Updated Evidence for Covid-19, RSV, and Influenza Vaccines for the 2025–2026 Season

Leon Wirz
Dec 8
5 min read

A comprehensive evidence review from NEJM (2025, December), Stanford University, University of Minnesota, Massachusetts General Hospital & partners

Introduction

Respiratory viruses continue to dominate winter disease burdens worldwide. Covid-19, RSV, and influenza still account for a large proportion of seasonal hospital admissions and ICU utilisation. While our immunity landscape continues to shift and viruses evolve, healthcare systems need solid, independent assessments of vaccine performance.

A new systematic review published in the New England Journal of Medicine evaluates 511 studies on the safety and effectiveness of respiratory virus vaccines for the 2025–2026 season.

The review stands out not just in scale, but in timing: as several countries face uncertainty in advisory processes, this analysis offers a stable, evidence-based framework. For Switzerland, where winter surges consistently strain hospitals and raise insurance expenditures, these insights matter.

The Core Discovery

Across all three virus families, one central message emerges:

Vaccines continue to substantially reduce the risk of severe disease and hospitalisation, and their safety profiles remain strong.

Updated Covid-19 vaccines (XBB.1.5 and KP.2), recently approved RSV immunisations (maternal vaccination, infant nirsevimab, and adult vaccines), and seasonal influenza vaccines all show protective effects in real-world settings. Severe adverse events remain rare and are far outweighed by the benefits.

In short: modern respiratory vaccines are performing as intended, even against evolving viral lineages.

How the Study Was Conducted

The authors conducted a systematic review and meta-analysis, screening over 17,000 publications and eventually including 511. These encompassed randomized controlled trials, cohort studies, case–control studies, and large national surveillance datasets.

The outcomes analysed covered hospitalisation, symptomatic infection, ICU admission, mortality, long-Covid symptoms, pregnancy outcomes, and adverse events such as myocarditis or Guillain–Barré syndrome. Random-effects models were used to pool estimates, and sensitivity analyses addressed potential bias.

Because the review included only studies published after the latest ACIP recommendations, it reflects the most current real-world vaccine performance.

Key Findings

Covid-19 Vaccines

Covid-19 vaccines adapted to XBB.1.5 subvariants showed moderate to high protection against hospitalisation across age groups. In adults, effectiveness against hospitalisation ranged from 46–50%, while adults aged 65+ benefited from around 56% protection. Immunocompromised adults saw somewhat lower protection at 37%, yet these reductions still translate to clinically meaningful risk reduction. One study of the KP.2-adapted vaccine reported 68% protection.

Safety data reinforce previous patterns. Myocarditis in male adolescents remains rare (1.3–3.1 per 100,000 doses) and appears strongly influenced by dosing intervals. Pregnancy outcomes showed no increased risks. In fact, several studies noted a lower risk of preterm birth among vaccinated individuals. Guillain–Barré syndrome was not consistently associated with Covid-19 vaccination.

RSV Immunisation

One of the strongest findings in the entire review concerns RSV prevention in infants. Both maternal RSVpreF vaccination and nirsevimab (a monoclonal antibody given to infants) demonstrated high effectiveness. Nirsevimab reduced hospitalisations by 79–83%, with similar reductions in ICU admissions. Maternal vaccination lowered infant RSV hospitalisations by 68%.

For adults aged 60+, RSV vaccines consistently showed around 79% effectiveness against hospitalisation.

Safety outcomes were reassuring: concerns about preterm birth were not confirmed when maternal vaccination occurred at the recommended gestational window (32–36 weeks). Among older adults, RSVpreF showed a small but measurable increase in Guillain–Barré syndrome (about 18 additional cases per million doses).

Influenza Vaccines

Influenza vaccines continue to perform reliably. In children, effectiveness against hospitalisation reached 67%, making flu vaccination one of the most impactful paediatric immunisations. Adults aged 18–64 saw 48% protection, while older adults benefitted especially from high-dose or adjuvanted formulations, which performed better than standard-dose vaccines.

Safety analyses again remained consistent across years: no elevated risks of miscarriage, congenital anomalies, stillbirth, or hypertensive disorders in pregnancy. Stroke or Guillain–Barré syndrome signals were not confirmed in high-quality analyses.

Limitations of the Study

Although broad, the review has limitations. Many included studies were observational, which introduces confounding despite sophisticated adjustments. Viral evolution means that effectiveness estimates may shift as new variants arise. The review also does not capture unpublished real-time surveillance data or studies outside the predefined time window.

Still, sensitivity analyses showed that results were robust even when excluding studies with moderate or high risk of bias.

Relevance for Switzerland

Switzerland faces recurring winter surges that burden hospitals, reduce workforce productivity, and drive up costs in basic health insurance. This review highlights several strategies with clear national relevance:

Maternal RSV vaccination and infant nirsevimab could substantially reduce paediatric winter admissions (a major challenge for Swiss children’s hospitals).
Annual Covid-19 and influenza vaccination in older adults helps stabilise ICU demand and reduce severe outcomes.
RSV vaccination for adults 60+ offers strong individual protection and reduces winter respiratory caseloads.
Coadministration (Covid + influenza + RSV in one visit) has proven safe and could improve uptake in pharmacies and GP practices.

Given Switzerland’s high healthcare costs (and the increasing financial strain on insurers) every prevented hospitalisation has concrete economic implications.

Potential Impacts of a Successful Therapy (i.e., High Vaccination Uptake)

If more people receive Covid-19, RSV, and influenza vaccines, the benefits show up quickly in everyday life.

For families with newborns, fewer infants would be hospitalised with RSV, meaning fewer emergency visits in the middle of the night and less time spent in overwhelmed paediatric wards.

Older adults would be less likely to end up in hospital with pneumonia or respiratory failure and could recover at home instead of facing prolonged rehabilitation stays.

Hospitals would experience fewer winter surges, allowing emergency departments to stay functional and reducing staff burnout.

Employers would see fewer sick days and less long-term absence, especially during peak winter months.

For Swiss insurers, each prevented hospitalisation (particularly an ICU stay) reduces substantial costs. And for society, higher vaccine uptake helps keep schools, workplaces, and the healthcare system running more smoothly through the winter season.

Risks

While vaccines remain overwhelmingly safe, the review confirms a few important but rare risks. Myocarditis after mRNA Covid-19 vaccination is primarily observed in adolescent males and remains dose-interval dependent. RSVpreF in older adults carries a small increase in Guillain–Barré syndrome, requiring continued monitoring. A small stroke signal after high-dose influenza vaccines observed in one dataset was not replicated elsewhere.

Overall, these risks remain low compared to the benefits of preventing severe respiratory illness.

Overall Assessment

The NEJM review provides one of the most comprehensive evaluations of respiratory virus vaccination to date. Its findings are clear: Covid-19, RSV, and influenza vaccines continue to offer strong protection against severe disease and maintain excellent safety profiles.

For Switzerland — where winter surges repeatedly test hospital resilience — these vaccines remain an essential component of public health planning and insurance cost containment.

What Comes Next

Future seasons will likely see updated Covid-19 formulations, broader adoption of maternal RSV vaccination across Europe, potential universal nirsevimab programmes for infants, and more structured triple-vaccine appointments in clinical settings. Additional European and Swiss-specific effectiveness data will further refine national vaccination strategies.

Reference

Scott J, Abers MS, Marwah HK, McCann NC, Meyerowitz EA, Richterman A, Fleming DF, Holmes EJ, Moat LE, Redepenning SG, Smith EA, Stoddart CJ, Sundaram ME, Ulrich AK, Alba C, Anderson CJ, Arpey MK, Borre E, Ladines-Lim J, Mehr AJ, Rich K, Watts C, Basta NE, Jarolimova J, Walensky RP, Dugdale CM. Updated Evidence for Covid-19, RSV, and Influenza Vaccines for 2025-2026. N Engl J Med. 2025 Dec 4;393(22):2221-2242. doi: 10.1056/NEJMsa2514268. Link