Abstract
The impact of the COVID-19 pandemic has been dramatic worldwide, with China, Italy, and now US at its epicenter. Researchers and clinicians are studying and testing different approaches in the attempt to prevent the infection and minimize its severity. Major efforts are focused on optimizing mechanical ventilation, antiviral, and supportive treatment; however, the role of heparin and low molecular weight (LMW) heparin in this setting has been largely overlooked. This review summarizes the available evidence about the role of heparan sulfate as a key entry mechanism for SARS-CoV-2; the efficacy of heparin and LMW heparin in counteracting its entry into the cell, the recent experimental findings obtained in in vitro studies using the LMW heparin enoxaparin Inhixa®, the role of heparin and LMW heparin in modulating the cytokine storm, and the evidence for the use of LMW heparin in the prevention and treatment of the thromboembolic complications of COVID-19. The available evidence suggests that LMW heparin appears as a promising tool in the treatment of COVID-19. Whether its systematic use is associated with a reduction in complications and ultimately mortality of these patients is being tested in several studies starting worldwide.
Highlights
The spread of new coronavirus (SARS-CoV-2) has been recently declared a pandemic by the World Health Organization (WHO)
Four steps appear fundamental in the clinical outcome of COVID-19 infected patients: First, the cell infection by the virus; second, the so-called cytokine storm, i.e., the inflammatory response triggered by the infection; third, the pulmonary infiltration leading to a significant reduction in oxygen saturation; and lastly, the thromboembolic complications of the inflammatory response, contributing to rapid deterioration of the clinical status and death
Data are emerging indicating that diffuse bilateral pulmonary inflammation observed in COVID-19 is associated with a novel pulmonary-specific vasculopathy, which has been termed pulmonary intravascular coagulopathy as distinct to disseminated intravascular coagulation (Fogarty et al, 2020)
Summary
The spread of new coronavirus (SARS-CoV-2) has been recently declared a pandemic by the World Health Organization (WHO). More recent data indicated that the human coronavirus NL63 similar to SARS-CoV-2 S1 RBD undergoes conformational change upon heparin binding, and this decreases the adhesion and the interaction with the ACE receptors. Yang et al (2020) showed by native mass spectrometry that both short (pentasaccharide) and relatively long (eicosasaccharide) heparin oligomers form 1:1 complexes with S1 protein receptor binding domain, supporting the existence of a single binding site This association induces a conformational change with an important reduction of the ability to associate with ACE2. The available evidence indicates that heparan sulfate has a central role in the adhesion of the virus to the cell surface and that heparin leads to a conformational change of the SARS-CoV2 surface protein and limits its interaction with the ACE2 receptor, inhibiting SARS-CoV-2 infection (Kim et al, 2020). Heparan sulfate manipulation or the inhibition of viral adhesion by exogenous heparin can constitute new therapeutic opportunities (Kim et al, 2020)
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