The central role of neutrophil extracellular traps (NETs) and by-products in COVID-19 related pulmonary thrombosis

Extracellular trap networks (neutrophil extracellular traps [NETs]) of polymorphonuclear neutrophils are mesh-like substances that prevent the spread of pathogens. They primarily consist of DNA skeletons, histones, granule components, and cytoplasmic proteins. NETs formation requires a certain environment and there are different pathways for NETs production. However, it is still not clear how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes NETs. NETs exert antiinflammatory effects through immune response, while they can also lead to certain adverse outcomes, such as the development of immunothrombosis. Coronavirus disease 2019 (COVID-19) is an inflammatory reaction affecting various organs caused by SARS-CoV-2, especially the lungs. NETs production and disease severity are linked with unique neutrophil clusters by single-cell RNA sequencing. NETs might exert an anti-inflammatory role in the initial stage of lung tissue inflammation. Nevertheless, numerous studies and cases have shown that they can also result in pulmonary thrombosis. There is mounting evidence that NETs are tightly related with COVID-19 pulmonary thrombosis, and many studies on the mechanisms are involved. The role and mechanism of NETs in the development of pulmonary thrombosis will be the main topics of this manuscript. Additionally, we address the potential targeting of NETs in COVID-19 patients.