Abstract
The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has resulted in a pandemic with over 270 million confirmed cases and 5.3 million deaths worldwide. In some cases, the infection leads to acute respiratory distress syndrome (ARDS), which is triggered by a cytokine storm and multiple organ failure. Clinical hematological, biochemical, coagulation, and inflammatory markers, such as interleukins, are associated with COVID-19 disease progression. In this regard, neutrophilia, neutrophil-to-lymphocyte ratio (NLR), and neutrophil-to-albumin ratio (NAR), have emerged as promising biomarkers of disease severity and progression. In the pathophysiology of ARDS, the inflammatory environment induces neutrophil influx and activation in the lungs, promoting the release of cytokines, proteases, reactive oxygen species (ROS), and, eventually, neutrophil extracellular traps (NETs). NETs components, such as DNA, histones, myeloperoxidase, and elastase, may exert cytotoxic activity and alveolar damage. Thus, NETs have also been described as potential biomarkers of COVID-19 prognosis. Several studies have demonstrated that NETs are induced in COVID-19 patients, and that the highest levels of NETs are found in critical ones, therefore highlighting a correlation between NETs and severity of the disease. Knowledge of NETs signaling pathways, and the targeting of points of NETs release, could help to develop an effective treatment for COVID-19, and specifically for severe cases, which would help to manage the pandemic.
Highlights
The infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)was designated by the World Health Organization as coronavirus disease 2019 (COVID-19)when it emerged in 2019 in Wuhan (China) [1]
Reports suggest that the S1 subunit is responsible for binding to the human angiotensin-converting enzyme II (ACE2), a metallopeptidase that mediates the process of virus entry [5,6] into the host cells by endocytosis, while the S2 subunit is responsible for the fusion of the membranes of the virus with those of the host cells [3]
Current research is focused on circulating active neutrophils as the source, of the release of cytokines, and of the formation of neutrophil extracellular traps (NETs) involved in lung tissue damage (Figure 1), which have been detected in SARS-CoV-2-infected patients
Summary
The infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The present study reviews the latest clinical studies of the initial biomarkers associated with fatal COVID-19 progression It focuses on the source of immune cells and the signaling pathways of the inflammatory and biochemical mediators involved in multiorgan failure, with the intention of identifying new therapeutic targets to prevent the progression of the illness. In order to identify (in ClinicalTrials) the drugs related to NETs that are currently the subject of a clinical trial, we employed the following key words in the search field “condition or disease”: COVID, SARS-CoV-2, Coronavirus disease 2019, Severe Acute Respiratory. We filtered the results by introducing the following drug names in the “interventions” column: colchicine, disulfiram, metformin, alvelestat, fostamatinib, Vitamin D, Vitamin D3, 25-Hydroxivitamin D3, cholecalciferol, Nacetylcysteine, dornase alfa, pulmozyme These search terms rendered a total of 92 results, on which we have based the present study
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