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2023
Journal Article
Titel
Proteomics reveals antiviral host response and NETosis during acute COVID-19 in high-risk patients
Abstract
SARS-CoV-2 remains an acute threat to human health, endangering hospital capacities worldwide. Previous studies have aimed at informing pathophysiologic understanding and identification of disease indicators for risk assessment, monitoring, and therapeutic guidance. While findings start to emerge in the general population, observations in high-risk patients with complex pre-existing conditions are limited.We addressed the gap of existing knowledge with regard to a differentiated understanding of disease dynamics in SARS-CoV-2 infection while specifically considering disease stage and severity. We biomedically characterized quantitative proteomics in a hospitalized cohort of COVID-19 patients with mild to severe symptoms suffering from different (co)-morbidities in comparison to both healthy individuals and patients with non-COVID related inflammation. Deep clinical phenotyping enabled the identification of individual disease trajectories in COVID-19 patients. By the use of the individualized disease phase assignment, proteome analysis revealed a severity dependent general type-2-centered host response side-by-side with a disease specific antiviral immune reaction in early disease. The identification of phenomena such as neutrophil extracellular trap (NET) formation and a pro-coagulatory response characterizing severe disease was successfully validated in a second cohort. Together with the regulation of proteins related to SARS-CoV-2-specific symptoms identified by proteome screening, we not only confirmed results from previous studies but provide novel information for biomarker and therapy development.
Author(s)
Hellmuth, Johannes C.
Ludwig-Maximilians-Universität München, University Hospital, Department of Medicine III
Kneidinger, Nikolaus
Helmholtz Zentrum Muenchen, Institute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive
Motaharehsadat, Heydarian
Ludwig-Maximilians-Universität München, University Hospital, COVID-19 Registry of the LMU Munich (CORKUM)
Frankenberger, Marion
Ludwig-Maximilians-Universität München, University Hospital, COVID-19 Registry of the LMU Munich (CORKUM)
Stubbe, Hans C.
Ludwig-Maximilians-Universität München, University Hospital, COVID-19 Registry of the LMU Munich (CORKUM)
Ryffel, Bernhard
CNRS-University of Orleans and Artimmune, UMR 7355, Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM)
Behr, Jürgen
Helmholtz Zentrum Muenchen, Institute of Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive
Kaiser, Rainer
Ludwig-Maximilians-Universität München, University Hospital, COVID-19 Registry of the LMU Munich (CORKUM)
Scherer, Clemens
Ludwig-Maximilians-Universität München, University Hospital, COVID-19 Registry of the LMU Munich (CORKUM)
Teupser, Daniel
Ludwig-Maximilians-Universität München, University Hospital, Institute of Laboratory Medicine
Muenchhoff, Maximilian
Ludwig-Maximilians-Universität München, University Hospital, COVID-19 Registry of the LMU Munich (CORKUM)
Funder
Bayerisches Staatsministerium für Wirtschaft, Landesentwicklung und Energie
Verbund
Fraunhofer-Verbund IUK-Technologie