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Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Long COVID. Core disease mechanisms, molecular and cellular pathways, invo...

2026-05-08
Asta MONDO:0100233 Model: Asta Scientific Corpus Retrieval 20 citations

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Long COVID. Core disease mechanisms, molecular and cellular pathways, invo...

This report is retrieval-only and is generated directly from Asta results.

  • Papers retrieved: 20
  • Snippets retrieved: 20

Relevant Papers

[1] Advances in Understanding Long COVID: Pathophysiological Mechanisms and the Role of Omics Technologies in Biomarker Identification

  • Authors: M. D. da Silva, Thamires Santos da Silva, C. G. Mendes, Maria Carolina Miglino Valbão, Abraham K. Badu-Tawiah et al.
  • Year: 2025
  • Venue: Molecular Diagnosis & Therapy
  • URL: https://www.semanticscholar.org/paper/95786e6f2370d6f34db44ab65d09f11ba45d11c5
  • DOI: 10.1007/s40291-025-00792-8
  • PMID: 40531392
  • PMCID: 12436531
  • Citations: 5
  • Summary: Recent advances in understanding long COVID are discussed, addressing its mechanisms, risk factors, the impact of viral variants, and the role of vaccination, with an emphasis on the importance of omics technologies in elucidating this condition.
  • Evidence snippets:
  • Snippet 1 (score: 0.528) > Long COVID remains a multifaceted condition, impacting multiple organ systems and manifesting through a wide range of symptoms that span from mild, flu-like manifestations to severe complications involving cardiovascular and neurological systems. Its pathogenesis involves complex interactions across numerous cellular and molecular pathways, highlighting its unique impact on physiological processes. As a result, personalized therapeutic interventions, such as immune response modulation, the restoration of cellular metabolism, and therapies targeting mitochondrial function, are emerging as potential strategies to address the diverse clinical manifestations of long COVID. The condition's multifaceted nature necessitates an interdisciplinary approach, integrating clinical, immunological, and molecular assessments alongside consideration of genetic predisposition, preexisting conditions, and the interplay between viral persistence and the host immune response. The role of omics technologies-particularly proteomics, lipidomics, and metabolomics-has been central to advancing our understanding of long COVID. These high-throughput techniques provide invaluable insights into the molecular alterations associated with the condition, facilitating the identification of biomarkers to predict disease severity, monitor progression, and inform treatment strategies. Integration with advanced computational methods enables a more comprehensive view of these molecular dynamics over time. Longitudinal studies are particularly valuable for capturing biomarker evolution from the acute phase through recovery and for assessing the effects of interventions such as rehabilitation programs or emerging therapies. > However, significant challenges remain. The studies often face limited sample sizes and must contend with the profound heterogeneity of long COVID-both in symptom presentation and in underlying biological mechanisms. The wide range of manifestations, including respiratory, neurological, and metabolic, suggests multiple distinct pathophysiological pathways. This diversity complicates data interpretation, as integrating findings across heterogeneous populations may dilute individual-specific signals or obscure relevant associations. Additionally, discrepancies across studies frequently stem from variations in design, cohort characteristics, and symptom classification, highlighting the urgent need for standardized protocols and stratified analyses to disentangle the complex biology of long COVID, particularly given the heterogeneity of symptoms, patient populations, and potential underlying mechanisms.

[2] Beyond dexamethasone, emerging immuno‐thrombotic therapies for COVID‐19

  • Authors: M. Jensen, M. George, D. Gilroy, R. Sofat
  • Year: 2020
  • Venue: British Journal of Clinical Pharmacology
  • URL: https://www.semanticscholar.org/paper/abe737ee4f8371568804e4bc37a89d81d53f50e9
  • DOI: 10.1111/bcp.14540
  • PMID: 32881064
  • Citations: 7
  • Summary: The pathophysiological mechanisms underpinning these cascades are reviewed with clinical correlates and the current therapeutic approaches being investigated to formulating rationale therapeutic approaches beyond the use of dexamethasone.
  • Evidence snippets:
  • Snippet 1 (score: 0.519) > By reviewing what is known about the clinical and molecular pathophysiology of COVID-19 we have outlined a framework to understand existing therapeutic endeavours. Rational efforts to repurpose existing drugs can be understood in the context of the molecular pathways outlined-from upstream targets (entry via ACE2 or viral replication) to downstream targets (modulating the hyperinflammatory state and/or the coagulopathy). We therefore propose that 1 therapeutic approach could be viral clearance by either small molecular entities or preventative approaches when vaccines are available. However, advanced cases where immunological and thrombotic complications are present may require a combination approach, targeting both viral clearance and adjunctive treatment to address the key complications of serious infection (hyperinflammation and coagulopathy). The benefit of antivirals as adjunctive treatments in severe COVID-19 requires a better understanding of the degree to which viral persistence contributes to deterioration, requiring further studies exploring the relationship between viral RNA load kinetics and disease severity. > To move forward, it is essential to analyse the clinical phenotypes by collecting data on patient demographics, comorbidities, medication history, disease severity, and progression towards surrogate and clinical endpoints. We also require detailed laboratory data, including virology parameters (viral load, acute and convalescent serology) and inflammatory markers (including cytokine profiling), ideally with both real-time systemic and intrapulmonary monitoring. Genome-wide association studies, RNA and proteomic analyses will be crucial in evaluating the pathogenic mechanism behind intrinsic risk factors (for example sex and ethnicity), and approaches including Mendelian randomisation may steer towards causal pathways prioritising drugs for repurposing. Once the backlog of coronial autopsies is processed, research autopsies on COVID-19 positive patients must be prioritised. > The histology from postmortem studies, as well as the cytopathology from bronchoalveolar lavage, will be crucial in elucidating the mechanisms of mortality. Across all of these data domains, large cohorts will need to be analysed before conclusions can be drawn. To better understand the molecular pathways at play, efforts should also be made to elucidate the

[3] Low‐Dose naltrexone restored TRPM3 ion channel function in natural killer cells from long COVID patients

  • Authors: E. Sasso, N. Eaton-Fitch, Peter Smith, Katsuhiko Muraki, Sonya Marshall-Gradisnik
  • Year: 2025
  • Venue: Frontiers in Molecular Biosciences
  • URL: https://www.semanticscholar.org/paper/2eade41b8d0fea9af2ca2d1f5a5dcf4f16e9659f
  • DOI: 10.3389/fmolb.2025.1582967
  • PMID: 40458265
  • PMCID: 12127304
  • Citations: 2
  • Summary: The findings support LDN as a potentially beneficial treatment for long COVID patients by restoring TRPM3 ion channel function and reestablishing adequate Ca2+ influx necessary for homeostatic cellular processes.
  • Evidence snippets:
  • Snippet 1 (score: 0.490) > Similarly, studies have demonstrated that immune dysregulation is a key feature in the pathophysiology of long COVID, with underlying mechanisms varying according to the long COVID phenotype, the severity of the acute infection, and the tissues or organs involved (Gomes et al., 2023;Sanchez-Menendez et al., 2024;Yin et al., 2024;Mohandas et al., 2023;Altmann et al., 2023). A recent publication identified transcriptome alteration in long COVID patients, with fifteen upregulated and Abbreviations: BMI, body mass index; Ca 2+ , calcium; EDTA, ethylenediaminetetraacetic acid; FBC, Full Blood Count; GPCR, guanine nucleotide-binding protein-coupled receptors; HC, healthy controls; IL, interleukin; LDN, low-dose naltrexone; ME/CFS, myalgic encephalomyelitis/chronic fatigue syndrome; NAD+, nicotinamide adenine dinucleotide; NCNED, National Centre for Neuroimmunology and Emerging Diseases; NK, natural killer; NTX, naltrexone; PBMC, peripheral blood mononuclear cells; PregS, pregnenolone sulfate; QoL, quality of life; SARS-CoV-2, respiratory syndrome coronavirus 2; SD, standard derivation; SF-36, 36-item Short-Form Health Survey; SPSS, Statistical Package for the Social Sciences; TGF, transforming growth factor; TLR4, Toll-like receptor 4; TRPM3, Transient Receptor Potential Melastatin 3; WHO, World Health Organization; WHODAS, World Health Organization Disability Assessment Schedule. > fourteen downregulated genes, suggesting abnormalities in the expression of genes involved in antigen presentation, cytokine signaling, and immune cell activation (Eaton-Fitch et al., 2024). Data from a plasma protein investigation indicated that NK cells in individuals with long COVID exhibit a shift from an activated to a resting phenotype, based on reduced expression of CC-chemokine receptor 7 markers (Iosef et al., 2023).

[4] Pathophysiological Mechanisms in Long COVID: A Mixed Method Systematic Review

  • Authors: N. Diar Bakerly, Nikki Smith, Julie L Darbyshire, Joseph Kwon, Emily Bullock et al.
  • Year: 2024
  • Venue: International Journal of Environmental Research and Public Health
  • URL: https://www.semanticscholar.org/paper/245f9fc9802945b8e70d3baa3b7d6ffc060b8885
  • DOI: 10.3390/ijerph21040473
  • PMID: 38673384
  • PMCID: 11050596
  • Citations: 18
  • Summary: LC is a complex condition affecting multiple organs with diverse clinical presentations (or traits) underpinned by multiple pathophysiological mechanisms, and future research must include understanding the response to intervention based on these mechanism-based traits.
  • Evidence snippets:
  • Snippet 1 (score: 0.466) > Pathophysiological Mechanisms in Long COVID: A Mixed Method Systematic Review

[5] Prediction of severe adverse events, modes of action and drug treatments for COVID-19’s complications

  • Authors: C. Astore, Hongyi Zhou, Joshy Jacob, J. Skolnick
  • Year: 2021
  • Venue: Scientific Reports
  • URL: https://www.semanticscholar.org/paper/58831d6f4f1f144c67594e2455065f0f935183a4
  • DOI: 10.1038/s41598-021-00368-6
  • PMID: 34675303
  • PMCID: 8531388
  • Citations: 4
  • Summary: A novel AI methodology MOATAI-VIR, which predicts disease-protein-pathway relationships and repurposed FDA-approved drugs to treat COVID-19’s clinical manifestations was developed, and 24/26 of the major clinical manifestations are successfully predicted.
  • Evidence snippets:
  • Snippet 1 (score: 0.465) > Following SARS-CoV-2 infection, some COVID-19 patients experience severe host driven adverse events. To treat these complications, their underlying etiology and drug treatments must be identified. Thus, a novel AI methodology MOATAI-VIR, which predicts disease-protein-pathway relationships and repurposed FDA-approved drugs to treat COVID-19’s clinical manifestations was developed. SARS-CoV-2 interacting human proteins and GWAS identified respiratory failure genes provide the input from which the mode-of-action (MOA) proteins/pathways of the resulting disease comorbidities are predicted. These comorbidities are then mapped to their clinical manifestations. To assess each manifestation’s molecular basis, their prioritized shared proteins were subject to global pathway analysis. Next, the molecular features associated with hallmark COVID-19 phenotypes, e.g. unusual neurological symptoms, cytokine storms, and blood clots were explored. In practice, 24/26 of the major clinical manifestations are successfully predicted. Three major uncharacterized manifestation categories including neoplasms are also found. The prevalence of neoplasms suggests that SARS-CoV-2 might be an oncovirus due to shared molecular mechanisms between oncogenesis and viral replication. Then, repurposed FDA-approved drugs that might treat COVID-19’s clinical manifestations are predicted by virtual ligand screening of the most frequent comorbid protein targets. These drugs might help treat both COVID-19’s severe adverse events and lesser ones such as loss of taste/smell.

[6] Immune and Metabolic Signatures of COVID-19 Revealed by Transcriptomics Data Reuse

  • Authors: L. Gardinassi, C. O. Souza, Helioswilton Sales-Campos, S. Fonseca
  • Year: 2020
  • Venue: Frontiers in Immunology
  • URL: https://www.semanticscholar.org/paper/88b6bf5f42d644dbb591a33e5733b65220ff4b88
  • DOI: 10.3389/fimmu.2020.01636
  • PMID: 32670298
  • PMCID: 7332781
  • Citations: 108
  • Influential citations: 5
  • Summary: Results indicate higher expression of genes related to oxidative phosphorylation both in peripheral mononuclear leukocytes and BALF, suggesting a critical role for mitochondrial activity during SARS-CoV-2 infection.
  • Evidence snippets:
  • Snippet 1 (score: 0.457) > The current pandemic of coronavirus disease 19 (COVID-19) has affected millions of individuals and caused thousands of deaths worldwide. The pathophysiology of the disease is complex and mostly unknown. Therefore, identifying the molecular mechanisms that promote progression of the disease is critical to overcome this pandemic. To address such issues, recent studies have reported transcriptomic profiles of cells, tissues and fluids from COVID-19 patients that mainly demonstrated activation of humoral immunity, dysregulated type I and III interferon expression, intense innate immune responses and inflammatory signaling. Here, we provide novel perspectives on the pathophysiology of COVID-19 using robust functional approaches to analyze public transcriptome datasets. In addition, we compared the transcriptional signature of COVID-19 patients with individuals infected with SARS-CoV-1 and Influenza A (IAV) viruses. We identified a core transcriptional signature induced by the respiratory viruses in peripheral leukocytes, whereas the absence of significant type I interferon/antiviral responses characterized SARS-CoV-2 infection. We also identified the higher expression of genes involved in metabolic pathways including heme biosynthesis, oxidative phosphorylation and tryptophan metabolism. A BTM-driven meta-analysis of bronchoalveolar lavage fluid (BALF) from COVID-19 patients showed significant enrichment for neutrophils and chemokines, which were also significant in data from lung tissue of one deceased COVID-19 patient. Importantly, our results indicate higher expression of genes related to oxidative phosphorylation both in peripheral mononuclear leukocytes and BALF, suggesting a critical role for mitochondrial activity during SARS-CoV-2 infection. Collectively, these data point for immunopathological features and targets that can be therapeutically exploited to control COVID-19.

[7] Potential association between COVID-19 and neurological disorders: analysis of common genes and therapeutics

  • Authors: Wenzhi Chen, Shishi Jiang, Cheng Li, Shu Li, Junling Wang et al.
  • Year: 2024
  • Venue: Frontiers in Neurology
  • URL: https://www.semanticscholar.org/paper/5fdfdc4586aed3809ce5c6c4fcc7130b408ab7c8
  • DOI: 10.3389/fneur.2024.1417183
  • PMID: 39469068
  • PMCID: 11513677
  • Citations: 1
  • Summary: A comprehensive study aimed at exploring the relationship between COVID-19 and various neurological disorders, with a particular focus on the shared dysregulated genes and the potential therapeutic targets, exploring the common molecular mechanisms and the potential treatment pathways.
  • Evidence snippets:
  • Snippet 1 (score: 0.457) > Our research aims to explore this potential molecular overlap through the bioinformatics analysis. > The selection of diseases for our study is not arbitrary but is based on the known clinical associations between COVID-19 and various neurological diseases, such as AD and PD. These diseases share some common features such as neuroinflammation and the oxidative stress, which provide a reasonable basis for our investigation. By comparing the transcriptomic data of these diseases with COVID-19, we aim to uncover their common molecular mechanisms and the potential therapeutic pathways. > In this study, we selected six common COVID-19-related neurological diseases, including the hemorrhagic stroke (HS), the ischemic stroke (IS), PD, AD, epilepsy (EP) and sleep disorders (SD), for the bioinformatics analysis of their interaction with COVID-19. From the perspective of the gene interactions, we aim to elucidate the reasons for the occurrence of the neurological complications during the acute phase of the SARS-CoV-2 infection and the potential pathogenic mechanisms of the long COVID neurological symptoms. > The six neurological diseases we selected (including AD, epilepsy, stroke, PD, and the sleep disorders) may share some commonalities in pathogenesis and pathophysiology, such as the inflammatory responses and apoptosis. Therefore, by analyzing the common dysregulated genes of these diseases and combining the protein-protein interaction network analysis, the gene regulatory network analysis, and the protein-drug interaction network analysis, we can reveal the potential shared biological mechanisms between COVID-19 and the neurological diseases, thereby providing the new insights and strategies for the treatment of the related diseases.

[8] After the virus has cleared—Can preclinical models be employed for Long COVID research?

  • Authors: Ethan B Jansen, S. N. Orvold, C. Swan, Anthony Yourkowski, Brittany Thivierge et al.
  • Year: 2022
  • Venue: PLoS Pathogens
  • URL: https://www.semanticscholar.org/paper/c2ce8b85ae1ff3875e2c82ab99c68f0d80873a68
  • DOI: 10.1371/journal.ppat.1010741
  • PMID: 36070309
  • PMCID: 9451097
  • Citations: 19
  • Influential citations: 1
  • Summary: The establishment of a recognized Long COVID preclinical model representing the human condition would allow the identification of mechanisms causing disease as well as serve as a vehicle for evaluating potential therapeutics.
  • Evidence snippets:
  • Snippet 1 (score: 0.455) > There are a growing number of therapeutics in clinical trials for Long COVID, with over 400 registered on NIH.gov [175]. Most trials focus on treatments for pulmonary manifestations, with others in development for extra-respiratory complications such as neurological or CVCs [175]. However, our lack of understanding regarding the multiorgan pathogenic mechanisms of PASC makes the development of effective therapeutics challenging. Therefore, relevant PASC animal models will be crucial in developing novel therapeutics or repurposing available therapeutics to address the wide range of long-term symptoms. Some examples of therapeutics currently being tested in Long COVID patients include repurposed therapeutics for autoimmune diseases, anti-inflammatory treatments, and even dietary supplements. > A Phase II study of the ribonuclease RSLV-132 is underway in Long COVID patients (NCT04944121). RSLV-132 is an RNase-Fc fusion protein designed to treat autoimmune diseases such as lupus and Sjo ¨gren's syndrome [176,177]. The drug digests extracellular RNA to prevent activation of the immune system via toll-like receptors and the interferon pathway [176]. A study in macaques detected sub-genomic viral RNA persisting in the lungs; therefore, this may be an interesting model to test RSLV-132's efficacy and ability to prevent post-acute pathology [154]. Ferrets may also be used as viral RNA was detected throughout the body [149]. Sodium pyruvate nasal spray is another therapeutic currently in clinical trials for the treatment of Long COVID (NCT04871815). Sodium pyruvate impairs inflammatory cytokine production (IL-6, IL-1β, and TNF-α) in macrophages during Influenza A virus infection [178] and has been tested in clinical trials for acute COVID-19 and now Long COVID [179]. Results from a study of 22 Long COVID patients suggested improvements in headaches, coughing or sneezing, and breathing difficulties [179]. Unfortunately, this study was not randomized and contained no placebo controls.

[9] Multi-omics approach to COVID-19: a domain-based literature review

  • Authors: C. Montaldo, F. Messina, I. Abbate, M. Antonioli, V. Bordoni et al.
  • Year: 2021
  • Venue: Journal of Translational Medicine
  • URL: https://www.semanticscholar.org/paper/0c7804617654881ff5b118da3e412f1a4b3339c4
  • DOI: 10.1186/s12967-021-03168-8
  • PMID: 34876157
  • PMCID: 8649311
  • Citations: 17
  • Influential citations: 1
  • Summary: The analysis revealed that dysregulated pathways of innate immune responses can affect COVID-19 progression and outcomes, and multi-omics approach may help to further investigate unknown aspects of the disease.
  • Evidence snippets:
  • Snippet 1 (score: 0.452) > Omics data, driven by rapid advances in laboratory techniques, have been generated very quickly during the COVID-19 pandemic. Our aim is to use omics data to highlight the involvement of specific pathways, as well as that of cell types and organs, in the pathophysiology of COVID-19, and to highlight their links with clinical phenotypes of SARS-CoV-2 infection. The analysis was based on the domain model, where for domain it is intended a conceptual repository, useful to summarize multiple biological pathways involved at different levels. The relevant domains considered in the analysis were: virus, pathways and phenotypes. An interdisciplinary expert working group was defined for each domain, to carry out an independent literature scoping review. The analysis revealed that dysregulated pathways of innate immune responses, (i.e., complement activation, inflammatory responses, neutrophil activation and degranulation, platelet degranulation) can affect COVID-19 progression and outcomes. These results are consistent with several clinical studies. Multi-omics approach may help to further investigate unknown aspects of the disease. However, the disease mechanisms are too complex to be explained by a single molecular signature and it is necessary to consider an integrated approach to identify hallmarks of severity.

[10] Severe Acute Respiratory Syndrome Coronavirus 2: From Gene Structure to Pathogenic Mechanisms and Potential Therapy

  • Authors: Jun Wu, Xiaohui Yuan, Bing Wang, Rui Gu, Wei Li et al.
  • Year: 2020
  • Venue: Frontiers in Microbiology
  • URL: https://www.semanticscholar.org/paper/699c43b38b76cbd7ff08dc13dd2d8ca2eb1577ee
  • DOI: 10.3389/fmicb.2020.01576
  • PMID: 32719672
  • PMCID: 7347906
  • Citations: 36
  • Influential citations: 2
  • Summary: The correlations among gene structure, protein function, and pathogenic mechanisms of SARS-CoV-2 are refined and potential therapeutic targets are discussed, aiming to accelerate the advanced design and development of vaccines and therapeutic drugs against COVID-19.
  • Evidence snippets:
  • Snippet 1 (score: 0.451) > be developed to prevent and treat COVID-19 and reduce the serious impact on human beings. For this purpose, detailed information about the pathogenesis of COVID-19 at the cellular and molecular levels is urgently needed. In this review, we summarized the current understanding of gene structure, protein function and pathogenic mechanisms of SARS-CoV-2, Based on the above, we refined the correlations among gene structure, protein function, and pathogenic mechanisms of SARS-CoV-2. Importantly, we further discussed potential therapeutic targets, aiming to accelerate the advanced design and development of vaccines and therapeutic drugs against COVID-19.

[11] Landscape of Molecular Crosstalk Perturbation between Lung Cancer and COVID-19

  • Authors: Aditi Kuchi, Jiande Wu, J. Fuloria, C. Hicks
  • Year: 2022
  • Venue: International Journal of Environmental Research and Public Health
  • URL: https://www.semanticscholar.org/paper/9094685853a78a21c392c5aed65c33e8896a6671
  • DOI: 10.3390/ijerph19063454
  • PMID: 35329141
  • PMCID: 8953719
  • Citations: 5
  • Summary: A signature of genes associated with both diseases and signatures of genes uniquely associated with each disease are revealed, confirming crosstalk in molecular perturbation between COVID-19 and lung cancer.
  • Evidence snippets:
  • Snippet 1 (score: 0.448) > Some of the major challenges in clinical management of COVID-19 include extrapulmonary manifestations of the disease and its effects on multiple organs, including the lungs [40][41][42]. Extrapulmonary manifestations include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary disease syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms and dermatologic complications [40][41][42][43]. Although we did not investigate the association of the discovered genes with extrapulmonary manifestations in COVID-19, the discovery of genes with multiple overlapping functions involved in many biological processes suggests that some of the identified genes and gene regulatory networks may be involved in extrapulmonary activities. Moreover, the lung as an organ is likely to function in unison with other organs. Under such conditions, the effects of COVID-19 on the lungs have potential to trigger a cascade of events likely to affect other organs and lead to extrapulmonary manifestations. Indeed, lungs as organs contain many cells that can play many different roles. Although we did not examine individual lung cells, previous studies have shown that transcription profiling could reveal novel mechanisms of SARS-CoV-2 infection in human lung cells [44,45]. > Another finding of significance in this investigation was the discovery of gene regulatory networks and signaling pathways associated with both diseases. This suggests that the host-pathogen interactions linking the two diseases are complex. The novel as-pect and clinical significance of this finding is that it could increase our understanding of host-pathogen interactions, a critical step in vaccine and drug development [46]. For example, the discovery of the coronavirus pathogenesis signaling pathway in this study has the promise to increase our understanding of the pathogenesis of COVID-19 and the molecular mechanisms driving the disease. Although signatures of genes associated with COVID-19 have been reported [17,21], molecular crosstalk perturbation between COVID-19 and lung cancer has not been reported.

[12] Exploring Potential Biomarkers and Molecular Mechanisms of Ischemic Cardiomyopathy and COVID-19 Comorbidity Based on Bioinformatics and Systems Biology

  • Authors: Simin Luo, Xuan Zhang, Xiang Xiao, W. Luo, Zixuan Yang et al.
  • Year: 2023
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/c8332001924d48129287cd1324bf6ab86da82343
  • DOI: 10.3390/ijms24076511
  • PMID: 37047484
  • PMCID: 10094917
  • Citations: 5
  • Summary: It is shown that co-pathogenesis of ICM and COVID-19 may be related to angiogenesis, and that vindesine and ON-01910 were predicted as potential therapeutic agents.
  • Evidence snippets:
  • Snippet 1 (score: 0.443) > The workflow of this study is shown in Figure 1. We analyzed two high-throughput sequencing datasets (GSE164805 and GSE5406) that we downloaded from the Gene Expression Omnibus (GEO). We used an integrated bioinformatics and systems biology approach to identify differentially expressed genes (DEGs) and explored their molecular mechanisms in COVID-19 and ICM. These genes provide an entry point to explore the common clinical phenotypes of COVID-19 and ICM. The protein-protein interaction (PPI) analysis identified key hub genes. To explore the diagnostic performance for these hub genes, we downloaded two other GEO datasets (GSE116250 and GSE211979) and plotted receiver operating characteristic (ROC) curves. Transcription factor (TF) and microRNA (miRNA) regulatory networks for these genes were constructed. We identified potential therapeutic agents by drug prediction, and validated them by molecular docking computer simulations. > Ischemic cardiomyopathy (ICM) reduces or stops blood flow to the heart, leading to myocardial damage [13]. In a systematic review, Omidi et al. [14] found that cardiomyopathy was a very common cardiovascular complication of COVID-19. The autopsy pathology of patients with COVID-19 found microscopic evidence that suggested acute ischemic injury [15]. Impaired cardiac systolic function was detected in patients with COVID-19 and ICM by cardiac computed tomography [16]. However, the common pathogenesis of ICM and COVID-19 remains to be fully elucidated. > Disease-disease relationships play important roles in the pathobiological manifestations of diseases and in their precise treatment [17]. Exploring disease associations can enhance the understanding of connections between diseases, which can help in developing diagnostic, prognostic, and treatment strategies [18]. Mutations in functionally relevant genes are known to be responsible for overlapping clinical phenotypes of different diseases. Therefore, in this study, we focused on key genes in ICM that are connected to the pathogenesis of COVID-19. The workflow of this study is shown in Figure 1.

[13] Epidemiology, Symptoms and Pathophysiology of Long Covid Complications

[14] Cutaneous Manifestations in Patients With COVID-19: Clinical Characteristics and Possible Pathophysiologic Mechanisms

  • Authors: F. González, C. Correa, E. Contreras, R. Agudo, Severo
  • Year: 2020
  • Venue: Actas Dermo-Sifiliograficas
  • URL: https://www.semanticscholar.org/paper/979d18b1f483a260b011a536cc10bb7dfae9629f
  • DOI: 10.1016/j.adengl.2021.01.024
  • PMID: 34012165
  • PMCID: 7843072
  • Citations: 31
  • Influential citations: 1
  • Summary: Graphical Abstract
  • Evidence snippets:
  • Snippet 1 (score: 0.439) > The COVID-19 pandemic has created enormous challenges for health care professionals, including the need to keep abreast with the vast spectrum of clinical manifestations associated with this disease. COVID-19 is a multisystemic disease that affects multiple organs, including the skin. The occurrence of cutaneous manifestations, however, represents an advantage, as their recognition can lead to early suspicion of disease in some cases and provide clues about individual immune responses or complications in others. > Based on the pathophysiological mechanisms hypothesized, we propose classifying the various cutaneous manifestations of COVID-19 into 2 groups: 1) manifestations primarily linked to a direct cytopathogenic effect on cells such as keratinocytes, which are involved in many known viral infections (morbilliform or urticarial rashes, reactions similar to drug eruptions, varicella-like lesions) and 2) manifestations linked to an uncontrolled release of cytokines due to alterations in specific white blood cells, such as T cells and macrophages. This second group could be divided into a further 2 groups: 1) manifestations characterized by features similar to those seen in macrophage activation syndrome (acral ischemia, gangrene, retiform purple, livedo racemosa) and associated with poor outcomes in terms of morbidity and mortality and 2) cutaneous manifestations with a mild, self-limiting disease course, observed in young patients and linked to the activation of an early type I IFN response (chilblain-like lesions) (Fig. 7). This hypothesis is one of the first in the literature to provide a possible explanation of the pathophysiological mechanisms underlying the main cutaneous manifestations of COVID-19; it also provides a means of classifying these manifestations and establishing their possible prognostic value. > We believe that it is paramount for physicians, nurses, respiratory therapists, health care professionals still in training, and even members of the general population to be aware of the relationship between SARS-CoV-2 infection and the skin and its various manifestations. Heightened awareness will promote an active search for manifestations and a detailed study of cases, adding to the scientific knowledge and our understanding of the pathophysiology of COVID-

[15] Mechanistic modeling of the SARS-CoV-2 disease map

  • Authors: Kinza Rian, M. Esteban-Medina, Marta R. Hidalgo, C. Çubuk, M. M. Falco et al.
  • Year: 2020
  • Venue: BioData Mining
  • URL: https://www.semanticscholar.org/paper/aaf4d9b3ef75711609791b736ba048ab52657727
  • DOI: 10.1186/s13040-021-00234-1
  • PMID: 33478554
  • PMCID: 7817765
  • Citations: 18
  • Summary: A web interface that implements a comprehensive mechanistic model of the SARS-CoV-2 disease map that provides an unprecedentedly detailed view of the mechanisms of viral invasion and the consequences in the cell has the potential of becoming an invaluable asset in the search for efficient antiviral treatments.
  • Evidence snippets:
  • Snippet 1 (score: 0.438) > The recent pandemic of COVID-19 (Coronavirus Disease-2019), an emerging respiratory disease caused by the SARS-CoV-2 virus, which spread more efficiently than previous highly pathogenic coronaviruses SARS-CoV and MERS-CoV, has led to a tremendous toll of affected cases and over 500,000 fatalities in more than 200 countries since its first outbreak in late 2019 [1]. Precisely due to the rapid transmission of this novel pathogen, no antiviral drugs or vaccines are available for SARS-CoV-2. > Understanding the molecular mechanisms that mediate SARS-CoV-2 infection is key for the rapid development of efficient preventive or therapeutic interventions against the COVID-19. A comprehensive description of such molecular mechanisms is represented in the corresponding disease map, that is, the sub-module of the whole pathway of known human protein functional interactions that summarize details of the disease mechanism and consequently are relevant for understanding the disease [2]. The recent availability of a detailed catalog of viral-human protein interactions [3] has facilitated the construction of a first version of a map of the human molecular pathways involved in the viral infection and downstream consequences [4]. > Disease maps are repositories of knowledge of disease-relevant mechanisms that provide qualitative guidance for the interpretation of experimental findings [2]. Actually, disease maps are the supporting foundation of different tools able to model the information contained in them in order to provide a detailed quantitative explanation for experimental results [5]. In particular, mechanistic models of disease maps are becoming increasingly relevant for genomic data interpretation because they provide a natural link between omics data measurements and cell behavior and outcome [6], which ultimately accounts for the phenotype of the infection. The knowledge of these links allows a better understanding of the molecular mechanisms of the viral infection and the responses to drugs. Actually, mechanistic models of human signaling [7] or metabolic pathways [8] have been successfully used to uncover specific molecular mechanisms behind different cancers [7,[9][10][11], rare [12] and common [13] diseases, to reveal mechanisms of action of drugs [14], and dissecting them at single cell level [15], to suggest personalized treatments [16,17] and in

[16] Immune responses in mildly versus critically ill COVID-19 patients

  • Authors: H. Nasrollahi, A. Talepoor, Zahra Saleh, Mahsa Eshkevar Vakili, Paria Heydarinezhad et al.
  • Year: 2023
  • Venue: Frontiers in Immunology
  • URL: https://www.semanticscholar.org/paper/6926dff6701efe3a438e6835511b1d9e2abaf620
  • DOI: 10.3389/fimmu.2023.1077236
  • PMID: 36793739
  • PMCID: 9923185
  • Citations: 43
  • Influential citations: 1
  • Summary: The role of immunity in the development and progression of COVID-19 is discussed, focusing on molecular and cellular aspects of the immune system in mild vs. severe forms of the disease.
  • Evidence snippets:
  • Snippet 1 (score: 0.434) > At this point in the pandemic, further understanding of the SARS-CoV-2 biology and systemic host immune responses can provide information on the processes and mechanisms involved in immunemediated viral clearance and define specific targets for the treatment of COVID-19. Recent research on the immune mechanisms in COVID-19 refer to the initiation of infection by SARS-CoV-2 accompanied by cellular immune responses, including specifically poly-functional CD4 + and CD8 + T cell responses, which may become chronic along with immune inflammation. Recovery from tissue injury, prolonged inflammation and deviations in adaptive immune activity may play a role in the postinfectious complications, termed post-COVID. The consequences of deviated immune processes also depend on genetic make-up and environmental risk factors. Due to the SARS-CoV-2 contagiousness, the increased risk of death and the need for an ICU in severe cases of the disease, there is an urgent need for long-term follow-up of the molecular and cellular mechanisms in virus-host communication at all stages of the disease. This information is needed for delineating the optimal management of infected patients in order to prevent the progression to severe forms of the disease. Currently, ongoing large clinical trials based on antiviral and immune-based treatments may soon provide efficient therapeutic agents for COVID-19 patients. In any case, vaccination still remains the best means for preventing severe illness.

[17] Evidence mapping and review of long-COVID and its underlying pathophysiological mechanism

  • Authors: A. Umesh, K. Pranay, R. C. Pandey, M. Gupta
  • Year: 2022
  • Venue: Infection
  • URL: https://www.semanticscholar.org/paper/e37c25911ace618b3a5a42a186dbcf630ee53c01
  • DOI: 10.1007/s15010-022-01835-6
  • PMID: 35489015
  • PMCID: 9055372
  • Citations: 34
  • Summary: The review highlights that pulmonary, neuro-psychological, and cardiovascular complications are major findings in most epidemiological studies, however, dysfunctional gastrointestinal, endocrine, and metabolic health are recent findings for which underlying pathophysiological mechanisms are poorly understood.
  • Evidence snippets:
  • Snippet 1 (score: 0.431) > Evidence mapping and review of long-COVID and its underlying pathophysiological mechanism

[18] Neuroprotective potentials of ferulic acid against intracerebral hemorrhage COVID-19 through using network pharmacology approach and molecular docking analysis

  • Authors: Qinghua Dong, Yongxing Tan, Gangjian Tang, Zhonghui Wu, Aiguo Li et al.
  • Year: 2023
  • Venue: Current Research in Toxicology
  • URL: https://www.semanticscholar.org/paper/657cbcc0a0084608b1196cf4df5ce702f1a4bb8c
  • DOI: 10.1016/j.crtox.2023.100123
  • PMID: 37731942
  • PMCID: 10507130
  • Citations: 8
  • Summary: Graphical abstract
  • Evidence snippets:
  • Snippet 1 (score: 0.429) > In the current study, results from network pharmacology analysis ascertained total eleven intersection targets among ferulic acid, COVID-19 and ICH. To further integrate functional relevancy within intersection genes, the PPI network characterized protein-protein interactions before further identified all core targets based on degree value assessment, and the core targets included EGFR, ICAM1, ACE, F3, TLR4, NOS3. These core genes might act as the pharmacological targets in ferulic acid against COVID-19 and ICH before functional verification of the biological features in these core genes. Further drug combination using ferulic acid and medicine targeted core proteins may be optimized for clinical treatment of COVID-19 and ICH. Additionally, GO and KEGG functional assays were conducted to reveal the molecular mechanisms of ferulic acid against COVID-19 and ICH. We integrated signaling pathways from core targets-based annotations. Among current pathways including Coronavirus disease-COVID-19, and Influenza A were chiefly implicated in viral infectious disorders, implying that ferulic acid might possess a potential antiviral mechanism against COVID-19. Other molecular pathways, including phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway and NF-kappa B signaling pathway should be characterized accordingly in current enrichment analysis. It is reported that the nuclear factor kappaB (NF-κB) pathway relates to release of proinflammatory cytokines induced by infection (Yu et al, 2022). The PI3K/ AKT signaling pathway is found with positive involvement in inflammation development (He et al, 2022). Collectively, it is surmised that cytokine storm is one of the leading causes of COVID-19 patients with ICH. Thus, anti-viral and anti-inflammatory functions may be involved in the preliminary beneficial mechanism in ferulic acid in the treatment of COVID-19 and ICH. As highlighted in enriched signaling pathways, we speculated that anti-COVID-19 and ICH mechanisms of ferulic acid might exerted via regulating multiple KEGG molecular pathways. > Among identified core targets, molecular docking analysis was applied to determine the binding capability of core targets with ferulic acid.

[19] Integrated bioinformatics analysis identifies RPS27A and PPP2R1A as shared hub genes in heart failure and COVID-19

  • Authors: Tong Lang, Xinyu Liu, Ling-bing Meng
  • Year: 2025
  • Venue: Journal of Cardiothoracic Surgery
  • URL: https://www.semanticscholar.org/paper/a6427a61cb6197d1d9037ecb7a7318f476fe4937
  • DOI: 10.1186/s13019-025-03634-0
  • PMID: 41153026
  • PMCID: 12570859
  • Citations: 1
  • Summary: Five core genes, including RPS27A and PPP2R1A, both of which were significantly upregulated in HF and COVID-19 samples, offer potential cross-disease biomarkers and therapeutic targets for conditions driven by inflammation and immune dysregulation.
  • Evidence snippets:
  • Snippet 1 (score: 0.428) > Heart failure (HF) remains a major global health challenge, characterized by impaired cardiac output and often accompanied by comorbidities such as hypertension, coronary artery disease, and diabetes. Despite therapeutic advances, HF continues to be a leading cause of morbidity and mortality, especially in older populations [1][2][3]. > Coronavirus disease 2019 (COVID- 19), caused by the SARS-CoV-2 virus, emerged in 2019 and rapidly evolved into a global pandemic [4]. While primarily affecting the respiratory system, COVID-19 also has profound systemic effects, including cardiovascular complications such as myocardial injury, arrhythmias, and worsening of pre-existing HF [5,6]. Severe cases are frequently associated with cytokine storms, coagulation dysfunction, and widespread pulmonary inflammation. > Although HF and COVID-19 differ in clinical presentation and etiology, recent evidence suggests that they may share underlying molecular mechanisms. Inflammation, immune dysregulation, and cellular stress responses are common hallmarks of both conditions. Additionally, both diseases have been associated with chromosomal instability, genetic alterations, and aberrant gene expression patterns, highlighting the importance of identifying convergent molecular pathways. > The advent of next-generation sequencing (NGS) technologies and the availability of large-scale public transcriptomic datasets have enabled the use of bioinformatics tools to systematically explore disease-related genes and signaling pathways [7]. Such integrative analyses can reveal novel biomarkers and therapeutic targets, offering insights into complex disease mechanisms [8]. > Among the genes of interest, RPS27A encodes a ribosomal protein essential for ribosome biogenesis and protein translation [9]. It is synthesized as a ubiquitin-fused protein and plays additional roles in cell growth, proliferation, and apoptosis. PPP2R1A encodes a scaffolding subunit of protein phosphatase 2 A (PP2A), a serine/ threonine phosphatase involved in regulating pathways linked to inflammation, cell cycle, and stress response [10]. While both genes have been implicated in various pathological processes, their specific involvement in HF and COVID-19 remains unclear.

[20] Exploring the interplay between host genetics and acute and long COVID: A narrative review

  • Authors: Thais Beuren, Filipe Ferrari, Leandro Franzoni, C. Goulart, F. Val et al.
  • Year: 2025
  • Venue: Clinics
  • URL: https://www.semanticscholar.org/paper/3d705603df0ab13c959bed2cc51c686cd8989977
  • DOI: 10.1016/j.clinsp.2025.100708
  • PMID: 40543387
  • PMCID: 12216730
  • Citations: 1
  • Summary: Some polymorphisms worsen outcomes; others may offer protection in COVID-19 patients and gene effects likely interact with environmental and biological factors.
  • Evidence snippets:
  • Snippet 1 (score: 0.426) > The interplay between genetic factors and COVID-19 has revealed a complex landscape of both risk and protection. The main genes and polymorphisms associated with the clinical presentations of acute COVID-19 and long COVID discussed in this review are summarized in Table 1. > Over the past few years, research has illuminated how various genetic variants can influence susceptibility to infection, severity of disease, and even long-term outcomes. For instance, some polymorphisms affect immune responses, while others impact viral entry efficiency or modulate inflammatory pathways. Understanding these genetic mechanisms at the molecular level is essential for exploring their potential clinical and biological implications. Nonetheless, such findings should be interpreted with caution, as many reported associations may be correlative rather than causative and are often influenced by a range of non-genetic factors. > This expanding body of evidence not only aids in identifying individuals at increased risk but also paves the way for personalized medicine strategies in the management and treatment of COVID-19. For example, if specific genetic variants are shown to influence immune regulation, therapies targeting these pathwayssuch as cytokine modulatorscould be considered for patients with high-risk genotypes. Likewise, insights into gene mutations involved in viral entry or replication may inform antiviral strategies, including drug repurposing or the development of new therapeutic agents tailored to individual genetic profiles. > The investigation of genetic determinants related to COVID-19 severity and protection remains a dynamic and evolving field. Substantial progress has been made in identifying how genetic variation can influence outcomes, but it is essential to recognize that genetics is only one component of a multifactorial framework. Age, comorbidities, ethnicity, and environmental factors also play critical roles. The interaction between genetic and non-genetic factors adds complexity to the understanding of risk assessment. > By elucidating the genetic mechanisms underlying COVID-19 susceptibility and progression, researchers aim to develop more accurate tools for risk stratification and more precise therapeutic interventions (Fig. 1). This could ultimately lead to more proactive and effective disease management strategies that benefit patients on a global scale. > Continued research in this field holds great promise for advancing personalized medicine, guiding preventive measures, and enabling the development of novel therapeutics tailored to individual genetic backgrounds.

Notes

  • This provider combines search_papers_by_relevance with snippet_search.
  • No synthesis or second-stage model call is performed.