Erythrocytes increase endogenous sphingosine 1-phosphate levels as an adaptive response to SARS-CoV-2 infection.

Low plasma levels of the signaling lipid metabolite sphingosine 1-phosphate (S1P) are associated with disrupted endothelial cell (EC) barriers, lymphopenia and reduced responsivity to hypoxia. Total S1P levels were also reduced in 23 critically ill patients with coronavirus disease 2019 (COVID-19), and the two main S1P carriers, serum albumin (SA) and high-density lipoprotein (HDL) were dramatically low. Surprisingly, we observed a carrier-changing shift from SA to HDL, which probably prevented an even further drop in S1P levels. Furthermore, intracellular S1P levels in red blood cells (RBCs) were significantly increased in COVID-19 patients compared with healthy controls due to up-regulation of S1P producing sphingosine kinase 1 and down-regulation of S1P degrading lyase expression. Cell culture experiments supported increased sphingosine kinase activity and unchanged S1P release from RBC stores of COVID-19 patients. These observations suggest adaptive mechanisms for maintenance of the vasculature and immunity as well as prevention of tissue hypoxia in COVID-19 patients.

Camostat Mesylate May Reduce Severity of Coronavirus Disease 2019 Sepsis: A First Observation.

Severe acute respiratory syndrome coronavirus 2 cell entry depends on angiotensin-converting enzyme 2 and transmembrane serine protease 2 and is blocked in cell culture by camostat mesylate, a clinically proven protease inhibitor. Whether camostat mesylate is able to lower disease burden in coronavirus disease 2019 sepsis is currently unknown. DESIGN: Retrospective observational case series. SETTING: Patient treated in ICU of University hospital Göttingen, Germany. PATIENTS: Eleven critical ill coronavirus disease 2019 patients with organ failure were treated in ICU. INTERVENTIONS: Compassionate use of camostat mesylate (six patients, camostat group) or hydroxychloroquine (five patients, hydroxychloroquine group). MEASUREMENTS AND MAIN RESULTS: Clinical courses were assessed by Sepsis-related Organ Failure Assessment score at days 1, 3, and 8. Further, viral load, oxygenation, and inflammatory markers were determined. Sepsis-related Organ Failure Assessment score was comparable between camostat and hydroxychloroquine groups upon ICU admission. During observation, the Sepsis-related Organ Failure Assessment score decreased in the camostat group but remained elevated in the hydroxychloroquine group. The decline in disease severity in camostat mesylate treated patients was paralleled by a decline in inflammatory markers and improvement of oxygenation. CONCLUSIONS: The severity of coronavirus disease 2019 decreased upon camostat mesylate treatment within a period of 8 days and a similar effect was not observed in patients receiving hydroxychloroquine. Camostat mesylate thus warrants further evaluation within randomized clinical trials.