The central role of neutrophil extracellular traps in SARS-CoV-2-induced thrombogenesis and vasculitis

Objective: Severe acute lung injury (ALI) and acute respiratory
distress syndrome (ARDS) seen in SARs-CoV-2 infection
has been attributed to the disruption of the immune response
in COVID-19 patients. Neutrophilia and marked lymphocyte
reductions are associated with disease severity and seem predictive
of disease outcome in moderate and severe COVID-19
patients. Herein, we aim to decipher possible mechanisms
involved in extensive tissue injury observed in COVID-19
patients, accompanied by vasculopathy, coagulopathy, and
a high incidence of thrombotic complications in severe patients.
Methods: We searched PubMED for keywords including
COVID-19 pathogenesis, thrombosis, and vasculities.
Results: Neutrophils can undergo a specialized form of
apoptosis to yield thread-like extracellular structures termed
neutrophil extracellular traps (NETs), termed NETosis,
which form web-like scaffolds of DNA, histones, and toxic
protein granules and enzymes, whose primary function is
to trap and eliminate microbes. However, uncontrolled NET
production can lead to ALI and ARDS, coagulopathy, multiple
organ failure, and autoimmune disease. Dysregulation
of NETs promotes production of anti-neutrophil cytoplasmic
antibodies (ANCA) which affects small vessels through ANCA-
associated vasculitis (AAV). Furthermore, NETs can also
induce thrombosis via formation of scaffolds that trap platelets,
RBCs, fibronectin, and other proteins, which can also induce
coagulation.
Conclusion: We suggest that NET production is central
during SARS-CoV-2 infection and COVID-19 pathogenesis,
associated with alveolar damage accumulation of edema, endothelial
injury and coagulopathy, elevated platelet activation
and thrombogenesis forming a NET production feed-for-pathogeneward
loop, causing diffuse small vessel vasculitis in the lungs
and other organs.

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