By Stan Deresinski, MD, FIDSA, FACP
Respiratory syncytial virus, influenza, and COVID-19 vaccines are safe and effective.
Scott J, Abers MS, Marwah HK, et al. Updated evidence for Covid-19, RSV, and influenza vaccines for 2025-2026. N Engl J Med. 2025; Oct 29. doi: 10.1056/NEJMsa2514268. [Online ahead of print].
Scott and colleagues have performed an extensive and remarkable systematic review and meta-analysis of clinical data to provide timely data informing current practice. This has become critical because it corrects the
current wave of misinformation, some of which has come from U.S. government officials, about COVID-19, respiratory syncytial virus (RSV), and influenza vaccines.
Overall, after screening 17,263 references, they identified 511 eligible studies, of which 12% were randomized controlled trials, 24% were cohort studies, 16% were case control studies, and 48% were observational with other designs. Only data published since the most recent Association for Professionals in Infection Control and Epidemiology (APIC) reviews were included.
The analysis found that COVID-19 vaccines had effectiveness against hospitalization of 46% to 68%, and 37% in immunocompromised adults. For RSV, maternal vaccination, infant nirsevimab administration, and vaccination of adults > 60 years of age had effectiveness against hospitalization that was > 68%. The pooled effectiveness of influenza vaccine against hospitalization in adults ages 18-64 years was 48% and was 67% in children.
No new safety signals of concern were identified. Myocarditis occurred in male adolescents at frequencies of 1.3 to 3.1 per 100,000 doses of COVID-19 vaccine doses. However, there was no statistically significant association with myocarditis/pericarditis with the newer XBB.1.5-containing messenger ribonucleic acid (mRNA) vaccines. After receipt of the RSVpreF vaccine, older adults had 18.2 excess cases of Guillain-Barré syndrome per million doses. Of note is that preterm births were not increased in association with administration of the vaccine at 32-36 weeks of gestation. Overall, it is unequivocally clear that the benefit of all three vaccines vastly outweighs the risk of any significant adverse effect.
Commentary
Responding to the confusion regarding vaccination guidance resulting from federal actions, Scott and his colleagues took only 12 weeks to develop and publish this comprehensive independent evidence assessment in time for the 2025-2026 respiratory virus season. The results confirm the effectiveness of these vaccines. In addition, they were safe, although there was a possible modest risk of myocarditis in young males after COVID-19 vaccination and of Guillain-Barré syndrome after RSVpreF vaccination. Of note is that myocarditis occurring after COVID-19 vaccination is associated with fewer cardiovascular complications than it is when occurring after COVID-19.1
Thus, this remarkable effort validates the effectiveness and safety of immunizations against RSV, influenza, and COVID-19 and also validates the application of this information in the promotion of public health. It also provides a remarkable example of independent collaboration in provision of guidance at a time in which governmental institutions have failed.
This is a very brief summary of some of the high points of this publication, which has a wealth of information, and I encourage readers to explore the full text for themselves.
Stan Deresinski, MD, FACP, FIDSA, is Clinical Professor of Medicine, Stanford University.
Reference
1. Semenzato L, Le Vu S, Botton J, et al. Long-term prognosis of patients with myocarditis attributed to COVID-19 mRNA vaccination, SARS-CoV-2 infection, or conventional etiologies. JAMA. 2024;332(16):1367-1377.
