Severe contagious respiratory disease—COVID-19—caused by the SARS-CoV-2 coronavirus, can lead to fatal respiratory failure associated with an excessive inflammatory response. Infiltration and spread of SARS-CoV-2 are based on the interaction between the virus’ structural protein S and the cell’s receptor–angiotensin-converting enzyme 2 (ACE2), with the simultaneous involvement of human trans-membrane protease, serine 2 (TMPRSS2). Many scientific reports stress the importance of elevated recruitment and activity of neutrophils, which can form extracellular neutrophil traps (NETs) playing a significant role in the mechanism of combating pathogens, in the pathogenesis of COVID-19. Excessive generation of NETs during prolonged periods of inflammation predisposes for the occurrence of undesirable reactions including thromboembolic complications and damage to surrounding tissues and organs. Within the present manuscript, we draw attention to the impact of NET generation on the severe course of COVID-19 in patients with concurrent cardiovascular and metabolic diseases. Additionally, we indicate the necessity to explore not only the cellular but also the molecular bases of COVID-19 pathogenesis, which may aid the development of dedicated therapies meant to improve chances for the successful treatment of patients. We also present new directions of research into medications that display NETs formation regulatory properties as potential significant therapeutic strategies in the progress of COVID-19.
27 December 2016 in Scandinavian Journal of Immunology
Neutrophils (PMNs) play a key role in innate defence mechanisms. Generally, PMNs were considered to have a homogeneous population of mature and diversified cells. It seems, however, that their pleiotropic action results from the existence of different subpopulations in this group of cells. There are data that confirm the involvement of PMNs in the direct activation of other cells in non-specific response, as well as specialised cells in specific response. For example, there have been observations of PMNs with different levels of activity in relation to lymphocytes, and a population was identified which had characteristics similar to those of cells which are capable of presenting antigens. There are also reports of PMNs which demonstrate different survival time or capacity for chemotaxis. Other studies suggest that the neutrophil response to Staphylococcus aureus is diverse (not identical among all neutrophil). There are also reports of PMNs with varying activity during inflammation, which might explain many as yet unknown pathophysiological aspects of their hyperreactivity. The functional dualism of PMNs in the course of neoplastic disorders raises a lot of controversy. This paper presents the current state of knowledge of the heterogeneity of PMNs and their potential roles in different stages of disease.