Immunothrombosis in Acute Respiratory Dysfunction of COVID-19

Abstract

COVID-19 is an acute, complex disorder that was caused by a new β-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on current reports, it was surprising that the characteristics of many patients with COVID-19, who fulfil the Berlin criteria for acute respiratory distress syndrome (ARDS), are not always like those of patients with typical ARDS and can change over time. While the mechanisms of COVID-19-related respiratory dysfunction in COVID-19 have not yet been fully elucidated, pulmonary microvascular thrombosis is speculated to be involved. Considering that thrombosis is highly related to other inflammatory lung diseases, immunothrombosis, a two-way process that links coagulation and inflammation, seems to be involved in the pathophysiology of COVID-19, including respiratory dysfunction. Thus, the current manuscript will describe the proinflammatory milieu in COVID-19, summarize current evidence of thrombosis in COVID-19, and discuss possible interactions between these two.

Keywords: COVID-19; inflammation; respiratory dysfunction; therapeutic; thrombosis.

Figure 1

Schematic diagram of immunothrombosis in COVID-19. SARS-CoV-2 infection typically begins in epithelial cells of the respiratory tract, which can further promote the cytokine storm and infiltration of neutrophil. The cytokine storm can result in endothelial dysfunction, tissue factor (TF) overexpression, and the platelets activation, which initiates the TF-dependent coagulation process. The release of NETs promotes platelet–neutrophil aggregation and neutrophil activation in the bloodstream. Furthermore, the cytokine storm also suppresses antithrombin, APC and PAI-1, which impair anticoagulation and decrease fibrinolysis. In addition, SARS-CoV-2 can also directly impair ECs. The above factors collectively facilitate the generation of thrombus in COVID-19.