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

Self Cite

Coronavirus disease (COVID-19) and its outcomes remain one of the most challenging problems today. COVID-19 in children could be asymptomatic, but can result in a fatal outcome; therefore, predictions of the disease severity are important. The goal was to investigate the human genetic factors that could be associated with COVID-19 severity in children. Single-nucleotide polymorphisms of the following genes were studied: ACE2 (rs2074192), IFNAR2 (rs2236757), TYK2 (rs2304256), OAS1 (rs10774671), OAS3 (rs10735079), CD40 (rs4813003), FCGR2A (rs1801274) and CASP3 (rs113420705). In the case–control study were 30 children with mild or moderate course of the disease; 30 with severe COVID-19 symptoms and multisystem inflammatory syndrome in children (MIS-C) and 15 who were healthy, and who did not have SARS-CoV-2 (PCR negative, Ig G negative). The study revealed that ACE2 rs2074192 (allele T), IFNAR2 rs2236757 (allele A), OAS1 rs10774671 (allele A), CD40 rs4813003 (allele C), CASP3 rs113420705 (allele C) and male sex contribute to severe COVID-19 course and MIS-C in 85.6% of cases. The World Health Organization reported that new SARS-CoV-2 variants may cause previously unseen symptoms in children. Although the study has limitations due to cohort size, the findings can help provide a better understanding of SARS-CoV-2 infection and proactive pediatric patient management.

Section: Discussionmentioning

confidence: 99%

The Relationship between COVID-19 Severity in Children and Immunoregulatory Gene Polymorphism

Kozak,

Pavlyshyn,

Kamyshnyi

et al. 2023

Self Cite

“…Hence, existing literature posits that individuals with MAFLD may be at augmented risk of experiencing severe COVID-19 [ 1 , 11 , 34 , 35 , 36 ], necessitating intensive care and supervision, requiring ICU-level supervision and care [ 1 , 34 ]. Nevertheless, the body of evidence on this association is not devoid of conflicting data.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous genetic polymorphisms, such as PNPLA3 (rs738409), GCKR (rs780094), TM6SF2 (rs58542926), and LYPLAL1 (rs12137855), have undergone scrutiny concerning their association with MAFLD susceptibility and progression. Certain studies propose a plausible correlation between these MAFLD-associated polymorphisms and the severity of COVID-19 [ 35 ]. It is imperative to explore the potential synergistic effects of these genetic polymorphisms, thereby contributing to a comprehensive understanding of the intricate interplay between MAFLD susceptibility and the outcomes of COVID-19.…”

Section: Discussionmentioning

confidence: 99%

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

Buchynskyi,

Oksenych,

Kamyshna

et al. 2024

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

“…Several studies have specifically highlighted Metabolic Associated Fatty Liver Disease (MAFLD) as a potential independent risk factor for both SARS-CoV-2 acquisition and hospitalization during COVID-19 illness, even after controlling for other aspects of metabolic syndrome [ 10 , 11 , 12 ]. Furthermore, research suggests that MAFLD may contribute to altered gene expression patterns, potentially influencing the course of COVID-19 [ 13 , 14 ]. To elucidate the intricate interplay between these conditions, further investigation into the differential gene expression patterns associated with co-occurrence of MAFLD and COVID-19 is warranted [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

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

Buchynskyi,

Oksenych,

Kamyshna

et al. 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 gene expression levels of AHR, FFAR2, FXR, and TGR5 in patients with MAFLD and COVID-19 compared to controls. We examined associations between gene expression and clinical outcomes. Results: COVID-19 patients displayed altered AHR expression, potentially impacting immune response and recovery. Downregulated AHR in patients with MAFLD correlated with increased coagulation parameters. Elevated FFAR2 expression in patients with MAFLD was linked to specific immune cell populations and hospital stay duration. A significantly lower FXR expression was observed in both MAFLD and severe COVID-19. Conclusion: Our findings suggest potential modulatory roles for AHR, FFAR2, and FXR in COVID-19 and MAFLD.