Coronavirus disease 2019 (COVID-19) has spread rapidly throughout the globe. It is associated with significant mortality, particularly in at-risk groups with poor prognostic features at hospital admission. 1 The spectrum of disease is broad but among hospitalised patients with COVID-19, pneumonia, sepsis, respiratory failure, and acute respiratory distress syndrome (ARDS) are frequently encountered complications. 1 The pathophysiology of severe acute respiratory syndrome cor ona virus 2 (SARS-CoV-2)-induced ARDS has similarities to that of severe community-acquired pneumonia caused by other viruses or bacteria. 2, 3 The overproduction of early response proinflammatory cytokines (tumour necrosis factor [TNF], IL-6, and IL-1β) results in what has been described as a cytokine storm, leading to an increased risk of vascular hyperpermeability, multiorgan failure, and eventually death when the high cytokine concentrations are unabated over time. 4 Therefore, therapeutic strategies under investigation are targeting the overactive cytokine response with anticytokine therapies or immunomodulators, but this must be balanced with maintaining an adequate inflammatory response for pathogen clearance. Activation of coagulation pathways during the immune response to infection results in overproduction of proinflammatory cytokines leading to multiorgan injury. Although the main function of thrombin is to promote clot formation by activating platelets and by converting fibrinogen to fibrin, 5 thrombin also exerts multiple cellular effects and can further augment inflammation via proteinaseactivated receptors (PARs), principally PAR-1. 5 Thrombin generation is tightly controlled by negative feedback loops and physiological anticoagulants, such as antithrombin III, tissue factor pathway inhibitor, and the protein C system. 5 During inflammation, all three of these control mechanisms can be impaired, with reduced anti coagulant concentrations due to reduced production and increasing consumption. This defective pro coagulant–anticoagulant balance predisposes to the development of microthrombosis, disseminated intra vascular coagulation, and multiorgan failure—evidenced in severe COVID-19 pneumonia with raised d-dimer concentrations being a poor prognostic feature and disseminated intravascular coagulation common in non-survivors. 1, 6

The finding of increased d-dimer levels in patients with COVID-19 has prompted questions regarding coexistence of venous thromboembolism exacerbating ventilation–perfusion mismatch, and some studies have shown that pulmonary emboli are prevalent. 7 However, due to increased risk of bleeding and despondence related to previous negative trials of endogenous anticoagulants in sepsis, clinicians might be reluctant to offer it to all. Outside of the prevention and management of venous thrombo embolism, it is clear that effects of coagulation activation go beyond clotting and crosstalk between coagulation and inflammation can significantly affect disease progression and lead to poor outcome. Prophylactic dose low molecular weight heparin (LMWH) is recommended for hospitalised patients with COVID-19 to prevent venous thromboembolism and treatment dose LMWH is contemplated for those with significantly raised d-dimer concentrations due to concerns of thrombi in the pulmonary circulation; but LMWH also has anti-inflammatory properties that might be beneficial in COVID-19. In this context, it is therefore paramount to look at the role of PAR antagonists and other