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Insight into molecular mechanisms underlying hepatic dysfunction in severe COVID-19 patients using systems biology

World Journal of Gastroenterology 2021年第21期27卷 2850-2870页

作者： Sarah Musa Hammoudeh Arabella Musa Hammoudeh poorna manasa bhamidimarri Bassam Mahboub Rabih Halwani Qutayba Hamid Mohamed Rahmani Rifat Hamoudi Sharjah Institute for Medical Research College of MedicineUniversity of SharjahSharjah 27272United Arab Emirates College of Medicine University of SharjahSharjah 27272United Arab Emirates General Surgery Department Tawam HospitalSEHAAl-Ain 15258United Arab Emirates Rashid Hospital 315 Umm Hurair SecondDubai Health AuthorityDubai 4545United Arab Emirates Meakins-Christie Laboratories McGill UniversityQuebec H4A 3J1MontrealCanada Division of Surgery and Interventional Science University College LondonLondon W1W 7TYUnited Kingdom

BACKGROUND The coronavirus disease 2019(COVID-19),a pandemic contributing to more than 105 million cases and more than 2.3 million deaths worldwide,was described to be frequently accompanied by extrapulmonary manifestations,including liver *** dysfunction and elevated liver enzymes were observed in about 53%of COVID-19 *** To gain insight into transcriptional abnormalities in liver tissue of severe COVID-19 patients that may result in liver *** The transcriptome of liver autopsy samples from severe COVID-19 patients against those of non-COVID donors was *** expressed genes were identified from normalized RNA-seq data and analyzed for the enrichment of functional clusters and *** differentially expressed genes were then compared against the genetic signatures of liver diseases including cirrhosis,fibrosis,non-alcoholic fatty liver disease(NAFLD),and hepatitis A/B/*** expression of some differentially expressed genes was assessed in the blood samples of severe COVID-19 patients with liver dysfunction using *** Analysis of the differential transcriptome of the liver tissue of severe COVID-19 patients revealed a significant upregulation of transcripts implicated in tissue remodeling including G-coupled protein receptors family genes,DNAJB1,IGF2,EGFR,and ***,the differential transcriptome of severe COVID-19 liver tissues substantially overlapped with the disease signature of liver diseases characterized with pathological tissue remodeling(liver cirrhosis,Fibrosis,NAFLD,and hepatitis A/B/C).Moreover,we observed a significant suppression of transcripts implicated in metabolic pathways as well as mitochondrial function,including cytochrome P450 family members,ACAD11,CIDEB,GNMT,and ***,drug and xenobiotics metabolism pathways are significantly suppressed suggesting a decrease in liver detoxification *** correspondence with the RNA-seq data analysis,we observ

关键词： COVID-19 Hepatic dysfunction Tissue remodeling Metabolic pathways Drug metabolism Hepatic detoxification

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