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

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.Liver dysfunction and elevated liver enzymes were observed in about 53%of COVID-19 patients.AIM To gain insight into transcriptional abnormalities in liver tissue of severe COVID-19 patients that may result in liver dysfunction.METHODS The transcriptome of liver autopsy samples from severe COVID-19 patients against those of non-COVID donors was analyzed.Differentially expressed genes were identified from normalized RNA-seq data and analyzed for the enrichment of functional clusters and pathways.The 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/C.Gene expression of some differentially expressed genes was assessed in the blood samples of severe COVID-19 patients with liver dysfunction using qRT-PCR.RESULTS 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 HDGF.Concordantly,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 GPAM.Consequently,drug and xenobiotics metabolism pathways are significantly suppressed suggesting a decrease in liver detoxification capacity.In correspondence with the RNA-seq data analysis,we observed a significant upregulation of DNAJB1 and HSP90AB1 as well as significant downregulation of CYP39A1 in the blood plasma of severe COVID-19 patients with liver dysfunction.CONCLUSION Severe COVID-19 patients appear to experience significant transcriptional shift that may ensue tissue remodeling,mitochondrial dysfunction and lower hepatic detoxification resulting in the clinically observed liver dysfunction.

Sleep breathing disorders in female population of Dubai, UAE

PURPOSE: United Arab Emirates (UAE) is part of the GCC countries and ranks 18 on 2007 WHO list of the fattest countries with 68.3% of its citizens with an unhealthy weight. The WHO data in 2008 state that the prevalence of overweight in UAE is 71%, while it is 61% in the UK, 54% in Germany, and 45% in France. The increasing overweight and obesity in the UAE are closely related to high social-economic development. Accordingly, the medical authority has observed that the rates of hypertension and diabetes mellitus type 2 appear to be one of the highest rates worldwide. We presume that the increase prevalence of obesity in the UAE would be linked to the increase in prevalence of obstructive sleep apnea syndrome (OSAS). The purpose of this study is to estimate the prevalence of symptoms and risk of OSAS in women followed up in the primary health care (PHC) setting in Dubai and the relationship between obesity and sleep apnea in females in the UAE. DESIGN: Prospective observational community-based survey. SETTING: 20 primary health centers in Dubai. PARTICI-PANTS: Consecutive female patients who were older than 14 years, regardless of the reason of their visit. METHODS: In this prospective survey, trained medical nurse administered the Berlin Questionnaire (which includes questions about self-reported snoring, witnessed apneas, daytime sleepiness, hypertension, and obesity) to a consecutive random sample of female patients in the age group older than 14 years, attending the PHC center in Dubai Health Authority, Dubai, UAE, from September 2011 to March 2012. Based on the questionnaire, individuals were classified into high-risk and low-risk groups for OSAS. RESULTS: Based on the responses and measurement of the Berlin Questionnaire of 704 female subjects studied, 137 respondents met the criteria for the high-risk scoring. This gives a prevalence rate of 19.5% while the remainders of the participants were classified as low risk. The overall mean age of the high risk for OSAS female respondents was 39.95 ± 11.73 years. The highest prevalence was noticed between age group 51 to 60 years. 70% of the high risk group patients had Body Mass Index (BMI) ≥30 kg/m2 and nearly 75% of the low risk group had BMI 2 and the Mean BMI was 33.59 ± 6.44 kg/m2. CONCLUSIONS: One in five women in Dubai, UAE is at high risk of having OSAS. Awareness by the primary care medical community about this disorder in females should be increased so that the patients would benefit from proper evaluation and treatment of OSAS.