Your browser doesn't support javascript.
Neutrophil Extracellular Traps and By-Products Play a Key Role in COVID-19: Pathogenesis, Risk Factors, and Therapy.
Thierry, Alain R; Roch, Benoit.
  • Thierry AR; Research Institute of Cancerology of Montpellier, INSERM U1194, IRCM, ICM, Montpellier University, F-34298 Montpellier, France.
  • Roch B; Respiratory Medicine, University Hospital of Montpellier, Montpellier University, F-34298 Montpellier, France.
J Clin Med ; 9(9)2020 Sep 11.
Article in English | MEDLINE | ID: covidwho-892446
Semantic information from SemMedBD (by NLM)
1. COVID-19 CAUSES Inflammatory Response
Subject
COVID-19
Predicate
CAUSES
Object
Inflammatory Response
2. Neutrophil Extracellular Traps LOCATION_OF 2019 novel coronavirus
Subject
Neutrophil Extracellular Traps
Predicate
LOCATION_OF
Object
2019 novel coronavirus
3. Pharmaceutical Preparations INTERACTS_WITH Elastases
Subject
Pharmaceutical Preparations
Predicate
INTERACTS_WITH
Object
Elastases
4. metformin INTERACTS_WITH Elastases
Subject
metformin
Predicate
INTERACTS_WITH
Object
Elastases
5. COVID-19 CAUSES Inflammatory Response
Subject
COVID-19
Predicate
CAUSES
Object
Inflammatory Response
6. Neutrophil Extracellular Traps LOCATION_OF 2019 novel coronavirus
Subject
Neutrophil Extracellular Traps
Predicate
LOCATION_OF
Object
2019 novel coronavirus
7. Pharmaceutical Preparations INTERACTS_WITH Elastases
Subject
Pharmaceutical Preparations
Predicate
INTERACTS_WITH
Object
Elastases
8. metformin INTERACTS_WITH Elastases
Subject
metformin
Predicate
INTERACTS_WITH
Object
Elastases
ABSTRACT
Understanding of the pathogenesis of the coronavirus disease-2019 (COVID-19) remains incomplete, particularly in respect to the multi-organ dysfunction it may cause. We were the first to report the analogous biological and physiological features of COVID-19 pathogenesis and the harmful amplification loop between inflammation and tissue damage induced by the dysregulation of neutrophil extracellular traps (NETs) formation. Given the rapid evolution of this disease, the nature of its symptoms, and its potential lethality, we hypothesize that COVID-19 progresses under just such an amplifier loop, leading to a massive, uncontrolled inflammation process. Here, we describe in-depth the correlations of COVID-19 symptoms and biological features with those where uncontrolled NET formation is implicated in various sterile or infectious diseases. General clinical conditions, as well as numerous pathological and biological features, are analogous with NETs deleterious effects. Among NETs by-products implicated in COVID-19 pathogenesis, one of the most significant appears to be elastase, in accelerating virus entry and inducing hypertension, thrombosis and vasculitis. We postulate that severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) may evade innate immune response, causing uncontrolled NETs formation and multi-organ failure. In addition, we point to indicators that NETS-associated diseases are COVID-19 risk factors. Acknowledging that neutrophils are the principal origin of extracellular and circulating DNA release, we nonetheless, explain why targeting NETs rather than neutrophils themselves may in practice be a better strategy. This paper also offers an in-depth review of NET formation, function and pathogenic dysregulation, as well as of current and prospective future therapies to control NETopathies. As such, it enables us also to suggest new therapeutic strategies to fight COVID-19. In combination with or independent of the latest tested approaches, we propose the evaluation, in the short term, of treatments with DNase-1, with the anti-diabetic Metformin, or with drugs targeting elastase (i.e., Silvelestat). With a longer perspective, we also advocate a significant increase in research on the development of toll-like receptors (TLR) and C-type lectin-like receptors (CLEC) inhibitors, NET-inhibitory peptides, and on anti-IL-26 therapies.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Language: English Clinical aspect: Etiology Year: 2020

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Language: English Clinical aspect: Etiology Year: 2020
...