- Design
- systematic review of trials, comparative observational studies and safety studies
- Population
- 155 eligible publications on US-licensed COVID-19 vaccines and US SARS-CoV-2 epidemiology
- Primary outcome
- vaccine effectiveness against COVID-19 hospitalisation and severe outcomes, and safety
- Effect
- hospitalisation VE 53.0% (95% CI 37.0–65.0) in ≥65s and 54.0% (1.0–78.0) in 18–64s; paediatric ED visits 76.0% (58.0–87.0)
This systematic review searched four databases from August 2025 to June 2026 for studies on US-licensed COVID-19 vaccines, and included 155 publications: 15 randomised trials, 84 comparative observational studies, 38 single-group safety studies and 18 burden descriptions.
Updated vaccines were associated with reduced hospitalisation in adults aged 65 and over (vaccine effectiveness 53.0%, 95% CI 37.0 to 65.0, for the 2025-2026 season) and in adults aged 18 to 64 (54.0%, 1.0 to 78.0, for 2024-2025). Vaccination during pregnancy was associated with fewer COVID-19 emergency department or urgent care encounters in the vaccinated person (58.0%, 24.0 to 77.0) and fewer COVID-19 hospital contacts in their infants during the first two months of life (50.0% to 54.0%), and trimester of vaccination did not appear to matter. In children aged 9 months to 4 years, effectiveness against COVID-19 emergency visits was 76.0% (58.0 to 87.0). In immunocompromised adults, effectiveness against ICU admission or death ranged from 32.0% to 53.0% depending on the condition. Healthcare workers who had received three to five doses were less likely than those with two to develop laboratory-confirmed illness (41.0%, 34.0 to 47.0) or post-acute symptoms (57.0%, 46.0 to 66.0).
Safety findings across events of special interest were consistent with previous reviews, and no study conducted under the extended primary-series dosing interval reported raised myocarditis or pericarditis risk. For a prescriber the practical content is the maternal and paediatric data: those are the groups where the conversation is hardest and where the numbers here are strongest.
- Offer vaccination in pregnancy at whatever trimester the patient presents — timing did not change infant protection
- Raise vaccination specifically with immunocompromised patients, where the endpoint prevented is ICU admission or death
- Check dose history in healthcare workers; three or more doses outperformed two
- Quote effectiveness against hospitalisation rather than against infection — that is what the evidence supports
Why it matters
The maternal and infant figures answer the question patients actually ask before accepting the vaccine in pregnancy.
Don't overread it
Almost all estimates are observational and US-based; they describe association with reduced hospitalisation rather than trial-proven efficacy.
The statistics, in plain English
The 18-to-64 interval of 1.0% to 78.0% is extremely wide — it just excludes zero, so the estimate is technically positive but carries almost no precision. The over-65 interval of 37 to 65% is far more reliable. Most of these are observational vaccine-effectiveness studies, which are vulnerable to confounding by who chooses vaccination, though test-negative designs mitigate some of it.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for infectious diseases, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free