COVID-19, Cation Dysmetabolism, Sialic Acid, CD147, ACE2, Viroporins, Hepcidin and Ferroptosis: A Possible Unifying Hypothesis

Background: iron and calcium dysmetabolism, with hyperferritinemia, hypoferremia, hypocalcemia and anemia have been documented in the majority of COVID-19 patients at later/worse stages. Furthermore, complementary to ACE2, both sialic acid (SA) molecules and CD147 proved relevant host receptors for SARS-CoV-2 entry, which explains the viral attack to multiple types of cells, including erythrocytes, endothelium and neural tissue. Several authors advocated that cell ferroptosis may be the core and final cell degenerative mechanism. Methods: a literature research was performed in several scientific search engines, such as PubMed Central, Cochrane Library, Chemical Abstract Service. More than 500 articles were retrieved until mid-December 2021, to highlight the available evidence about the investigated issues. Results: based on COVID-19 literature data, we have highlighted a few pathophysiological mechanisms, associated with virus-based cation dysmetabolism, multi-organ attack, mitochondria degeneration and ferroptosis. Our suggested elucidated pathological sequence is: a) spike protein subunit S1 docking with sialylated membrane glycoproteins/receptors (ACE2, CD147), and S2 subunit fusion with the lipid layer; b) cell membrane morpho-functional changes due to the consequent electro-chemical variations and viroporin action, which induce an altered ion channel function and intracellular cation accumulation; c) additional intracellular iron concentration due to a deregulated hepcidin-ferroportin axis, with higher hepcidin levels. Viral invasion may also affect erythrocytes/erythroid precursors, endothelial cells and macrophages, through SA and CD147 receptors, with relative hemoglobin and iron/calcium dysmetabolism. AB0 blood group, hemochromatosis, or environmental elements may represent possible factors which affect individual susceptibility to COVID-19.     Conclusions: our literature analysis confirms the combined role of SA molecules, ACE2, CD147, viroporins and hepcidin in determining the cation dysmetabolism and final ferroptosis in the cells infected by SARS-CoV-2. The altered ion channels and electrochemical gradients of the cell membrane have a pivotal role in the virus entry and cell dysmetabolism, with subsequent multi-organ immune-inflammatory degeneration and erythrocyte/hemoglobin alterations

Hepatitis C Virus Infection and Human Pancreatic β-Cell Dysfunction

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The variations of some salivary parameters as probable indices of the hereditary diabetes

Background: Diabetes has a genetic predisposition and is generally not diagnosed for many years because hyperglycemia develops gradually, without presenting the classic symptoms of diabetes. The aim of this study is to verify whether, in a potentially genetically predisposed population, men and women under the age of 50 years, at the time of the study, not suffering from diabetes can be detected using parameters derived from initial metabolic alteration indices of the possible evolution of pathology. Methods: In the hereditary and healthy group, salivary concentration of malondialdehyde, total mucins, and pH were determined. All participants in the two groups had fasting glucose level below 110 mg/dL. The results were statistically analyzed using Pearson correlation test, Mann–Whitney test, and –Student's t-test. Results: Salivary concentration of malondialdehyde statistically increased in the hereditary group vs the healthy group (P = 0.0368) as the mucins (P ≤ 0.005). The salivary pH decreased but, the values were not statistically significant (P = 0.085). Some alteration processes occur without increase in glucose levels, produced by changes in metabolic redox processes along with an increase in the salivary malondialdehyde index of oxidative stress in the body. The modification of the salivary buffer system lowers the pH, whereas increase in salivary mucins alters the value of spinnbarkeit, which measures the capacity of the mucous layer to adhere to the epithelium, causing alterations of the oral mucosa. Conclusions: This study shows that it is possible to predict in hereditary predisposition conditions the development of diabetes, and the related dangerous consequences by monitoring two salivary parameters – mucins and malondialdehyde

Prosocial behavior in emergencies: Evidence from blood donors recruitment and retention during the COVID-19 pandemic

The impact of COVID-19 represents a specific challenge for voluntary transfusional systems sustained by the intrinsic motivations of blood donors. In general, health emergencies can stimulate altruistic behaviors. However, in this context, the same prosocial motivations, besides the personal health risks, could foster the adherence to social distancing rules to preserve collective health and, therefore, discourage blood donation activities. In this work, we investigate the consequences of the pandemic shock on the dynamics of new donors exploiting the individual-level longitudinal information contained in administrative data on the Italian region of Tuscany. We compare the change in new donors' recruitment and retention during 2020 with respect to the 2017–2019 period (we observe 9511 individuals), considering donors’ and their municipalities of residence characteristics. Our results show an increment of new donors, with higher proportional growth for older donors. Moreover, we demonstrate that the quality of new donors, as proxied by the frequency of subsequent donations, increased with respect to previous years. Finally, we show that changes in extrinsic motivations, such as the possibility of obtaining a free antibody test or overcoming movement restrictions, cannot explain the documented increase in the number of new donors and in their performance. Therefore, our analyses indicate that the Tuscan voluntary blood donation system was effective in dealing with the challenges posed by the COVID-19 pandemic