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Bauer, A. ; Pachl, E. ; Hellmuth, J.C.* ; Kneidinger, N. ; Heydarian, M.* ; Frankenberger, M.* ; Stubbe, H.C.* ; Ryffel, B.* ; Petrera, A. ; Hauck, S.M. ; Behr, J.* ; Kaiser, R.* ; Scherer, C.* ; Deng, L. ; Teupser, D.* ; Ahmidi, N.* ; Muenchhoff, M.* ; Schubert, B. ; Hilgendorff, A.

Proteomics reveals antiviral host response and NETosis during acute COVID-19 in high-risk patients.

Biochim. Biophys. Acta-Mol. Basis Dis. 1869:166592 (2022)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Biomarker ; Covid-19 ; High-risk Patients ; Immune Response ; Netosis ; Proteomics; Thrombosis; Package
Language english
Publication Year 2022
HGF-reported in Year 2022
ISSN (print) / ISBN 0925-4439
e-ISSN 1878-2434
Journal Biochimica et Biophysica Acta - Molecular Basis of Disease
Quellenangaben Volume: 1869, Issue: 2, Pages: , Article Number: 166592 Supplement: ,
Publisher Elsevier
Publishing Place Radarweg 29, 1043 Nx Amsterdam, Netherlands
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)
Institute of Computational Biology (ICB)
CF Metabolomics & Proteomics (CF-MPC)
Institute of Virology (VIRO)
POF-Topic(s) 30202 - Environmental Health
30205 - Bioengineering and Digital Health
30203 - Molecular Targets and Therapies
Research field(s) Lung Research
Enabling and Novel Technologies
Immune Response and Infection
PSP Element(s) G-552100-001
G-503800-001
G-503800-007
G-501600-001
G-505700-001
G-554300-001
Grants
Helmholtz Association's Initiative and Networking Fund through Helmholtz AI
Stiftung AtemWeg (LSS AIRR)
Research Training Group Targets in Toxicology of the German Science and Research Organization (DFG)
German Center for Lung Research (DZL, German Ministry of Education and Health (BMBF))
Bavarian Ministry for Economic Affairs, Regional Development and Energy
Free State of Bavaria under the Excellence Strategy of the Federal and State Government (LMUexcellent)
Free State of Bavaria under the Excellence Strategy of the Federal and State Government (LMUexcellent) - Bavarian Ministry for Economic Affairs, Regional Development and Energy as part of a project
COMBAT C19IR
DOI 10.1016/j.bbadis.2022.166592
WOS ID 000894174700002
WOS ID WOS:000894174700002
PubMed ID 36328146
Erfassungsdatum 2022-12-05
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