Endothelial cells line the inner portion of the heart, blood vessels, and lymphatic vessels; a basal membrane of extracellular matrix lines the extraluminal side of endothelial cells. The apical side of endothelial cells is the site for the glycocalyx, which is a complex network of macromolecules, including cell-bound proteoglycans and sialoproteins. Sepsis-associated alterations of this structure may compromise endothelial permeability with associated interstitial fluid shift and generalized edema. Indeed, in sepsis, the glycocalyx acts as a target for inflammatory mediators and leukocytes, and its ubiquitous nature explains the damage of tissues that occurs distant from the original site of infection. Inflammatory-mediated injury to glycocalyx can be responsible for a number of specific clinical effects of sepsis, including acute kidney injury, respiratory failure, and hepatic dysfunction. Moreover, some markers of glycocalyx degradation, such as circulating levels of syndecan or selectins, may be used as markers of endothelial dysfunction and sepsis severity. Although a great deal of experimental evidence shows that alteration of glycocalyx is widely involved in endothelial damage caused by sepsis, therapeutic strategies aiming at preserving its integrity did not significantly improve the outcome of these patients.

First isolated in China in early 2020, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the novel coronavirus responsible for the ongoing pandemic of Coronavirus Disease 2019 (COVID-19). The disease has been spreading rapidly across the globe, with the largest burden falling on China, Europe, and the United States. COVID-19 is a new clinical syndrome, characterized by respiratory symptoms with varying degrees of severity, from mild upper respiratory illness to severe interstitial pneumonia and acute respiratory distress syndrome, aggravated by thrombosis in the pulmonary microcirculation. Three main phases of disease progression have been proposed for COVID-19: an early infection phase, a pulmonary phase, and a hyperinflammation phase. Although current understanding of COVID-19 treatment is mainly derived from small uncontrolled trials that are affected by a number of biases, strong background noise, and a litany of confounding factors, emerging awareness suggests that drugs currently used to treat COVID-19 (antiviral drugs, antimalarial drugs, immunomodulators, anticoagulants, and antibodies) should be evaluated in relation to the pathophysiology of disease progression. Drawing upon the dramatic experiences taking place in Italy and around the world, here we review the changes in the evolution of the disease and focus on current treatment uncertainties and promising new therapies.

Both the hyperproduction of oxygen free radicals (OFR) and the weakening of natural scavenging mechanisms have been implicated as contributors to multiple organ failure in septic shock. This study examined whether the antioxidants glutathione (GSH) and N-acetyl-L-cysteine (NAC) play a protective role against damage by OFR in early septic shock. We randomly entered 30 patients with septic shock into one of three groups within 24 h of diagnosis. All of the patients received septic shock therapy, including parenteral nutrition, antibiotics, and volume-expanding and inotropic agents. One group (Group B) also received 70 mg/kg/d of intravenous GSH, and a second group (Group C), 70 mg/kg/d of intravenous GSH and 75 mg/kg/d of intravenous NAC. The protection against OFR damage was evaluated by measuring expired ethane, plasma malondialdehyde, erythrocyte deformability, complement activation, and clinical scores at admission and on Days 3 and 5 of treatment. A significant decrease in peroxidative indexes was observed at Day 5 in Group B as compared with both the control group and basal values. The decrease in peroxidative indexes was even more marked in Group C. Clinical scores in this group were also significantly improved. In conclusion, the administration of high doses of NAC added to GSH significantly decreased the peroxidative stress of patients with septic shock.