Innate immunity in COVID-19
In many patients COVID-19 manifests as a flu-like disease. However, a small percentage of patients suffer severe organ complications, such as pneumonia or renal insufficiency. Recent evidence suggests that the innate immune system significantly contributes to this organ failure in COVID-19.
Plasma defence proteins known as complement and immune cells of the innate immune system, the neutrophils forming neutrophil extracellular traps (NETs), are strongly activated during SARS-CoV2 infection. The activation of these endogenous defence systems continues in the absence of the virus, inducing severe local and systemic inflammation. This “collateral damage” with local inflammation of the small vessels with subsequent thrombosis as well as the systemic inflammation play a crucial role in the development of organ failure in COVID-19.
The current project aims to identify complement and NET-forming neutrophils as the main drivers of local and systemic inflammation, resulting in thrombosis of small vessels with subsequent organ failure. Dissecting the activation pathways involved will enable us to design targeted therapies to inhibit complement activation and NET-forming neutrophils in order to prevent or alleviate organ failure due to the “collateral damage”.
Expected results and envisaged products
We will unravel the specific mechanism of complement and NET-forming neutrophil activation in COVID-19 and demonstrate their crucial role in the pathogenesis of inflammation and thrombosis of the small vessels. We will also demonstrate that the “collateral damage” caused by complement and NET-forming neutrophils is mainly responsible for organ failure.
Based on these results, we will be able to identify COVID-19 patients suitable for therapies specifically targeting complement and/or NET-forming neutrophils. Such an approach will inhibit inflammation, prevent organ failure and decrease the mortality rate.
Specific contribution to tackle the current pandemic
Only a minority of COVID-19 patients develop organ failure and require subsequent treatment on an intensive care unit. However, critically ill COVID-19 patients stay for a longer period in intensive care compared to other critically ill patients, placing a huge burden on infrastructure and ICU personnel. Prevention of organ failure by means of a targeted and timely intervention will decrease the percentage of COVID-19 patients admitted to intensive care and will contribute significantly to reducing the burden on the capacity of intensive care units.
Devils dance: complement, NETs and thrombosis in COVID-19