A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients

Genome biology, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 14, 2025

Abstract Background The molecular underpinnings of organ dysfunction in severe COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these the context liver function, we perform single-nucleus RNA-seq spatial transcriptomic profiling livers from 17 decedents. Results We identify hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells, a central role pro-fibrotic TGFβ signaling cell–cell communications network. Integrated analysis comparisons healthy controls reveal extensive changes cellular composition states liver, providing underpinning hepatocellular injury, ductular reaction, pathologic vascular expansion, fibrogenesis characteristic cholangiopathy. also observe Kupffer cell proliferation erythrocyte progenitors first time human single-cell atlas. Despite absence clinical acute injury phenotype, endothelial is dramatically impacted COVID-19, concomitantly alterations profibrogenic activation reactive cholangiocytes mesenchymal cells. Conclusions Our atlas provides novel insights into physiology pathology forms foundational resource investigation understanding.

Language: Английский

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Metformin Therapy Changes Gut Microbiota Alpha-Diversity in COVID-19 Patients with Type 2 Diabetes: The Role of SARS-CoV-2 Variants and Antibiotic Treatment

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(6), P. 904 - 904

Published: June 20, 2023

The gut microbiota play a crucial role in maintaining host health and have significant impact on human disease. In this study, we investigated the alpha diversity of COVID-19 patients analyzed variants, antibiotic treatment, type 2 diabetes (T2D), metformin therapy composition diversity. We used culture-based method to analyze calculated alpha-diversity using Shannon H' Simpson 1/D indices. collected clinical data, such as length hospital stay (LoS), C-reactive protein (CRP) levels, neutrophil-to-lymphocyte ratio. found that with T2D had significantly lower than those without T2D. Antibiotic use was associated reduction alpha-diversity, while an increase. did not find differences between Delta Omicron groups. stay, CRP NLR showed weak moderate correlations Our findings suggest diverse may benefit Interventions preserve or restore diversity, avoiding unnecessary use, promoting therapy, incorporating probiotics, improve patient outcomes.

Language: Английский

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Exploring Paxlovid Efficacy in COVID-19 Patients with MAFLD: Insights from a Single-Center Prospective Cohort Study

Viruses, Journal Year: 2024, Volume and Issue: 16(1), P. 112 - 112

Published: Jan. 12, 2024

This study investigates the intricate interplay between Metabolic-associated Fatty Liver Disease (MAFLD) and COVID-19, exploring impact of MAFLD on disease severity, outcomes, efficacy antiviral agent Paxlovid (nirmatrelvir/ritonavir). MAFLD, affecting a quarter global population, emerges as potential risk factor for severe yet underlying pathophysiological mechanisms remain elusive. focuses clinical significance Paxlovid, first orally bioavailable granted Emergency Use Authorization in United States. Notably, outcomes from phase II/III trials exhibit an 88% relative reduction COVID-19-associated hospitalization or mortality among high-risk patients. Despite conflicting data association COVID-19 this research strives to bridge gap by evaluating effectiveness patients with addressing scarcity relevant studies.

Language: Английский

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Genomic insight into COVID-19 severity in MAFLD patients: a single-center prospective cohort study

Frontiers in Genetics, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 4, 2024

This study investigated the influence of single nucleotide polymorphisms (SNPs) in genes associated with interferon pathway (IFNAR2 rs2236757), antiviral response (OAS1 rs10774671, OAS3 rs10735079), and viral entry (ACE2 rs2074192) on COVID-19 severity their association nonalcoholic fatty liver disease (MAFLD). We did not observe a significant between SNPs severity. While IFNAR2 rs2236757 A allele was correlated higher creatinine levels upon admission G lower band neutrophils discharge, these findings require further investigation. The distribution OAS gene (rs10774671 rs10735079) differ MAFLD patients non-MAFLD patients. Our population's ACE2 rs2074192 genotypes alleles differed from that European reference population. Overall, our suggest specific may be major contributors to patient population, highlighting potential role other genetic factors environmental influences.

Language: Английский

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Genetic Predictors of Comorbid Course of COVID-19 and MAFLD: A Comprehensive Analysis

Viruses, Journal Year: 2023, Volume and Issue: 15(8), P. 1724 - 1724

Published: Aug. 12, 2023

Metabolic-associated fatty liver disease (MAFLD) and its potential impact on the severity of COVID-19 have gained significant attention during pandemic. This review aimed to explore genetic determinants associated with MAFLD, previously recognized as non-alcoholic (NAFLD), their influence outcomes. Various polymorphisms, including PNPLA3 (rs738409), GCKR (rs780094), TM6SF2 (rs58542926), LYPLAL1 (rs12137855), been investigated in relation MAFLD susceptibility progression. Genome-wide association studies meta-analyses revealed associations between these variants risk, well effects lipid metabolism, glucose regulation, function. Furthermore, emerging evidence suggests a possible connection MAFLD-associated polymorphisms COVID-19. Studies exploring indicated outcomes shown conflicting results. Some observed protective effect certain against severe COVID-19, while others reported no associations. highlights importance understanding implications for Further research is needed elucidate precise mechanisms linking develop gene profiling tools early prediction If confirmed severity, could aid identification high-risk individuals improving management

Language: Английский

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Modulatory Roles of AHR, FFAR2, FXR, and TGR5 Gene Expression in Metabolic-Associated Fatty Liver Disease and COVID-19 Outcomes

Viruses, Journal Year: 2024, Volume and Issue: 16(6), P. 985 - 985

Published: June 19, 2024

Metabolic-associated fatty liver disease (MAFLD) is a risk factor for severe COVID-19. This study explores the potential influence of gut hormone receptor and immune response gene expression on COVID-19 outcomes in MAFLD patients.

Language: Английский

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Evaluation of the state of small intestinal microbiota, pro- and anti-inflammatory cytokines, short-chain fatty acids in metabolic dysfunction-associated steatotic liver disease in patients with immune response to SARS-CоV-2

GASTROENTEROLOGY, Journal Year: 2025, Volume and Issue: 59(1), P. 37 - 43

Published: March 25, 2025

Background. The intestinal microbiota and its metabolites have a significant impact on the pathophy­siology of liver diseases, it plays an important role in human metabolism, supports mucosal barrier interacts with immune system. COVID-19 epidemic has led to increase number patients Ukraine suffering from metabolic dysfunction-associated steatotic disease (MASLD). One unresolved problems associated MASLD is identification pathogenetic links that affect risk rapid progression development irreversible changes liver. An imbalance trigger for launch pathological reaction purpose: study features content pro- anti-inflammatory cytokines short-chain fatty acids response SARS-CoV-2 depending small bacterial overgrowth (SIBO). Materials methods. included 61 MASLD, 41 men 20 women aged 18 73 years, mean age (46.4 ± 1.5) years. All underwent determination IgG specific SARS-CoV-2, cytokine (IL-6, IL-10, TNF-α) serum by enzyme-linked immunosorbent assay. For diagnosis SIBO, hydrogen breath test (HBT) glucose was performed. Evaluation faeces performed chromatograph using Guohua Zhao method. Results. In 44.3 % SIBO diagnosed. median value IL-6 level significantly exceeded control values 13.7 times (p < 0.001), TNF-α higher 18.5 0.001). group, levels were, accordingly, 2 = 0.01) 3.3 0.004) compared without SIBO. acetic acid (C2) group statistically excee­ded 1.5 0.021). concentration propionic (C3) 1.4 0.003) than those it. At same time, presence decrease butyric (C4) observed 2.2 0.021) Direct correlations were found between (r 0.304, p 0.016); HBT index at 45 min 0.269, 0.041), 0.443, 0.002), 0.400, 0.006). inverse correlation 60 –0.332, 0.040). Conclusions. there production proinflammatory cytokines, contrast increased found. Disturbance microbial composition microbiota, hyperproduction impaired synthesis are distinctive SARS-CoV-2.

Language: Английский

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The global prevalence and impact of steatotic liver disease and viral infections: A systematic review and meta-analysis

Hepatology Communications, Journal Year: 2025, Volume and Issue: 9(5)

Published: April 14, 2025

Background: Steatotic liver disease (SLD) affects ~30% of adults worldwide. The global population is continuously threatened by epidemic and endemic viral diseases. This study aims to thoroughly examine the interaction between SLD major Methods: We systematically searched databases from inception April 2, 2024, for observational studies recording viral-infected adult patients with eligible data on presence hepatic steatosis. Results: Six hundred thirty-six were included in analysis prevalence. Among monoinfections, highest prevalence was observed those infected HCV at 49% (95% CI: 47%–51%), followed SARS-CoV-2 (39%, 95% CI [34%–44%]), HIV [33%–44%]), HBV (36%, [32%–40%]). Additionally, co-infections, such as HCV-HIV HBV-HCV, exhibit even higher steatohepatitis particularly high HIV-infected (24%, 17%–30%) HCV-infected (18%, 13%–24%) populations. co-existence infections associated not only progression but also more severe outcomes poorer responses antiviral treatment. combination cardiometabolic risk factors viral-associated host contributes Conclusions: highly prevalent populations, reciprocal interactions diseases exacerbate both conditions, leading patient general.

Language: Английский

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Modulatory Roles of AHR, FFAR2, FXR, and TGR5 Gene Expression in MAFLD and COVID-19 Outcomes

Published: May 13, 2024

Metabolic-associated fatty liver disease (MAFLD) is a risk factor for severe COVID-19. This study explores the potential influence of gut hormone receptor and immune response gene expression on COVID-19 outcomes in MAFLD patients. Methods: We investigated levels AHR, FFAR2, FXR, TGR5 patients with compared to controls. examined associations between clinical outcomes. Results: displayed altered AHR expression, potentially impacting recovery. Downregulated correlated increased coagulation parameters. Elevated FFAR2 linked specific cell populations hospital stay duration. Significantly lower FXR was observed both Conclusion: Our findings suggest modulatory roles MAFLD.

Language: Английский

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Unlocking the gut-liver axis: microbial contributions to the pathogenesis of metabolic-associated fatty liver disease

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: April 25, 2025

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a complex metabolic disorder characterized by hepatic lipid accumulation and subsequent inflammation. This condition closely linked to syndrome obesity, with its prevalence rising due sedentary lifestyles high-calorie diets. The pathogenesis of MAFLD involves multiple factors, including insulin resistance, lipotoxicity, oxidative stress, inflammatory responses. gut microbiota plays crucial role in development, dysbiosis contributing inflammation through various mechanisms, such as enhanced intestinal permeability the translocation bacterial products like lipopolysaccharide (LPS). Microbial metabolites, short-chain acids (SCFAs) bile acids, influence function immune responses, potential implications for progression. Specific microbiome signatures have been identified patients, offering diagnostic therapeutic targets. Moreover, gut-derived toxins, endotoxins, lipopolysaccharides, trimethylamine-N-oxide significantly damage inflammation, highlighting interplay between health. review comprehensively examines MAFLD, focusing on underlying pathogenic biomarkers, emerging microbiome-targeted strategies management.

Language: Английский

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