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.
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