospitalization rates varying according to viral evolution and changes in population immunity.
In the U.S, the rate of hospitalization due to respiratory infections was highest for SARS-CoV-2 during the 2023–2024 season, followed by influenza and RSV. The risk of hospitalization for SARS-CoV-2 infection remained significantly higher for older adults and very young children since the onset of the coronavirus disease 2019 (COVID-19) pandemic. The risk of RSV-related hospitalization remained highest in 2023–2024 among children under five years of age.
Recent changes in the vaccine advisory process in the U.S. have disrupted immunization guidance, underscoring the need for updated evidence on vaccine efficacy and safety.
The current systematic review aimed to provide recent information on the epidemiology of respiratory viruses and the efficacy and safety of vaccines. The primary objective was to provide healthcare professionals with timely evidence for the 2025–2026 respiratory virus season.
Data behind vaccine decisions
The systematic review included U.S.-based randomized controlled trials and observational studies that investigated the epidemiology of SARS-CoV-2, RSV, and influenza viruses, as well as the efficacy and safety of vaccines targeting these viruses.
In total, 17,263 references were screened, and 511 studies met the inclusion criteria. The primary outcomes of the review were vaccine efficacy against virus-related hospitalization and other clinical parameters, as well as vaccine safety.
Vaccines still prevent severity
The study analysis reconfirmed that COVID-19, RSV, and influenza vaccines can effectively reduce the risk of severe infection and related hospitalization across populations.
COVID-19 vaccine efficacy
According to the recent estimates, the efficacy of the COVID-19 vaccine against hospitalization due to a highly transmissible subvariant of the omicron strain (XBB.1.5) was 46% among adults and 37% among immunocompromised adults. Such moderate-to-high vaccine efficacy was observed across age groups, and it remained substantial within six months after vaccination.
However, the vaccine targeting this subvariant showed lower efficacy (14 % to 54 %) during the circulation of the newer JN.1 omicron subvariant, highlighting the need for continuous viral surveillance and the timely development of strain-specific vaccines.
In a case–control study, the BNT162b2 vaccine adapted to the KP.2 subvariant showed 68 % effectiveness against hospitalization. The study analysis also revealed an association between COVID-19 vaccination and a reduced risk of long COVID among children.
RSV vaccine efficacy
All types of RSV vaccines showed substantial efficacy in preventing adverse outcomes. Specifically, maternal RSV vaccination for infant protection, monoclonal antibody treatment (nirsevimab) for infants, and RSV vaccination for older adults showed an efficacy of 68 % or more against hospitalization.
A relatively lower but substantial vaccine efficacy (approximately 70% to 73%) against hospitalization was observed among immunocompromised adults.
Influenza vaccine efficacy
Influenza vaccines showed efficacy against both symptomatic infection and hospitalization across all age groups. Specifically, the vaccine efficacy against hospitalization was 48% among adults and 67% among children. Moreover, added benefits were observed among older adults who received the recommended high-dose formulations, which achieved higher protection (up to 53%) compared with standard-dose vaccines (36–47%).
COVID-19 vaccine safety profile
The analysis of recent studies indicated that COVID-19 vaccination during pregnancy is associated with a lower risk of preterm birth. However, no association was observed with miscarriage, congenital anomalies, or stillbirth.
Myocarditis (inflammation of the heart muscle) was identified as a potential vaccine-related adverse event, occurring at rates of 1.3 to 3.1 per 100,000 doses in adolescents, with longer dosing intervals associated with a substantially lower risk.
RSV vaccine safety profile
RSV vaccination showed no significant associations with pregnancy-related hypertensive disorders, stillbirth, or congenital anomalies in randomized trials and real-world studies. Although initial evidence linked RSV vaccines to preterm birth risk, it was observed subsequently that vaccination received at 32 to 36 weeks of gestation is not associated with an increased risk.
In older adults aged 60 years or above, RSV vaccination was associated with a significantly higher risk of Guillain–Barré syndrome, a rare neurological disorder characterized by muscle weakness and numbness. However, such risk remained rare in other age groups.
Influenza vaccine safety profile
Influenza vaccines showed an excellent safety profile across age groups and during pregnancy, with a substantial number of studies showing lower risks of miscarriage, preterm birth, and congenital anomalies following vaccination.
Vaccines remain our best defense
This systematic review provides updated and independent evidence on the safety and efficacy of vaccines against respiratory viruses that are predominantly circulating in the U.S. The findings highlight the enduring value of vaccination and support the practicability of maintaining rigorous, evidence-based guidance during periods of institutional disruption.
Notably, this systematic review demonstrates that available evidence supports the safety and effectiveness of co-administration of COVID-19, RSV, and influenza vaccines, with outcomes comparable to separate administration. However, evidence on this point remains limited and is based primarily on small studies. This finding supports single-visit vaccination strategies to facilitate access.
Download your PDF copy now!
Influenza infection in pregnant mice linked to fetal brain exposure