Mechanistic and therapeutic studies of the innate immune response in human subjects with COVID-19 (Mekanistiska och terapeutiska studier av det mänskliga medfödda immunsvaret vid COVID-19)

The aim of this application is to find evidence for that the humoral innate immune system (HIIS) involving at least the contact-, complement-, coagulation- and the fibrinolytic- systems are activated in COVID-19. Our hypothesis is that activation of HIIS by virus directly or more likely by large amounts of activated and damaged (apoptotic and necrotic) cells, is the pathophysiological mechanism of the respiratory distress syndrome (RDS) linked to COVID-19. The rationale for this is to find the mechanism of the RDS associated with COVID-19, to identify new targets for therapeutic intervention and to obtain support for giving already licensed therapeutic inhibitors of these systems to patients with COVID-19 RDS.The preliminary data suggest that the cascade systems of the blood are engaged in a thromboinflammatory reaction caused by the virus or infected cells and seems to be a prognostic factor that can be used immediately in the clinic. If we together with our colleagues in Milan and Philadelphia can show that complement inhibition with AMY-101 is beneficial for the patients, a new treatment for COVID-19 patients can be developed. Also, other already licensed therapeutics e.g. in the contact system, are available and can if the mechanism is clarified, be used in future clinical trials for treatment of COVID-19 patients. Klinisk laboratoriemedicin