Background Paediatric pneumococcal conjugate vaccination (PCV) has reduced adult PCV-serotype disease: PCV7 has greater indirect effects than PCV13. Ongoing surveillance is required to evaluate current vaccine usage and inform future vaccine deployment, particularly with respiratory infection epidemiology changing following SARS-CoV-2 emergence.

Methods and Findings A retrospective cohort study, all adults ≥16 years admitted to three UK hospitals, 2006-2022, with pneumococcal disease. Medical records were reviewed for each clinical episode and serotype data were obtained from the UK Health Security Agency national reference laboratory.

We identified 1,501 (40.3%) cases of invasive pneumococcal disease (IPD) with known serotype, 134 (3.6%) IPD cases without serotype data, and 2,084 (56.0%) non-IPD cases, which are typically missed in national surveillance. Disease incidence increased progressively from 2006-2020, followed by a sudden decline after COVID-19 emergence and then a gradual increase to pre-pandemic levels.

Paediatric PCV7 introduction reduced adult PCV7 serotype IPD from 29.4% [24.1–35.4] of IPD in 2006-09 to 7.0% [3.7–12.7] in 2021-22. PCV13 introduction also decreased adult vaccine serotype IPD, but considerable residual adult disease remains, causing 34.3% [28.6–40.4] of IPD in 2006-09 and 21.7% [15.5–29.6] 9 in 2021-22, respectively. Serotype replacement diminished the benefits of PCV introduction: PCV20-13 and non-PCV serotypes represented 27.0% [21.9–32.9] and 9.3% [6.3–13.5] of disease in 2006-2009, and 39.5% [31.5–48.2] and 31.8% [24.4–40.2] in 2021-2022, respectively.

Serotype shifts have resulted in increasing disease caused by serotype 3 and 8, and the re-emergence of serotype 19F and 19A. These serotype shifts occurred as clinical disease severity changed, and whilst the COVID-19 pandemic disrupted disease severity trends, these have now largely reverted to previous trajectories. Patient age trended upwards and although CURB65 severity decreased there were increased ICU admission rates. Overall, inpatient mortality decreased and hospitalisation duration remained stable.

Conclusions After 17 years of PCV use, residual pneumococcal disease due to the vaccine serotypes among hospitalised adults remains. The sharp decline in pneumococcal disease during the COVID-19 pandemic has now reversed, with increasing cases due to vaccine serotypes, especially serotype 3. Around 68.2% of cases in 2022 were potentially covered by the recently licensed 20-valent PCV.

CH is Principal Investigator of the AvonCAP study which is an investigator-led University of Bristol study funded by Pfizer. AF is a member of the Joint Committee on Vaccination and Immunization (JCVI) and was, until December 2022, chair of the World Health Organization European Technical Advisory Group of Experts on Immunization (ETAGE) committee. In addition to receiving funding from Pfizer as Chief Investigator of this study, he leads another project investigating transmission of respiratory bacteria in families jointly funded by Pfizer and the Gates Foundation. The other authors have no relevant conflicts of interest to declare.

CH was funded by the National Institute for Health Research [NIHR Academic Clinical Fellowship (ACF-2015-25-002). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was approved by the Health Research Authority, UK (IRAS 265437).

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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Funding: CH was funded by the National Institute for Health Research [NIHR Academic Clinical Fellowship (ACF-2015-25-002). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Declarations: CH is Principal Investigator of the AvonCAP study which is an investigator-led University of Bristol study funded by Pfizer. AF is a member of the Joint Committee on Vaccination and Immunization (JCVI) and was, until December 2022, chair of the World Health Organization European Technical Advisory Group of Experts on Immunization (ETAGE) committee. In addition to receiving funding from Pfizer as Chief Investigator of this study, he leads another project investigating transmission of respiratory bacteria in families jointly funded by Pfizer and the Gates Foundation. The other authors have no relevant conflicts of interest to declare.

The data used in this study are sensitive and cannot be made publicly available without breaching patient confidentiality rules. Therefore, individual participant data and a data dictionary is not available to other researchers.