SARS-CoV-2 versus neutrophils: entrapped by neutrophil extracellular traps (NETs)

Abstract

Coronavirus disease COVID-19 is induced by SARS-CoV-2 virus leading to severe lung injury, but also other vital organs can be affected in its course. The infection can induce profound activation of the immune system, especially the innate response, leading to over-activation of leukocytes, including neutrophils. The latter cells are the most abundant type of white blood cells in humans, and they can release neutrophil extracellular traps (NETs) when strongly activated. NETs capture and immobilize pathogens such as bacteria and viruses, limiting their spread throughout the body. However, as they consist of cytotoxic proteins and nucleic acids which can also activate coagulation leading to thrombosis, also bystander host cells/organs can get injured. In the article we characterize NETs in terms of their structure, functions and side effects of their formation, but foremost we focus on up-to-date findings on NET involvement in COVID-19. NETs are strongly induced upon SARS-CoV-2 infection, and they cause numerous pathologies during COVID-19 which include multi-organ damage related to thrombosis. We also describe and discuss tested and potential therapies directed against NETs that can improve the condition of patients in the course of the disease and/or prevent mortality.