Summary
A medRxiv preprint estimates that PCV20 was 20.4% effective against culture-confirmed pneumococcal pneumonia hospitalisations among U.S. adults aged 65 and older. Effectiveness was higher in the Western region, where the study identified a high burden of serotype 4 disease.
A retrospective U.S. Veterans Affairs study posted as a medRxiv preprint estimates that the 20-valent pneumococcal conjugate vaccine (PCV20) provided 20.4% effectiveness against hospitalisation for culture-confirmed pneumococcal pneumonia among adults aged 65 and older. The estimate was higher among older adults with chronic medical conditions and in the Western U.S. region.
The study used a test-negative design and covered 34,009 pneumonia hospitalisations between January 2023 and December 2025. Because the research is a preprint based on existing health records, its findings are observational estimates for the Veterans Affairs population included in the analysis.
Contents
What the study measured
PCV20 is designed to protect against 20 serotypes of Streptococcus pneumoniae, the bacterium responsible for pneumococcal disease. In this study, researchers examined adults aged 18 and older who were hospitalised with pneumonia in the U.S. Veterans Affairs Healthcare System and had respiratory cultures collected.
Of the 34,009 hospitalisations, 837, or 2.5%, had cultures positive for S. pneumoniae. A total of 7,428 people, or 21.8% of the study population, had received PCV20.
A test-negative design compares patients who have the illness being studied and test positive for the target infection with similar patients who test negative. Here, the researchers compared culture-confirmed pneumococcal pneumonia hospitalisations with pneumonia hospitalisations without a positive pneumococcal culture, then estimated vaccine effectiveness using multivariable logistic regression. The analysis was adjusted for demographic and clinical characteristics.
The researchers also performed subgroup analyses by age, risk group and U.S. census region. An inverse probability of treatment weighting analysis, used as a sensitivity analysis, produced findings consistent with the main analysis.
Effectiveness was higher in older adults
Among adults aged 65 and older, PCV20 vaccination was associated with an estimated vaccine effectiveness of 20.4% against culture-confirmed pneumococcal pneumonia hospitalisation. The 95% confidence interval was 2.1% to 35.3%.
The estimate was 24.4% among older adults with chronic medical conditions, with a 95% confidence interval of 0.7% to 42.4%.
Across all adults aged 18 and older, estimated effectiveness was 8.8%, with a 95% confidence interval ranging from −8.8% to 23.6%. This wider interval crossed zero, making the overall estimate less precise than the estimate for adults aged 65 and older.
These figures describe vaccine effectiveness against a specific outcome: hospitalisation for pneumonia confirmed by respiratory culture as pneumococcal. They are not estimates of protection against every cause of pneumonia.
Why regional serotypes matter
The strongest regional estimate among adults aged 65 and older was recorded in the Western U.S., where estimated effectiveness was 39.6%, with a 95% confidence interval of 3.2% to 62.3%. The study identifies that region as having a high burden of serotype 4 disease.
Pneumococcal vaccines target specific bacterial serotypes rather than every possible strain. As a result, the proportion of disease caused by vaccine-covered serotypes can influence the protection observed in a population. The regional pattern in this analysis supports the authors’ conclusion that vaccination strategies should account for local serotype distribution when estimating public-health impact.
The study’s design and population are important for interpreting the results. It was a retrospective analysis of existing Veterans Affairs health records, limited to adults hospitalised with pneumonia who had respiratory cultures collected. The preprint therefore provides an effectiveness estimate for this tested hospital population, rather than a result from a prospective randomised vaccine trial or a direct estimate for all adults.