Streptococcus pneumoniae re-emerges as a cause of community-acquired pneumonia, including frequent co-infection with SARS-CoV-2, in Germany, 2021

Background The COVID-19 pandemic and the associated containment measures had a substantial impact on pathogens causing pneumonia in adults. The objective of this study was to determine the etiology of hospitalized community-acquired pneumonia (CAP) among adults in Germany in 2021, the second year of the COVID-19 pandemic. Methods Since January 2021, this on-going, prospective, population-based surveillances study enrolled adult patients with clinically and radiographically confirmed CAP at three hospitals in Thuringia, Germany, serving a population of approximately 280,000. Urine samples were collected from patients and tested for S. pneumoniae using the pneumococcal urinary antigen test (PUAT, BinaxNOW S. pneumoniae ) and the proprietary serotype-specific urinary antigen detection (UAD) assays. Nasopharyngeal swabs were tested for 10 respiratory viruses by PCR. Results A total of 797 patients were enrolled, of whom 760 were included in the analysis. The median age of patients with CAP was 67 years; in-hospital case-fatality rate was 8.4%. A respiratory pathogen was detected in 553 (72.8%) patients. The most common pathogen was SARS-CoV-2 (n=498, 68.2%), followed by S. pneumoniae (n=40, 6.4%). Serotypes contained in the 13-valent, 15-valent and 20-valent pneumococcal conjugate vaccine were detected in 42.5%, 45.0%, and 70.0% of the pneumococcal CAP cases. Between the first and second half of 2021, the proportion of CAP cases associated with S. pneumoniae increased from 1.1% to 5.6% in patients aged 18-59 years and from 2.5% to 12.4% in those aged ≥60 years; coinfection of SARS-CoV-2 and S. pneumoniae among COVID-19 patients increased from 0.7% (2/283 cases) to 6.0% (13/215) in patients aged ≥18 years, and from 1.0% (2/195) to 8.7% (11/127) in those aged ≥60 years. Conclusion In Germany, the proportion of CAP cases associated with S. pneumoniae rebounded to a near-pandemic level in the second half of 2021 and many pneumococcal infections occurred in patients with COVID-19. Vaccination uptake against respiratory pathogens, including S. pneumoniae , should be strengthened. ### Competing Interest Statement C.T., K.P., L.W., C.S., C.v.E. and B.D.G. are full time employees of Pfizer Vaccines and hold stock and/or stock options. M.W.P. reports research support and personal fees from Merck Sharp & Dohme LLC and Pfizer Inc and personal fees from Sanofi. S.H. reports payments or honoraria from Pfizer Inc, Infectopharm, Philips, Advanz, Shionogi, Tillots, ThermoFisher and support for attending meetings and travel by Pfizer, Infectopharm, Philips, Advanz, Shionogi, Tillots. J.A. has no declarations. ### Funding Statement This study was funded by Pfizer Inc. ### Author Declarations 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: Ethics Committee of the Friedrich-Schiller University Jena at the medical faculty gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes 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). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.