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

Abstract

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 A2, significantly increase in severe COVID-19 and SCD. In addition, the release of thromboxane A2 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.

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“…Also, SCD leads to an increased chance of several diseases, such as pulmonary hypertension, chronic lung disease, and kidney failure [ 33 ]. In this vein, chronic pulmonary injury from thrombo-inflammation caused by COVID-19 exacerbates SCD complications and increases mortality rates [ 34 ]. Likewise, acute vaso-occlusive crisis (VOC) attributed to SCD in COVID-19 patients increases the likelihood of pulmonary embolism (PE) and ACS [ 35 ].…”