Soluble P2X7 Receptor Is Elevated in the Plasma of COVID-19 Patients and Correlates With Disease Severity.

Inflammation is a tightly coordinated response against bacterial and viral infections, triggered by the production of pro-inflammatory cytokines. SARS-CoV-2 infection induces COVID-19 disease, characterized by an inflammatory response mediated through the activation of the NLRP3 inflammasome, which results in the production of IL-1ß and IL-18 along with pyroptotic cell death. The NLRP3 inflammasome could be also activated by sterile danger signals such as extracellular ATP triggering the purinergic P2X7 receptor. Severe inflammation in the lungs of SARS-CoV-2-infected individuals is associated with pneumonia, hypoxia and acute respiratory distress syndrome, these being the causes of death associated with COVID-19. Both the P2X7 receptor and NLRP3 have been considered as potential pharmacological targets for treating inflammation in COVID-19. However, there is no experimental evidence of the involvement of the P2X7 receptor during COVID-19 disease. In the present study, we determined the concentration of different cytokines and the P2X7 receptor in the plasma of COVID-19 patients and found that along with the increase in IL-6, IL-18 and the IL-1 receptor antagonist in the plasma of COVID-19 patients, there was also an increase in the purinergic P2X7 receptor. The increase in COVID-19 severity and C-reactive protein concentration positively correlated with increased concentration of the P2X7 receptor in the plasma, but not with the IL-18 cytokine. The P2X7 receptor was found in the supernatant of human peripheral blood mononuclear cells after inflammasome activation. Therefore, our data suggest that determining the levels of the P2X7 receptor in the plasma could be a novel biomarker of COVID-19 severity.

Severe COVID-19 after liver transplantation, surviving the pitfalls of learning on-the-go: Three case reports.

BACKGROUND: The novel coronavirus 2019 (COVID-19) pandemic has dramatically transformed the care of the liver transplant patient. In patients who are immunosuppressed and with multiple comorbidities, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with increased severity and mortality. The main objective of this report is to communicate our experience in the therapeutic management of SARS-CoV-2 infection in 3 liver transplant patients. Secondly, we stress the management and investigation of the contagious spreading into a liver transplant ward. CASE SUMMARY: The patients were two women (aged 61 years and 62 years) and one man (aged 68 years), all of them having recently received a liver transplant. All three patients required intensive care unit admission and invasive mechanical ventilation. Two of them progressed severely until death. The other one, who received tocilizumab, had a good recovery. In the outbreak, the wife of one of the patients and four healthcare professionals involved in their care were also infected. CONCLUSION: We illustrate in detail the evolution of a nosocomial COVID-19 outbreak in a liver transplant ward. We believe that these findings will contribute to a better understanding of the natural history of the disease and will improve the treatment of the liver transplant patient with COVID-19.