Burden and Outcomes of Severe Lower Respiratory Tract Infections with Unknown Etiology: A Retrospective Observational Study on Epidemiological Trends Over an 8-Year Period (2016–2024)

Abstract Introduction Severe lower respiratory tract infections often require hospitalization, but a significant proportion lack microbiological diagnosis, leading to challenges in management. This study aimed to compare clinical outcomes of S-LRTIs with unknown versus known bacteria or viral etiolo...

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Main Authors: Giovanni Scaglione, Marta Canuti, Martina Offer, Valentina Breschi, Antonio Piralla, Fausto Baldanti, Gabriele Del Castillo, Francesco Scovenna, Sabrina Buoro, Federica Morani, Danilo Cereda, Alessandra Bandera, Andrea Gori, Marta Colaneri
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Language:English
Published: Adis, Springer Healthcare 2025-04-01
Series:Infectious Diseases and Therapy
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Online Access:https://doi.org/10.1007/s40121-025-01148-9
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author Giovanni Scaglione
Marta Canuti
Martina Offer
Valentina Breschi
Antonio Piralla
Fausto Baldanti
Gabriele Del Castillo
Francesco Scovenna
Sabrina Buoro
Federica Morani
Danilo Cereda
Alessandra Bandera
Andrea Gori
Marta Colaneri
author_facet Giovanni Scaglione
Marta Canuti
Martina Offer
Valentina Breschi
Antonio Piralla
Fausto Baldanti
Gabriele Del Castillo
Francesco Scovenna
Sabrina Buoro
Federica Morani
Danilo Cereda
Alessandra Bandera
Andrea Gori
Marta Colaneri
author_sort Giovanni Scaglione
collection DOAJ
description Abstract Introduction Severe lower respiratory tract infections often require hospitalization, but a significant proportion lack microbiological diagnosis, leading to challenges in management. This study aimed to compare clinical outcomes of S-LRTIs with unknown versus known bacteria or viral etiology in Lombardy, Italy. Methods A retrospective study analyzed respiratory infection-related hospitalizations in Lombardy over 8 years (2016–2024) using patient discharge charts. Patients were categorized into four groups: bacterial, viral (non-COVID-19), COVID-19-related, and unknown etiology. Outcomes included length of stay, intensive care unit admissions, and intra-hospital mortality. Temporal, seasonal, and age-specific trends were evaluated. Results Among 683,741 hospitalizations, 338,211 (49.5%) were of unknown etiology, showing a 12.3% intra-hospital mortality rate (41,627 deaths) and 4.0% intensive care unit admission rate (13,625 admissions). COVID-19-related hospitalizations had the highest intra-hospital mortality rate (22.0%, 36,446 deaths in 165,605 COVID-19-related hospitalizations) and number of intensive care unit admissions (14,725 admissions, 8.9% of COVID-19-related hospitalizations), while viral non-COVID-19 hospitalizations showed the lowest intra-hospital mortality rate (3.2%, 1114 deaths in 34,769 viral-non-COVID-19 hospitalizations) and shortest length of stay (11.9 days). Hospitalizations with unknown etiology were more common in minors (42,190 episodes, 57.6% of total in < 18 years) and elderly (358,534 episodes, 56.2% of total in > 75 years), especially during warm seasons. Post-pandemic years saw increased bacterial and viral hospitalizations alongside a reduced proportion of those without an unknown etiology. Conclusions Respiratory infection-related hospitalizations with unknown etiology are associated with distinct seasonal and demographic patterns, and poorer outcomes compared to viral non-COVID-19 hospitalizations. COVID-19 reshaped S-LRTI epidemiology and diagnostic approaches, highlighting the need for comprehensive pathogen panels and tailored management strategies, while promoting their expanded use. Future research should integrate detailed clinical data to improve understanding and outcomes of severe respiratory infections, especially in vulnerable populations.
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spelling doaj-art-9e0169f27c3444e996cefdc1e9b115a02025-08-20T03:53:46ZengAdis, Springer HealthcareInfectious Diseases and Therapy2193-82292193-63822025-04-011451075108710.1007/s40121-025-01148-9Burden and Outcomes of Severe Lower Respiratory Tract Infections with Unknown Etiology: A Retrospective Observational Study on Epidemiological Trends Over an 8-Year Period (2016–2024)Giovanni Scaglione0Marta Canuti1Martina Offer2Valentina Breschi3Antonio Piralla4Fausto Baldanti5Gabriele Del Castillo6Francesco Scovenna7Sabrina Buoro8Federica Morani9Danilo Cereda10Alessandra Bandera11Andrea Gori12Marta Colaneri13Department of Infectious Diseases, Luigi Sacco Hospital, University of MilanDepartment of Veterinary and Animal Sciences, University of CopenhagenDepartment of Biomedical and Clinical Sciences, University of MilanDepartment of Electrical Engineering, Eindhoven University of TechnologyMicrobiology and Virology Department, Fondazione IRCCS Policlinico San MatteoMicrobiology and Virology Department, Fondazione IRCCS Policlinico San MatteoPrevention Unit, General Directorate of HealthDepartment of Health Sciences, University of MilanClinical Chemistry Laboratory, Hospital Papa Giovanni XXIIIDepartment of Biology, University of PisaPrevention Unit, General Directorate of HealthDepartment of Pathophysiology and Transplantation, University of MilanoDepartment of Infectious Diseases, Luigi Sacco Hospital, University of MilanDepartment of Infectious Diseases, Luigi Sacco Hospital, University of MilanAbstract Introduction Severe lower respiratory tract infections often require hospitalization, but a significant proportion lack microbiological diagnosis, leading to challenges in management. This study aimed to compare clinical outcomes of S-LRTIs with unknown versus known bacteria or viral etiology in Lombardy, Italy. Methods A retrospective study analyzed respiratory infection-related hospitalizations in Lombardy over 8 years (2016–2024) using patient discharge charts. Patients were categorized into four groups: bacterial, viral (non-COVID-19), COVID-19-related, and unknown etiology. Outcomes included length of stay, intensive care unit admissions, and intra-hospital mortality. Temporal, seasonal, and age-specific trends were evaluated. Results Among 683,741 hospitalizations, 338,211 (49.5%) were of unknown etiology, showing a 12.3% intra-hospital mortality rate (41,627 deaths) and 4.0% intensive care unit admission rate (13,625 admissions). COVID-19-related hospitalizations had the highest intra-hospital mortality rate (22.0%, 36,446 deaths in 165,605 COVID-19-related hospitalizations) and number of intensive care unit admissions (14,725 admissions, 8.9% of COVID-19-related hospitalizations), while viral non-COVID-19 hospitalizations showed the lowest intra-hospital mortality rate (3.2%, 1114 deaths in 34,769 viral-non-COVID-19 hospitalizations) and shortest length of stay (11.9 days). Hospitalizations with unknown etiology were more common in minors (42,190 episodes, 57.6% of total in < 18 years) and elderly (358,534 episodes, 56.2% of total in > 75 years), especially during warm seasons. Post-pandemic years saw increased bacterial and viral hospitalizations alongside a reduced proportion of those without an unknown etiology. Conclusions Respiratory infection-related hospitalizations with unknown etiology are associated with distinct seasonal and demographic patterns, and poorer outcomes compared to viral non-COVID-19 hospitalizations. COVID-19 reshaped S-LRTI epidemiology and diagnostic approaches, highlighting the need for comprehensive pathogen panels and tailored management strategies, while promoting their expanded use. Future research should integrate detailed clinical data to improve understanding and outcomes of severe respiratory infections, especially in vulnerable populations.https://doi.org/10.1007/s40121-025-01148-9Lower respiratory tract infectionsEpidemiologySurveillanceUnknown etiologyCOVID-19
spellingShingle Giovanni Scaglione
Marta Canuti
Martina Offer
Valentina Breschi
Antonio Piralla
Fausto Baldanti
Gabriele Del Castillo
Francesco Scovenna
Sabrina Buoro
Federica Morani
Danilo Cereda
Alessandra Bandera
Andrea Gori
Marta Colaneri
Burden and Outcomes of Severe Lower Respiratory Tract Infections with Unknown Etiology: A Retrospective Observational Study on Epidemiological Trends Over an 8-Year Period (2016–2024)
Infectious Diseases and Therapy
Lower respiratory tract infections
Epidemiology
Surveillance
Unknown etiology
COVID-19
title Burden and Outcomes of Severe Lower Respiratory Tract Infections with Unknown Etiology: A Retrospective Observational Study on Epidemiological Trends Over an 8-Year Period (2016–2024)
title_full Burden and Outcomes of Severe Lower Respiratory Tract Infections with Unknown Etiology: A Retrospective Observational Study on Epidemiological Trends Over an 8-Year Period (2016–2024)
title_fullStr Burden and Outcomes of Severe Lower Respiratory Tract Infections with Unknown Etiology: A Retrospective Observational Study on Epidemiological Trends Over an 8-Year Period (2016–2024)
title_full_unstemmed Burden and Outcomes of Severe Lower Respiratory Tract Infections with Unknown Etiology: A Retrospective Observational Study on Epidemiological Trends Over an 8-Year Period (2016–2024)
title_short Burden and Outcomes of Severe Lower Respiratory Tract Infections with Unknown Etiology: A Retrospective Observational Study on Epidemiological Trends Over an 8-Year Period (2016–2024)
title_sort burden and outcomes of severe lower respiratory tract infections with unknown etiology a retrospective observational study on epidemiological trends over an 8 year period 2016 2024
topic Lower respiratory tract infections
Epidemiology
Surveillance
Unknown etiology
COVID-19
url https://doi.org/10.1007/s40121-025-01148-9
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