Effectiveness of 20-valent pneumococcal conjugate vaccine against pneumococcal pneumonia hospitalizations among U.S. adults: Test-Negative Design
- 1University of Rhode Island and Providence Veterans Affairs Healthcare System
Abstract
ObjectiveThis study estimated the vaccine effectiveness (VE) of 20-valent pneumococcal conjugate vaccine (PCV20) against culture-confirmed pneumococcal pneumonia hospitalizations among adults using a test-negative case-control design.
MethodsWe included adults ([≥]18 years) hospitalized with pneumonia in the U.S. Veterans Affairs Healthcare System between January 2023 and December 2025 who had respiratory cultures collected. VE was estimated using multivariable logistic regression adjusted for demographic and clinical characteristics. Subgroup analyses were conducted by age, risk group, and U.S. census region. Sensitivity analyses included inverse probability of treatment weighting (IPTW) and evaluation allowing previous PCV13 vaccination.
ResultsAmong 34,009 pneumonia hospitalizations, 837 (2.5%) were Streptococcus pneumoniae culture-positive and 7,428 (21.8%) individuals had received PCV20. PCV20 vaccination was associated with lower odds of culture-confirmed pneumococcal pneumonia hospitalization among adults aged [≥]65 years (VE 20.4%; 95% CI: 2.1%, 35.3%), with greater effectiveness observed among those with chronic medical conditions (VE 24.4%; 95% CI: 0.7%, 42.4%). VE was highest in the Western region among adults aged [≥]65 years (39.6%; 95% CI: 3.2%, 62.3%), a region with a high burden of serotype 4 disease. Overall, VE among adults aged [≥]18 years was 8.8% (95% CI: -8.8%, 23.6%). Findings were consistent across multivariable and IPTW-adjusted analyses.
ConclusionPCV20 provided significant protection against pneumococcal pneumonia hospitalizations among older adults, with greater effectiveness in regions where vaccine-covered serotypes are more prevalent. These findings support the importance of aligning pneumococcal vaccination strategies with regional serotype distribution to maximize vaccine impact.
Key SummaryThis study provides the first real-world evidence that PCV20 reduces culture-confirmed pneumococcal pneumonia hospitalizations among adults aged [≥]65 years, supporting the effectiveness of routine vaccination, with the greatest benefit observed in the Western U.S., where serotype 4 disease is predominant.
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BibTeX
@misc{ologunowa2026effectiveness,
title = {{Effectiveness of 20-valent pneumococcal conjugate vaccine against pneumococcal pneumonia hospitalizations among U.S. adults: Test-Negative Design}},
author = {A. J. Ologunowa and S. Kogut and V. L. Vrishali and S. A. Cohen and A. Caffrey},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.13.26362937},
url = {https://www.medrxiv.org/content/10.64898/2026.09.13.26362937v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Effectiveness of 20-valent pneumococcal conjugate vaccine against pneumococcal pneumonia hospitalizations among U.S. adults: Test-Negative Design
AU - A. J. Ologunowa
AU - S. Kogut
AU - V. L. Vrishali
AU - S. A. Cohen
AU - A. Caffrey
PY - 2026
DA - 2026/09/13
PB - medRxiv
DO - 10.64898/2026.09.13.26362937
UR - https://www.medrxiv.org/content/10.64898/2026.09.13.26362937v1
AB - ObjectiveThis study estimated the vaccine effectiveness (VE) of 20-valent pneumococcal conjugate vaccine (PCV20) against culture-confirmed pneumococcal pneumonia hospitalizations among adults using a test-negative case-control design. MethodsWe included adults ([≥]18 years) hospitalized with pneumonia in the U.S. Veterans Affairs Healthcare System between January 2023 and December 2025 who had respiratory cultures collected. VE was estimated using multivariable logistic regression adjusted for demographic and clinical characteristics. Subgroup analyses were conducted by age, risk group, and U.S. census region. Sensitivity analyses included inverse probability of treatment weighting (IPTW) and evaluation allowing previous PCV13 vaccination. ResultsAmong 34,009 pneumonia hospitalizations, 837 (2.5%) were Streptococcus pneumoniae culture-positive and 7,428 (21.8%) individuals had received PCV20. PCV20 vaccination was associated with lower odds of culture-confirmed pneumococcal pneumonia hospitalization among adults aged [≥]65 years (VE 20.4%; 95% CI: 2.1%, 35.3%), with greater effectiveness observed among those with chronic medical conditions (VE 24.4%; 95% CI: 0.7%, 42.4%). VE was highest in the Western region among adults aged [≥]65 years (39.6%; 95% CI: 3.2%, 62.3%), a region with a high burden of serotype 4 disease. Overall, VE among adults aged [≥]18 years was 8.8% (95% CI: -8.8%, 23.6%). Findings were consistent across multivariable and IPTW-adjusted analyses. ConclusionPCV20 provided significant protection against pneumococcal pneumonia hospitalizations among older adults, with greater effectiveness in regions where vaccine-covered serotypes are more prevalent. These findings support the importance of aligning pneumococcal vaccination strategies with regional serotype distribution to maximize vaccine impact. Key SummaryThis study provides the first real-world evidence that PCV20 reduces culture-confirmed pneumococcal pneumonia hospitalizations among adults aged [≥]65 years, supporting the effectiveness of routine vaccination, with the greatest benefit observed in the Western U.S., where serotype 4 disease is predominant.
ER -