Neutrophil Extracellular Traps as Potential Driver of COVID-19 (Är neutrofiler involverade i sjukdomsutveckling av COVID-19?)

Neutrophils comprise the first line of defense against pathogens, as they are instrumental for killing the invaders by different means including NETosis (Neutrophil Extracellular Traps). Aberrant NET formation is linked to pathologies, such as organ damage and microthrombi formation. Approximately 5% of the COVID-19 patients require intensive care due to acute respiratory distress syndrome (ARDS), and patient stratification is of utmost importance in clinical decision-making. As severely sick ARDS and COVID-19 patients develop microthrombosis, we propose that the exacerbated host response triggers formation of intravascular NETs, resulting in microthrombi formation and consecutive multi-organ failure. WP1 investigates if circulating NETs can serve as a prognostic biomarker for disease progression using a unique method that we have developed on our collection of longitudinal blood samples from 200 COVID-19-patients at Danderyds hospital. Our preliminary data indicate a multifold increase of the circulating NET marker H3-Cit in COVID-19 patients, which will now be followed longitudinally and correlated with disease progression. Reducing NETs release might be attractive therapeutic strategies to revert COVID-19 development. To reveal how NETosis can be targeted, WP2 investigates which neutrophil subpopulation that release NETs in COVID19.  Preliminary data depict high expression of NET markers in neutrophils of COVID-19 patients, but few cells of the proangiogenic phenotype. Hematologi; Immunologi inom det medicinska området