Proteomic profiling of end-stage COVID-19 lung biopsies

Clinical Proteomics

Research

Klaus Kratochwill¹  Florian Wiesenhofer¹  Laura Liesinger²  Martin Zacharias²  Juergen Gindlhuber²  Gregor Gorkiewicz²  Ruth Birner-Gruenberger³  Vadim Demichev⁴  Tamara Tomin⁵  Matthias Schittmayer⁵ 

[1] Christian Doppler Laboratory for Molecular Stress Research in Peritoneal Dialysis, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria;Division of Pediatric Nephrology and Gastroenterology, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria;Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria;Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria;Institute of Chemical Technologies and Analytics, Faculty of Technical Chemistry, Technische Universität Wien, Vienna, Austria;Institute of Biochemistry, Charité-Universitätsmedizin Berlin, Berlin, Germany;Institute of Chemical Technologies and Analytics, Faculty of Technical Chemistry, Technische Universität Wien, Vienna, Austria;

关键词: COVID-19;    SARS-CoV-2;    Lung;    Proteomics;    Extracellular matrix;    Signaling;   

DOI  :  10.1186/s12014-022-09386-6

 received in 2022-07-21, accepted in 2022-12-07,  发布年份 2022

来源: Springer

【 摘 要 】

The outbreak of a novel coronavirus (SARS-CoV-2) in 2019 led to a worldwide pandemic, which remains an integral part of our lives to this day. Coronavirus disease (COVID-19) is a flu like condition, often accompanied by high fever and respiratory distress. In some cases, conjointly with other co-morbidities, COVID-19 can become severe, leading to lung arrest and even death. Although well-known from a clinical standpoint, the mechanistic understanding of lethal COVID-19 is still rudimentary. Studying the pathology and changes on a molecular level associated with the resulting COVID-19 disease is impeded by the highly infectious nature of the virus and the concomitant sampling challenges. We were able to procure COVID-19 post-mortem lung tissue specimens by our collaboration with the BSL-3 laboratory of the Biobanking and BioMolecular resources Research Infrastructure Austria which we subjected to state-of-the-art quantitative proteomic analysis to better understand the pulmonary manifestations of lethal COVID-19. Lung tissue samples from age-matched non-COVID-19 patients who died within the same period were used as controls. Samples were subjected to parallel accumulation–serial fragmentation combined with data-independent acquisition (diaPASEF) on a timsTOF Pro and obtained raw data was processed using DIA-NN software. Here we report that terminal COVID-19 patients display an increase in inflammation, acute immune response and blood clot formation (with concomitant triggering of fibrinolysis). Furthermore, we describe that COVID-19 diseased lungs undergo severe extracellular matrix restructuring, which was corroborated on the histopathological level. However, although undergoing an injury, diseased lungs seem to have impaired proliferative and tissue repair signalling, with several key kinase-mediated signalling pathways being less active. This might provide a mechanistic link to post-acute sequelae of COVID-19 (PASC; “Long COVID”). Overall, we emphasize the importance of histopathological patient stratification when interpreting molecular COVID-19 data.

【 授权许可】

CC BY   
© The Author(s) 2022

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