SARS-CoV-2 infection leads to Tau pathological signature in neurons (preprint)

Background: The coronavirus disease 19 (COVID-19) has represented an issue for global health since its outbreak in March 2020. It is now evident that the SARS-CoV-2 infection results in a wide range of long-term neurological symptoms and is worryingly associated with the aggravation of Alzheimer's disease. Little is known about the molecular basis of these manifestations. Methods: Several SARS-CoV-2 strain variants were used to infect SH-SY5Y neuroblastoma cells and K18-hACE C57BL/6J mice. The Tau phosphorylation profile and aggregation propensity upon infection were investigated using immunoblot and immunofluorescence on cellular extracts, subcellular fractions, and brain tissue. The viral proteins Spike, Nucleocapsid, and Membrane were overexpressed in SH-SY5Y cells and the direct effect on Tau phosphorylation was checked using immunoblot experiments. Results: Upon infection, Tau is phosphorylated at several pathological epitopes associated with Alzheimer's disease and other tauopathies. Moreover, this event increases Tau's propensity to form insoluble aggregates and alters its subcellular localization. Conclusions: Our data support the evidence that SARS-CoV-2 infection in the Central Nervous System triggers downstream effects altering Tau function, eventually leading to the impairment of neuronal function.

Transcriptional changes of tissue-specific genes in multiple endocrine organs: a study of lethal COVID-19 cases (preprint)

Altered blood hormone and metabolite levels during and post-COVID-19 have been extensively reported. Yet, studies of gene expression at the tissue level that can help identify the causes of endocrine dysfunctions are scarce. We analyzed transcript levels of endocrine-specific genes in five endocrine organs of lethal COVID-19 cases. Overall, 116 autoptic specimens from 77 individuals (50 COVID-19 and 27 uninfected controls) were included. All samples were tested for SARS-CoV-2 genome. Investigated organs included adrenals, pancreas, ovary, thyroid and white adipose tissue (WAT). Transcript levels of 42 endocrine-specific and 3 IFN-stimulated genes (ISGs) were measured and compared between COVID-19 cases (virus-positive and virus-negative in tissue) and uninfected controls. ISG transcript levels were enhanced in tissues positive for SARS-CoV-2. Endocrine-specific genes (e.g., HSD3B2, INS, IAPP, TSHR, FOXE1, LEP, CRYGD) were deregulated in COVID-19 cases in an organ-specific manner. Transcription of organ-specific genes was suppressed in virus-positive specimens of ovary, pancreas and thyroid but enhanced in adrenals. In WAT of COVID-19 cases transcription of ISGs and leptin was enhanced independently of the presence of virus. Our findings suggest that, in COVID-19, endocrine dysfunctions may arise especially when SARS-CoV-2 invades endocrine organs and that transcriptional alterations of endocrine-specific genes may contribute to endocrine manifestations.