Beneficial non-anticoagulant mechanisms underlying heparin treatment of COVID-19 patients

Abstract

Coronavirus disease-2019 (COVID-19) is associated with severe inflammation in mainly the lung, and kidney. Reports suggest a beneficial effect of the use of heparin/low molecular weight heparin (LMWH) on mortality in COVID-19. In part, this beneficial effect could be explained by the anticoagulant properties of heparin/LMWH. Here, we summarise potential beneficial, non-anticoagulant mechanisms underlying treatment of COVID-19 patients with heparin/LMWH, which include: (i) Inhibition of heparanase activity, responsible for endothelial leakage; (ii) Neutralisation of chemokines, and cytokines; (iii) Interference with leukocyte trafficking; (iv) Reducing viral cellular entry, and (v) Neutralisation of extracellular cytotoxic histones. Considering the multiple inflammatory and pathogenic mechanisms targeted by heparin/LMWH, it is warranted to conduct clinical studies that evaluate therapeutic doses of heparin/LMWH in COVID-19 patients. In addition, identification of specific heparin-derived sequences that are functional in targeting non-anticoagulant mechanisms may have even higher therapeutic potential for COVID-19 patients, and patients suffering from other inflammatory diseases.

The interplay between neutrophils, complement, and microthrombi in COVID-19

“…Patients with COVID-19 are increasingly being treated with the combination of heparin-based anticoagulation and dexamethasone. The former may modulate NETs by the neutralization of cytotoxic histones [ 86 ] and by the potentiation of NET clearance through DNase I [ 30 ]. At the same time, corticosteroids such as dexamethasone can also reduce NET formation in vivo [ 87 ], most likely through the modulation of the inflammatory mediators that activate neutrophils.…”

A review of potential suggested drugs for coronavirus disease (COVID-19) treatment

“…Besides, patients with severe disease and prolonged immobility are exposed to a high risk of venous thromboembolism (VTE), and acute pulmonary embolism (PE) or deep vein thrombosis (DVT) may be experienced in patients with mechanical ventilation. Numerous randomized controlled trials have been designed to assess anticoagulation risks and efficacy in patients with COVID-19 ( Buijsers et al, 2020 ; Fletcher-Sandersjöö and Bellander, 2020 ). By its spike (S) protein, SARS-CoV-2 binds to the TMPRSS2 receptor, and this viral entry is facilitated by the ACE-2 receptor ( Hoffmann et al, 2020a ).…”

Arrhythmias in the Age of Coronavirus Disease 2019

“…Heparin may be the anticoagulant of choice in inpatients due to its anti-inflammatory and antiviral properties. 14 When cardioversion is necessary, cardiac computed tomography may be used to avoid transesophageal echocardiography.…”