Comprehensive Landscape of Heparin Therapy for COVID-19

•Heparin, used clinically over 80 years, has shown potential for COVID-19 treatment.•The evidence and possible mechanisms of heparin for COVID-19 treatment are discussed.•The prospect of heparin therapy for COVID-19 is presented in this review. The pandemic coronavirus disease 2019 (COVID-19), caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is rapidly spreading globally. Clinical observations found that systemic symptoms caused by SARS-CoV-2 infection are attenuated when using the anticoagulant agent heparin, indicating that heparin may play other roles in managing COVID-19, in addition to prevention of pulmonary thrombosis. Several biochemical studies show strong binding of heparin and heparin-like molecules to the Spike protein, which resulted in inhibition of viral infection to cells. The clinical observations and in vitro studies argue for a potential multiple-targeting effects of heparin. However, adverse effects of heparin administration and some of the challenges using heparin therapy for SARS-CoV-2 infection need to be considered. This review discusses the pharmacological mechanisms of heparin regarding its anticoagulant, anti-inflammatory and direct antiviral activities, providing current evidence concerning the effectiveness and safety of heparin therapy for this major public health emergency.