GDF15 and ACE2 stratify COVID-19 patients according to severity while ACE2 mutations increase infection susceptibility

Coronavirus disease 19 (COVID-19) is a persistent global pandemic with a very heterogeneous disease presentation ranging from a mild disease to dismal prognosis. Early detection of sensitivity and severity of COVID-19 is essential for the development of new treatments. In the present study, we measured the levels of circulating growth differentiation factor 15 (GDF15) and angiotensin-converting enzyme 2 (ACE2) in plasma of severity-stratified COVID-19 patients and uninfected control patients and characterized the in vitro effects and cohort frequency of ACE2 SNPs. Our results show that while circulating GDF15 and ACE2 stratify COVID-19 patients according to disease severity, ACE2 missense SNPs constitute a risk factor linked to infection susceptibility

Host factor PLAC8 is required for pancreas infection by SARS-CoV-2

Although mounting evidence demonstrated that pancreas is infected by SARS-CoV-2 the severity and pathophysiology of pancreatic COVID-19 disease are still unclear. Here we investigated the consequences of SARS-CoV-2 infection of the pancreas and the role of Placenta-associated protein-8 (PLAC8). Our data showed pancreatic damage in patients who died from COVID-19. Notably, circulating pancreatic enzymes stratified patients according to COVID-19 severity and outcome. PLAC8 expression was associated with SARS-CoV-2 infection in postmortem analysis of COVID-19 patients and functional assays demonstrated the requirement of PLAC8 in SARS-CoV-2 pancreatic infection. Full SARS-CoV-2 infectious virus revealed a requirement of PLAC8 for efficient viral infection of pancreatic cell lines. Finally, we observed colocalization of PLAC8 and SARS-CoV-2 in the pancreas of deceased patients. In conclusion, our data confirm the human pancreas as a SARS-CoV-2 target and demonstrate the requirement of PLAC8 for SARS-CoV-2 pancreatic infection thereby opening new target opportunities for COVID-19-associated pancreatic pathogenesis.N

Organoids: An Emerging Tool to Study Aging Signature across Human Tissues. Modeling Aging with Patient-Derived Organoids

The biology of aging is focused on the identification of novel pathways that regulate the underlying processes of aging to develop interventions aimed at delaying the onset and progression of chronic diseases to extend lifespan. However, the research on the aging field has been conducted mainly in animal models, yeast, Caenorhabditis elegans, and cell cultures. Thus, it is unclear to what extent this knowledge is transferable to humans since they might not reflect the complexity of aging in people. An organoid culture is an in vitro 3D cell-culture technology that reproduces the physiological and cellular composition of the tissues and/or organs. This technology is being used in the cancer field to predict the response of a patient-derived tumor to a certain drug or treatment serving as patient stratification and drug-guidance approaches. Modeling aging with patient-derived organoids has a tremendous potential as a preclinical model tool to discover new biomarkers of aging, to predict adverse outcomes during aging, and to design personalized approaches for the prevention and treatment of aging-related diseases and geriatric syndromes. This could represent a novel approach to study chronological and/or biological aging, paving the way to personalized interventions targeting the biology of aging