The role of the formation of neutrophil extracellular traps (NETosis) in the pathophysiology and the complications of COVID-19
Authors: Sharma Vagisha , Aden Durre , Zaheer Sufian , Ranga Sunil 
Published: August 2023

Coronavirus disease 2019 (COVID-19) pandemic which caused a significant disaster globally, has long term health implication known as long COVID. Long COVID refers to a wide range of symptoms that persist or develop after the acute phase of COVID-19 infection, which can last for weeks or months. Some of the symptoms associated with long COVID include fatigue, shortness of breath, chest pain, joint pain, cognitive impairment, and depression. Recent studies have also shown that long COVID can lead to various cardiovascular complications, including myocarditis, pericarditis, heart failure, and arrhythmias. These can significantly increase morbidity and mortality rates in COVID-19 patients, particularly those with preexisting cardiovascular conditions. The exact mechanisms underlying the cardiovascular complications associated with long COVID are not yet fully understood. However, it is believed that the persistent inflammation and immune dysregulation associated with COVID-19 may contribute to endothelial dysfunction, oxidative stress, and fibrosis in the cardiovascular system, leading to long-term cardiovascular complications. Neutrophils play a crucial role in immune system's response to infection. Upon encountering pathogens, neutrophils release neutrophil extracellular traps (NETs) to trap and kill microbes. The severity of COVID-19 has been linked to various factors, including the role of neutrophils and NETs. These extracellular webs, composed of chromatin, microbicidal proteins, and oxidant enzymes, are released by neutrophils to fight infections. However, excessive or dysregulated NET formation can lead to damage to surrounding tissues and organs, contributing to the development of inflammatory and thrombotic complications in various diseases, including COVID-19. COVID-19 patients with severe disease have increased levels of NETs in their blood, suggesting that NETs contribute to the disease's pathogenesis. NETs have been implicated in COVID-19-associated coagulopathy, acute respiratory distress syndrome, and multi-organ failure. Moreover, the presence of autoantibodies that target NET components has been reported in COVID-19 patients with severe disease, indicating that these autoantibodies may contribute to the development of hyperinflammation and thrombosis. Several potential therapeutic interventions targeting NETs have been proposed for COVID-19 patients, including the use of agents that inhibit NET formation or degradation. The role of NETs in the pathogenesis of COVID-19 and its associated complications is an active area of research. Further studies are needed to elucidate the mechanisms underlying NET dysregulation in COVID-19 and to evaluate the potential of NET-targeting therapies as a treatment strategy for COVID-19 patients. The purpose of this review is to analyze the potential contribution of NETosis in the pathophysiology of COVID-19 and its subsequent complications apart from its beneficial effect. This may provide insight into potential therapeutic interventions for COVID-19 patients.