Bioinformatics and systems biology approach to identify the pathogenetic link of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Lv, Yongbiao; Zhang, Tian; Cai, Junxiang; Huang, Chushuan; Zhan, Shaofeng; Li, Jianbo

doi:10.3389/fimmu.2022.952987

Cited by 15 publications

(9 citation statements)

References 112 publications

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“…Transcription factors (TFs) are proteins that can bind to specific DNA sequences and regulate gene expression ( 43 ). MicroRNAs (miRNAs) are a class of endogenous short non-coding RNAs that mediate the degradation of target mRNAs or repress translation ( 44 ).…”

Section: Methodsmentioning

confidence: 99%

Transcriptomic analysis reveals shared gene signatures and molecular mechanisms between obesity and periodontitis

Cai

Zuo

et al. 2023

Front. Immunol.

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BackgroundBoth obesity (OB) and periodontitis (PD) are chronic non-communicable diseases, and numerous epidemiological studies have demonstrated the association between these two diseases. However, the molecular mechanisms that could explain the association between OB and PD are largely unclear. This study aims to investigate the common gene signatures and biological pathways in OB and PD through bioinformatics analysis of publicly available transcriptome datasets.MethodsThe RNA expression profile datasets of OB (GSE104815) and PD (GSE106090) were used as training data, and GSE152991 and GSE16134 as validation data. After screening for differentially expressed genes (DEGs) shared by OB and PD, gene enrichment analysis, protein-protein interaction (PPI) network construction, GeneMANIA analysis, immune infiltration analysis and gene set enrichment analysis (GSEA) were performed. In addition, receiver operating characteristic (ROC) curves were used to assess the predictive accuracy of the hub gene. Finally, we constructed the hub gene-associated TF-miRNA-mRNA regulatory network.ResultsWe identified a total of 147 DEGs shared by OB and PD (38 down-regulated and 109 up-regulated). Functional analysis showed that these genes were mainly enriched in immune-related pathways such as B cell receptor signalling, leukocyte migration and cellular defence responses. 14 hub genes (FGR, MNDA, NCF2, FYB1, EVI2B, LY86, IGSF6, CTSS, CXCR4, LCK, FCN1, CXCL2, P2RY13, MMP7) showed high sensitivity and specificity in the ROC curve analysis. The results of immune infiltration analysis showed that immune cells such as macrophages, activated CD4 T cells and immune B cells were present at high infiltration levels in both OB and PD samples.The results of GeneMANIA analysis and GSEA analysis suggested that five key genes (FGR, LCK, FYB1, LY86 and P2RY13) may be strongly associated with macrophages. Finally, we constructed a TF-miRNA-mRNA regulatory network consisting of 233 transcription factors (TFs), 8 miRNAs and 14 mRNAs based on the validated information obtained from the database.ConclusionsFive key genes (FGR, LCK, FYB1, LY86, P2RY13) may be important biomarkers of OB and PD. These genes may play an important role in the pathogenesis of OB and PD by affecting macrophage activity and participating in immune regulation and inflammatory responses.

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Section: Methodsmentioning

confidence: 99%

Transcriptomic analysis reveals shared gene signatures and molecular mechanisms between obesity and periodontitis

Cai

Zuo

et al. 2023

Front. Immunol.

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“…Although there are no studies directly proving that acute COVID-19 triggers ME/CFS, several studies have identified multiple overlapping or similar symptoms between long COVID and ME/CFS [ 127 ]. COVID-19 also greatly increases the number of patients with ME/CFS [ 128 ], and bioinformatics analysis has identified a common network of genetic interactions between the two [ 129 ]. According to the diagnostic criteria for ME/CFS, the overall prevalence of ME/CFS was as high as 43% among patients with long COVID, with fatigue, malaise on exertion, and insomnia representing the main symptoms [ 130 ].…”

Section: Therapeutic Potential Of Naringin and Naringenin In Long Covidmentioning

confidence: 99%

Potential Beneficial Effects of Naringin and Naringenin on Long COVID—A Review of the Literature

Liu,

Zhong,

et al. 2024

Microorganisms

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Coronavirus disease 2019 (COVID-19) caused a severe epidemic due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have found that patients do not completely recover from acute infections, but instead, suffer from a variety of post-acute sequelae of SARS-CoV-2 infection, known as long COVID. The effects of long COVID can be far-reaching, with a duration of up to six months and a range of symptoms such as cognitive dysfunction, immune dysregulation, microbiota dysbiosis, myalgic encephalomyelitis/chronic fatigue syndrome, myocarditis, pulmonary fibrosis, cough, diabetes, pain, reproductive dysfunction, and thrombus formation. However, recent studies have shown that naringenin and naringin have palliative effects on various COVID-19 sequelae. Flavonoids such as naringin and naringenin, commonly found in fruits and vegetables, have various positive effects, including reducing inflammation, preventing viral infections, and providing antioxidants. This article discusses the molecular mechanisms and clinical effects of naringin and naringenin on treating the above diseases. It proposes them as potential drugs for the treatment of long COVID, and it can be inferred that naringin and naringenin exhibit potential as extended long COVID medications, in the future likely serving as nutraceuticals or clinical supplements for the comprehensive alleviation of the various manifestations of COVID-19 complications.

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“… 89 , 98 The widespread inflammatory response triggered by SARS-CoV-2 infection has been reported in patients with varying degrees of illness severity, 80 , 99 which could occur in the nervous system and contribute to neuropsychiatric symptoms. 80 , 83 The interaction networks of ME/CFS and long COVID, including inflammatory cytokines comprising interleukin (IL)-6 and IL-1B, common genes, and microRNAs, have recently been depicted, 100 revealing the potential mechanism of ME/CFS in the occurrence of long COVID and further emphasizing the significance of the inflammatory response. Meanwhile, the dysregulation of endothelin-1 has been found in long COVID patients and cases presenting exertion intolerance and persistent fatigue, suggesting the emergence of endothelial dysfunction and its effect on ME/CFS.…”

Section: Symptoms and Possible Mechanismsmentioning

confidence: 99%

The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID

Li,

Zhou,

et al. 2023

Sig Transduct Target Ther

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There have been hundreds of millions of cases of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the growing population of recovered patients, it is crucial to understand the long-term consequences of the disease and management strategies. Although COVID-19 was initially considered an acute respiratory illness, recent evidence suggests that manifestations including but not limited to those of the cardiovascular, respiratory, neuropsychiatric, gastrointestinal, reproductive, and musculoskeletal systems may persist long after the acute phase. These persistent manifestations, also referred to as long COVID, could impact all patients with COVID-19 across the full spectrum of illness severity. Herein, we comprehensively review the current literature on long COVID, highlighting its epidemiological understanding, the impact of vaccinations, organ-specific sequelae, pathophysiological mechanisms, and multidisciplinary management strategies. In addition, the impact of psychological and psychosomatic factors is also underscored. Despite these crucial findings on long COVID, the current diagnostic and therapeutic strategies based on previous experience and pilot studies remain inadequate, and well-designed clinical trials should be prioritized to validate existing hypotheses. Thus, we propose the primary challenges concerning biological knowledge gaps and efficient remedies as well as discuss the corresponding recommendations.

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Bioinformatics and systems biology approach to identify the pathogenetic link of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Cited by 15 publications

References 112 publications

Transcriptomic analysis reveals shared gene signatures and molecular mechanisms between obesity and periodontitis

Transcriptomic analysis reveals shared gene signatures and molecular mechanisms between obesity and periodontitis

Potential Beneficial Effects of Naringin and Naringenin on Long COVID—A Review of the Literature

The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID

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