Is digital necrosis in COVID-19 caused by neutrophil extracellular traps: Potential therapeutic strategies

Some of the COVID-19 patients present with ischemic lesions of their finger and toes. Standard anticoagulant therapy is usually unsuccessful for the treatment of this unique presentation of COVID-19. In this review current evidence is presented, which supports the hypothesis that these necrotic lesions are primarily related to the formation of neutrophil extracellular traps is blood vessels. Also, currently available and potential pharmacological methods of the management of this unique thrombotic complication are discussed. Drugs that possibly could be used in COVID-19 patients suffering from acute ischemia of distal parts of the extremities particularly comprise DNase I and DNase1L3, which could directly dissolve these extracellular webs that are mostly composed of DNA. However, at the moment, none of these enzymes are registered for an intravascular administration in humans. Lactoferrin and dipyridamole are other pharmaceutical agents that could potentially be used for the treatment of neutrophil extracellular traps-evoked digital ischemia. These agents exhibit prophylactic activity against excessive formation of these extracellular structures. Such an experimental treatment should probably be accompanied by standard antithrombotic management with heparin. Open-label and then randomized trials are needed to confirm feasibility, safety and efficacy of the above-suggested management of critically ill COVID-19 patients.