Beyond anticoagulation, there may be alternative beneficial mechanisms of action for heparin in patients with COVID-19 including direct SARS-CoV-2 antiviral activity. In a similar fashion to the related viruses severe acute respiratory coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), host cell fusion and entry are thought to be accomplished in SARS-CoV-2 infection via binding of the viral spike protein to host angiotensin-converting enzyme 2 (ACE2) receptors. Cofactors for this binding are incompletely understood for SARS-CoV-2; however, in vitro studies have demonstrated that cell surface heparan sulfate (the class of glycosaminoglycans of which heparin is composed) is essential for entry and infectivity with human coronavirus NL63 (23) and SARS-CoV (19). Heparan sulfate is thought to interact with the spike protein as an adhesion molecule coreceptor, which may be the first step in facilitating the interaction of SARS-CoV and the ACE2 receptor (23). It has recently been discovered that concordant with other coronaviruses, the SARS-CoV-2 spike protein also interacts with heparan sulfate, and with a higher affinity than either SARS-CoV or MERS-CoV spike proteins (17). In this study by Kim et al., the SARS-CoV-2 spike protein demonstrated extremely strong (and nearly irreversible) binding to heparin using surface plasmon resonance.