Respiratory infections pose significant challenges to global health, impacting millions of individuals annually. Understanding the molecular mechanisms underlying the pathogenicity of these infections is crucial for developing effective interventions. RNA sequencing provides insights into a patient's global transcriptome changes, facilitating the identification of host gene signatures in response to infection and potential therapeutic targets. Here we present an extensive whole blood transcriptome dataset from a demographically diverse cohort of 502 patients with infections including COVID-19, seasonal coronavirus, influenza A or influenza B, sepsis, septic shock, and co-infections (Viral/Viral, Bacterial/Viral, Bacterial/Viral/Fungal, Viral/Fungal, Viral/ Viral/Fungal). The cohort size and depth of data showcase its potential to unravel respiratory infection pathogenesis for the development of better diagnostics, treatments, and preventive strategies for respiratory infections and future global health crises.

Centenary Institute University of Sydney Sydney NSW Australia

Centre for Clinical Research in Emergency Medicine Harry Perkins Institute of Medical Research Royal Perth Hospital University of Western Australia Perth WA Australia

Centre for Immunology and Allergy Research The Westmead Institute for Medical Research The University of Sydney Westmead NSW Australia

Centre for Infectious Diseases and Microbiology The Westmead Institute for Medical Research Westmead NSW Australia

Centre for Virology Research the Westmead Institute for Medical Research Westmead NSW Australia

Computational Sciences Department The Jackson Laboratory Farmington CT USA

Department of Clinical Immunology Royal Prince Alfred Hospital Camperdown NSW Australia

Department of Infectious Diseases and Microbiology the Children's Hospital at Westmead Westmead NSW Australia

Department of Infectious Diseases and Microbiology Westmead Hospital WSLHD Westmead NSW Australia

Department of Infectious Diseases The University of Melbourne at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia

Department of Intensive Care Medicine Amiens University Hospital Amiens France

Department of Intensive Care Medicine Nepean Hospital Penrith NSW Australia

Department of Microbiology Immunology and Biochemistry University of Tennessee Health Science Centre Memphis Tennessee USA

Department of Surgery Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore

Emergency Medicine Department National University Hospital Singapore Singapore

Faculty of Medicine and Health School of Medical Sciences The University of Sydney Sydney NSW Australia

Faculty of Medicine and Health Sydney Medical School Nepean Nepean Hospital University of Sydney Sydney NSW Australia

Faculty of Medicine and Health Sydney Medical School Westmead Westmead Hospital University of Sydney Westmead NSW Australia

Faculty of Medicine Universitas Tarumanagara Jakarta Indonesia

Institute of Virology Münster University of Münster Münster Germany

Medical ICU 1st Department of Internal Medicine Charles University and Teaching Hospital Pilsen 323 00 Plzeň Czech Republic

Medistra Hospital Gatot Subroto Kav 59 Jakarta Indonesia

Research and Education Network Western Sydney Local Health District Westmead Hospital Westmead NSW Australia

RPA Virtual Hospital Sydney Local Health District Camperdown NSW Australia

School of Chemistry and Molecular Biosciences The University of Queensland Brisbane QLD Australia

St Jude Children's Research Hospital Memphis TN USA

Sydney ID Sydney Medical School University of Sydney Sydney NSW Australia

Sydney Informatics Hub Core Research Facilities University of Sydney Sydney NSW Australia

Sydney Institute for Infectious Disease The University of Sydney Sydney NSW Australia

Translational Medicine Division Research Branch Sidra Medicine Doha Qatar

Victorian Infectious Disease Service The Royal Melbourne Hospital Melbourne VIC Australia

Westmead Hospital Western Sydney Local Health District Westmead NSW Australia

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