Sodium-glucose co-transporter 2 inhibitors in COVID-19: meeting at the crossroads between heart, diabetes and infectious diseases.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new class of glucose-lowering agents which have changed the landscape of diabetes therapy, due to their remarkable cardiorenal protective properties. The attack of severe acute respiratory syndrome coronavirus 2 on the heart and kidneys shares similarities with diabetes; therefore, the notion that SGLT2i might have a role in the future management of Coronavirus Disease 2019 (COVID-19) is based on a solid pathophysiological hypothesis. SGLT2i have been proved to decrease the expression of proinflammatory cytokines, ameliorate oxidative stress and reduce sympathetic activity, thus resulting in downregulation of both systemic and adipose tissue inflammation. On the other hand, they have been linked to an increased risk of euglycemic diabetic ketoacidosis. Therefore, the efficacy and safety of SGLT2i in COVID-19 are still debatable and remain to be clarified by ongoing randomized trials, to assess whether the benefits of treatment with these drugs outweigh the potential risks.

Impact and Determinants of High-Sensitivity Cardiac Troponin-T Concentration in Patients With COVID-19 Admitted to Critical Care.

Cardiac Troponin (hs-TnT) elevation has been reported in unselected patients hospitalized with COVID-19 however the mechanism and relationship with mortality remain unclear. Consecutive patients admitted to a high-volume intensive care unit (ICU) in London with severe COVID-19 pneumonitis were included if hs-TnT concentration at admission was known. Kaplan-Meier survival analysis performed, with cohorts classified a priori by multiples of the upper limit of normal (ULN). 277 patients were admitted during a 7-week period in 2020; 176 were included (90% received invasive ventilation). hs-TnT at admission was 16.5 (9.0 to 49.3) ng/L, 56% had concentrations >ULN. 56 patients (31.8%) died during the index admission. Admission hs-TnT level was lower in survivors (12.0 (8.0-27.8) vs 28.5 (14.0 to 81.0) ng/L, p = 0.001). Univariate predictors of mortality were age, APACHE-II Score and admission hs-TnT (HR 1.73, p = 0.007). By multivariate regression, only age (HR 1.33, CI: 1.16.to 1.51, p < 0.01) and admission hs-TnT (HR 1.94, CI: 1.22 to 3.10, p = 0.006) remained predictive. Survival was significantly lower when admission hs-TnT was >ULN (log-rank p-value<0.001). Peak hs-TnT was higher in those who died but was not predictive of death after adjustment for other factors. In conclusion, in critically ill patients with COVID-19 pneumonitis, the hs-TnT level at admission is a powerful independent predictor of the likelihood of surviving to discharge from ICU. In most cases, hs-TnT elevation does not represent major myocardial injury but acts as a sensitive integrated biomarker of global stress. Whether stratification based on admission Troponin level could be used to guide prognostication and management warrants further evaluation.