ABSTRACT
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. Method(s): We searched PubMED for keywords including COVID-19 pathogenesis, thrombosis, and vasculities. Result(s): 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(s): 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-forward loop, causing diffuse small vessel vasculitis in the lungs and other organs. Copyright © 2020 FSG Communications Ltd. All rights reserved.
ABSTRACT
Some coronavirus disease-2019 (COVID-19) patients exhibit multi-organ failure, which often includes the liver. Indeed, liver disease appears to be an emerging feature of COVID-19 infections. However, the exact mechanism behind this remains unknown. Neutrophil extracellular traps (NETs) have increasingly been attributed as major contributors to various liver pathologies, including sepsis, ischemic-reperfusion (I/R) injury, and portal hypertension in the setting of chronic liver disease. Although vital in normal immunity, excessive NET formation can drive inflammation, particularly of the endothelium. Collectively, we propose that NETs observed to be elevated in severe COVID-19 infection play principal roles in liver injury in addition to acute lung injury. Herein, we discuss the potential mechanisms underlying COVID-induced liver injury including cytopathic effects from direct liver infection, systemic inflammatory response syndrome, and hypoxic injury, encompassing I/R injury and coagulopathy. Further research is required to further elucidate the role of NETs in COVID. This holds potential therapeutic significance, as inhibition of NETosis could alleviate the symptoms of acute respiratory distress syndrome and liver injury, as well as other organs.
ABSTRACT
Less than 2% of children are reported to test positive for SARS-CoV-2. However, increasing reports have described COVID-positive children demonstrating symptoms like Kawasaki disease (KD), an acute vasculitis in medium sized vessels. Characteristic clinical features of KD include fever, conjunctivitis, mucosal alterations, rashes, and cervical lymphadenopathy. We searched PubMed with six keywords including neutrophil and macrophage extracellular traps (NETs/METs), Kawasaki disease, vasculitis, COVID-19 and SARS-CoV-2. We discussed here how SARS-CoV-2 infection is accompanied by activation of proinflammatory cytokines, specifically IL-1 beta and production of neutrophil and macrophage extracellular traps (NETs/METs), structures formed through specialized types of cell death. In this review, we propose that the KD-like pathogenesis observed in COVID-19infected children could arise from infection of resident macrophages resulting in activation of NLRP3 inflammasomes and release of IL-1 beta in a genetically predisposed subset of infected children, mediated via NET/MET dysregulation and overproduction. We also propose potential avenues of diagnosis and treatment that could be utilized to aid such patients.
ABSTRACT
The currently ongoing COVID-19 pandemic has driven an urgent need to develop treatments and preventative measures against this phenomenon, particularly given the devastation that the ongoing situation has wrought on the global economics, medical, and social arenas. This dire situation has driven a monumental global effort has tourgently produce suitable vaccines to prevent and stem COVID-19. However, there remains a lack of consensus as to what constitutes a safe and effective COVID-19 vaccine strategy, with current trials not designed to detect a reduction in the likelihood of severe illness and stemming of disease transmission. Critically, however, most indicators suggest that millions of high-risk individuals will not gain access to vaccines any time soon (persons ≥ 65 years of age, persons with underlying conditions, the economically deprived, and various ethnic minorities). Considering such concerns, perhaps deployment of existing vaccinations with documented results could be deployed to assist in interim efforts to stem the spread of COVID-19. Some vaccines such as the Bacilli-Calmette-Guerin (BCG) vaccine may confer non-specific protection or effects (NSE) against disease other than its intended target. In this article, we discuss recent efforts to investigate how such approaches may be beneficial and present our hypothesis that such non-specific events of similar vaccines may assist in prevention of severe disease while specific COVID-19 vaccines are further developed and made available to the most high-risk individuals.
ABSTRACT
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-forward loop, causing diffuse small vessel vasculitis in the lungs and other organs.