Lung protection in severe COVID-19 by means of Tie2 agonism (C06)

• Subject Area: Pneumology, Thoracic Surgery
• Term: from 2010 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 114933180

COVID-19 causes failure of the alveolo-capillary barrier, a characteristic for life-threatening ARDS. The Ang/Tie2 pathway was shown to be centrally involved in the regulation of lung barrier function in pneumonia. Therefore, we will specifically (1) quantify Ang-2 levels in serum of hospitalised COVID-19 patients and analyse its prognostic/predictive value regarding COVID-19 trajectories and outcome, as compared to CAP of other origin; (2) evaluate the protective effect of Tie2 agonism on endothelial permeability in vitro induced by serum of COVID-19 patients, and (3) study different barrier stabilizing interventions targeting Tie2 signaling in hamster models of SARS-CoV-2 infection. The data collected in these experiments are expected to establish the Ang/Tie2 system as a critical regulator of lung barrier integrity in COVID-19, and will provide a rationale for risk stratification in COVID-19 and treatment of COVID-19 associated ARDS based on the Ang/Tie2 system.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 84: Innate Immunity of the Lung: Mechanisms of Pathogen Attack and Host Defence in Pneumonia
• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Project Heads: Professor Dr. Norbert Weißmann; Professor Dr. Martin Witzenrath