P140 Lupuzor covid 1925 May 2020 22:06
Neutrophilia and NETopathy as Key Pathologic Drivers of Progressive Lung
Impairment in Patients with COVID-19
Teluguakula Narasaraju1,
Chow5 and Marko Radic6*.
Benjamin M. Tang2, Martin Herrmann3, Sylviane Muller4, Vincent TK
1College of Veterinary Medicine, Oklahoma State University, Stillwater, Oklahoma USA.
2Department of Intensive Care Medicine, Nepean Hospital, Sydney, Australia.
3Department of Internal Medicine 3, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
4CNRS-University of Strasbourg, Biotechnology and Cell Signaling, Illkirch, France/Laboratory of Excellence Medalis, Institut de science et d’ingénierie supramoléculaire, and University of Strasbourg Institute for Advanced Study (USIAS), 67000 Strasbourg, France.
5Department of Microbiology and Immunology, School of Medicine, National University of Singapore, National University Health System, Singapore.
6Department of Microbiology, Immunology and Biochemistry, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
Targeting neutrophils and NETs-associated lung injury in patients with severe COVID-19.
Administration of drugs that prevent neutrophil recruitment and activity may effectively attenuate the pathologic complications of alveolitis and vascular injury in patients with COVID-19, and initial results of several treatment strategies have been reported.8 One early randomized clinical trial was the infusion of vitamin C in patients with COVID-19, based on the hypothesis that vitamin C suppresses neutrophil influx, activation, and NET-associated alveolar-capillary damage.41 Although vitamin C exhibits anti-oxidant function, its effect on reducing neutrophil activity and NETs-mediated pathologies in vivo may be limited. In contrast, small molecules and peptides may reduce NET release in important ways. This is the case of peptide P140, which prevents NET release in vitro42. This peptide regulates chaperone- mediated autophagy and macroautophagy, thereby reducing excessive inflammation in animal models and autoimmune patients. The effect of P140 on the neutrophil influx in the bronchoalveolar space requires further attention.