Thrombo-Inflammation in COVID-19 and Sickle Cell Disease: Two Faces of the Same Coin

• Published in: Biomedicines 2023-01, Vol.11 (2), p.338
• Main Authors: Chiang, Kate Chander, Gupta, Ajay, Sundd, Prithu, Krishnamurti, Lakshmanan
• Format: Article
• Language: English
• Subjects: African Americans; Age; Blood platelets; Cell activation; Clinical trials; Complement activation; Coronaviruses; COVID-19; Embolisms; Endothelial cells; Heart failure; Hemoglobin; Hospitalization; Hypertension; Infections; Inflammation; Ischemia; Kidney diseases; Leukocytes (neutrophilic); Macrophages; Mortality; pain; Pandemics; Pathophysiology; Patients; Physiological aspects; Platelets; Pneumonia; Quality of life; Review; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Sickle cell anemia; Sickle cell disease; Stroke; Therapeutic targets; Thrombosis; thromboxane; Thromboxane A2; vaso-occlusive crisis
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines11020338

People with sickle cell disease (SCD) are at greater risk of severe illness and death from respiratory infections, including COVID-19, than people without SCD (Centers for Disease Control and Prevention, USA). Vaso-occlusive crises (VOC) in SCD and severe SARS-CoV-2 infection are both characterized by thrombo-inflammation mediated by endothelial injury, complement activation, inflammatory lipid storm, platelet activation, platelet-leukocyte adhesion, and activation of the coagulation cascade. Notably, lipid mediators, including thromboxane A , significantly increase in severe COVID-19 and SCD. In addition, the release of thromboxane A from endothelial cells and macrophages stimulates platelets to release microvesicles, which are harbingers of multicellular adhesion and thrombo-inflammation. Currently, there are limited therapeutic strategies targeting platelet-neutrophil activation and thrombo-inflammation in either SCD or COVID-19 during acute crisis. However, due to many similarities between the pathobiology of thrombo-inflammation in SCD and COVID-19, therapies targeting one disease may likely be effective in the other. Therefore, the preclinical and clinical research spurred by the COVID-19 pandemic, including clinical trials of anti-thrombotic agents, are potentially applicable to VOC. Here, we first outline the parallels between SCD and COVID-19; second, review the role of lipid mediators in the pathogenesis of these diseases; and lastly, examine the therapeutic targets and potential treatments for the two diseases.