Platelet caspase-1 and Bruton tyrosine kinase activation in patients with COVID-19 is associated with disease severity and reversed in vitro by ibrutinib.

Background: Severity of coronavirus disease 2019 (COVID-19) is often associated with thrombotic complications and cytokine storm leading to intensive are unit (ICU) admission. Platelets are known to be responsible for abnormal hemostasis parameters (thrombocytopenia, raised D-dimers, and prolonged prothrombin time) in other viral infections through the activation of the nucleotide-binding domain leucine repeat rich containing protein 3 inflammasome induced by signaling pathways driven by Bruton tyrosine kinase (BTK) and leading to caspase-1 activation.

Objectives: We hypothesized that caspase-1 activation and the phosphorylation of BTK could be associated with the severity of the disease and that ibrutinib, a BTK inhibitor, could inhibit platelet activation.

Erythrocyte type 1 equilibrative nucleoside transporter expression in sickle cell disease and sickle cell trait.

Hypoxia-mediated red blood cell (RBC) sickling is central to the pathophysiology of sickle cell disease (SCD). The signalling nucleoside adenosine is thought to play a significant role in this process. This study investigated expression of the erythrocyte type 1 equilibrative nucleoside transporter (ENT1), a key regulator of plasma adenosine, in adult patients with SCD and carriers of sickle cell trait (SCT).

Plasma microparticles of intubated COVID-19 patients cause endothelial cell death, neutrophil adhesion and netosis, in a phosphatidylserine-dependent manner.

COVID-19 has compelled scientists to better describe its pathophysiology to find new therapeutic approaches. While risk factors, such as older age, obesity, and diabetes mellitus, suggest a central role of endothelial cells (ECs), autopsies have revealed clots in the pulmonary microvasculature that are rich in neutrophils and DNA traps produced by these cells, called neutrophil extracellular traps (NETs.) Submicron extracellular vesicles, called microparticles (MPs), are described in several diseases as being involved in pro-inflammatory pathways.