Fig. 1

a Lung injury in coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE-2) primarily on type II alveolar cells. After endocytosis of the viral complex, surface ACE-2 is downregulated, resulting in unopposed angiotensin II accumulation. SARS-CoV-2 further causes lung injury through activation of residential macrophages, lymphocyte apoptosis and neutrophils. The macrophages produce cytokines and chemokines, resulting in a cytokine storm. Inflammatory exudate rich in plasma-borne coagulation factors enters the alveolar space, followed by expression of tissue factor by alveolar epithelial cells and macrophages and the formation of fibrin and the hyaline membrane. Neutrophils in the alveoli cause formation of NETs, composed of extracellular DNA, cytotoxic histones and neutrophil elastase, which cause further lung injury. COVID-19 also induces microvascular endothelial damage leading to increased permeability, expression of tissue factor with coagulation activation and thrombus formation. b Proposed effects of inhaled nebulised unfractionated heparin (UFH) in COVID-19 lung injury. UFH prevents SARS-CoV-2 from binding to ACE-2 and from entering the alveolar cells. UFH reduces formation of the hyaline membrane and microvascular thrombosis, counteracts the hyperinflammation and the formation of NETs, increases NO release with vasodilation and also has mucolytic properties. NETs, neutrophil extracellular traps; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; ACE-2, angiotensin-converting enzyme 2; COVID-19, coronavirus disease 2019. Permission was granted by © Beth Croce, Bioperspective.com to reuse this figure