Circulating ACE2 level and zinc/albumin ratio as potential biomarkers for a precision medicine approach to COVID-19.

Highly mutable influenza is successfully countered based on individual susceptibility and similar precision-like medicine approach should be effective against SARS-COV-2. Among predictive markers to bring precision medicine to COVID-19, circulating ACE2 has potential features being upregulated in both severe COVID-19 and predisposing comorbidities. Spike SARS-CoVs were shown to induce ADAM17-mediated shedding of enzymatic active ACE2, thus accounting for its increased activity that has also been suggested to induce positive feedback loops leading to COVID-19-like manifestations. For this reason, pre-existing ACE2 activity and inhibition of ACE2/ADAM17 zinc-metalloproteases through zinc chelating agents have been proposed to predict COVID-19 outcome before infection and to protect from COVID-19, respectively. Since most diagnostic laboratories are not equipped for enzymatic activity determination, other potential predictive markers of disease progression exploitable by diagnostic laboratories were explored. Concentrations of circulating albumin, zinc, ACE2 protein and its activity were investigated in healthy, diabetic (COVID-19-susceptible) and SARS-CoV-2-negative COVID-19 individuals. ACE2 both protein levels and activity significantly increased in COVID-19 and diabetic patients. Abnormal high levels of ACE2 characterised a subgroup (16-19%) of diabetics, while COVID-19 patients were characterised by significantly higher zinc/albumin ratios, pointing to a relative increase of albumin-unbound zinc species, such as free zinc ones. Data on circulating ACE2 levels are in line with the hypothesis that they can drive susceptibility to COVID-19 and elevated zinc/albumin ratios support the therapeutic use of zinc chelating inhibitors of ACE2/ADAM17 zinc-metalloproteases in a targeted therapy for COVID-19.

Vitamin D and Male Sexual Function: A Transversal and Longitudinal Study.

BACKGROUND: The effects of vitamin D on sexual function are very unclear. Therefore, we aimed at evaluating the possible association between vitamin D and sexual function and at assessing the influence of vitamin D administration on sexual function. METHODS: We retrospectively studied 114 men by evaluating clinical, biochemical, and sexual parameters. A subsample (n = 41) was also studied longitudinally before and after vitamin D replacement therapy. RESULTS: In the whole sample, after performing logistic regression models, higher levels of 25(OH) vitamin D were significantly associated with high values of total testosterone and of all the International Index of Erectile Function (IIEF) questionnaire parameters. On the other hand, higher levels of total testosterone were positively and significantly associated with high levels of erectile function and IIEF total score. After vitamin D replacement therapy, total and free testosterone increased and erectile function improved, whereas other sexual parameters did not change significantly. At logistic regression analysis, higher levels of vitamin D increase (Δ-) were significantly associated with high values of Δ-erectile function after adjustment for Δ-testosterone. CONCLUSIONS: Vitamin D is important for the wellness of male sexual function, and vitamin D administration improves sexual function.