Abstract
Despite ongoing vaccination COVID-19 is a global healthcare problem because of the lack of an effective targeted therapy. In severe COVID-19 manifesting as acute respiratory distress syndrome, uncontrolled innate immune system activation results in cytokine deregulation, damage-associated molecular patterns release upon tissue damage and high occurrence of thrombotic events. These pathomechanisms are linked to neutrophil function and dysfunction, particularly increased formation of neutrophil extracellular traps (NETs). While the association of NETs and severity of COVID-19 has been shown and proved, the causes of NETs formation are unclear. The aim of this review is to summarize potential inducers of NETs formation in severe COVID-19 and to discuss potential treatment options targeting NETs formation of removal.
Highlights
SARS-CoV-2 causes much more than just COVID-19
Several studies found that the production of neutrophil extracellular traps (NETs) is increased in COVID-19 and their concentration is associated with severity of the disease and thrombosis [96–100], and NETs were found to be predominantly located in the lower respiratory tract of critically-ill patients [101]
Skendros and his colleagues even proposed a mechanism of NETs induced thrombosis in COVID-19, where SARS-CoV-2 triggered complement activation leads to thrombin induced expression of tissue factor (TF) in neutrophils, which results in TF rich procoagulatory NETs [100]
Summary
SARS-CoV-2 causes much more than just COVID-19. The world is still facing huge socio-economic problems that will likely persist much longer than the pandemic itself [1]. If not enough people are vaccinated, the pandemic will not stop [7] If such a scenario occurs, the only remaining solution will be targeted and effective treatment of patients with severe COVID-19 [8]. The damaged endothelium facilitates coagulation and thrombus formation, whether in large vessels or in small arterioles and capillaries [21] This thrombosis and subsequent coagulopathy cannot, be resolved by artificial lung ventilation and additional oxygenation [22]. Thrombotic complications were found to be one of the major issues in treating critically ill ICU patients with COVID-19 [23]. It has become clear, that identifying the initiators and drivers of thrombosis is vital
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