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American Journal of Respiratory and Critical Care Medicine ; 205:1, 2022.
Article in English | English Web of Science | ID: covidwho-1880162
Kidney International Reports ; 6(4):S221, 2021.
Article in English | EMBASE | ID: covidwho-1198727


Introduction: The ongoing SARS-COV-2 pandemic hit the world’s population since the first trimester of 2020. Since the beginning it has been clear that the elderly and chronic patients were at greater risk ofmorbidity and mortality. The aim of the study was to monitor the spread and outcomes amongpatients in kidney replacement therapy treated in Nephrology-Dialysis units in Piedmont and Valled’Aosta Regions, North-West Italy. Methods: A web platform accessible by Dialysis coordinators across the first and second wave of the pandemic is still being used to collect and regularly update demographic and clinical data of patients. We present preliminary results on cumulative incidence, risk estimates and measures of association. Data were analyzed using SPSS version 19 and Wizard 1.9.47 for Mac. Results: An overall of 599 cases has been monitored since March 2020 till November 2020. The cumulative incidence is 10% compared to 3,3% of the general population. A higher cumulative incidence has been observed among Hemodialysis patients (14%), while in peritoneal dialysis patients and transplant receivers’ sub-groups it is 5,3% and 6,6%, respectively. Compared to the general population, among dialysis patients, cumulative incidence grew at a slower rate in the first than in the second wave of pandemic (incidence rate ratio of 1,65 for patients compared to 5,9 for the rest of the population). A higher fatality risk is observed among dialysis patients and transplant receivers (17% and11%, respectively) compared to that of the general population of 3,7%. Fatality is associated with age and cardiovascular diseases in both groups. Conclusions: The study of an overall population of 599 showed a higher susceptibility to SARS-COV-2 infection and worse outcomes compared to the general population. We observed increased risks for hemodialysis patients, who are older on average and more exposed to in-hospital infections. No conflict of interest

Hepatology ; 72(1 SUPPL):278A, 2020.
Article in English | EMBASE | ID: covidwho-986075


Background: COVID-19 was declared a pandemic by the World Health Organization, caused by severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2) Respiratory failure is the most common mortality outcome in COVID-19 patients, yet serious and even fatal manifestations are seen across multiple organ systems Emerging clinical data from our own hospital revealed a high prevalence of initial presentations with GI manifestations Almost one third of patients presenting to our hospital reported at least one gastrointestinal manifestation including nausea, vomiting, diarrhea, or abdominal pain 62% of patients presented with biochemical evidence of liver injury Moreover, the presence of liver injury on presentation was associated with a significantly higher risk of ICU admission and death As this is a new and novel clinical entity, robust in vitro models that phenocopy SARS-CoV-2 infection and human COVID-19 disease are limited Current in vitro (e g Vero cells) and in vivo models (mouse models engineered with ACE2) are so distinct from human infection that they may not capture key components of viral infection or virus-host interactions Therefore, the development of robust human models of COVID-19 infection will be essential for the study of SARS-Cov-2 viral infection and to identify robust SARS-CoV-2 therapeutics Methods: Human pluripotent stem cells (hPSCs), including human embryonic stem cells hESCs) and induced pluripotent stem cells (hiPSCs), can be used to derive functional human cells/tissues/organoids for modeling human disease and drug discovery, including for infectious diseases Here we leveraged several stem cell platforms (e g endodermal lineages including hepatocyte and cholangiocyte) along with primary human hepatocytes and cholangiocyte organoid systems to study SARS-CoV-2 infection SARS-CoV-2 pseudoparticles were used to study SARS-CoV-2 viral entry SARS-CoV-2 (USA-WA1/2020) was used to validate viral infection and to study cellular response Autopsy liver samples from COVID-19 patients were obtained and compared to SARS-CoV-2 infected liver models Results: Adult hepatocyte and cholangiocyte organoids along with PSC derived hepatocytes and cholangiocytes are Permissive to SARS-CoV-2 virus infection and show similar transcriptome changes and chemokine responses for SARSCoV- 2 infection as seen in autopsy samples from COVID-19 Patients Conclusion: We report here the development of robust models of SARS-CoV-2 infection in primary and PSC derived hepatocyte and cholangiocytes which phenocopy COVID-19 hepatic disease These disease-relevant human cell/organoid-based platforms can be directly applied for drug screening and the evaluation of prospective antiviral therapeutics as well be used to delineate molecular mechanisms underlying COVID-19 disease.