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.