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Bioinformatics analysis of the 45 proteins changed in expression in the same direction in blood samples from patients with severe COVID-19 vs less severe or healthy individuals. Gene ontology analysis of the differentially expressed proteins from Table S2 using DAVID identified enriched terms associated with (A) biological process and (B) molecular function. Only terms with three or more proteins mapped to them are shown. DEPs: differentially expressed proteins.
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With the rising demand for improved COVID-19 disease monitoring and prognostic markers, studies have aimed to identify biomarkers using a range of screening methods. However, the selection of biomarkers for validation from large datasets may result in potentially important biomarkers being overlooked when datasets are considered in isolation. Here,...
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... ontology analysis using DAVID software identified a range of biological and molecular process terms that were enriched among the proteins with a consistent direction of change across the COVID-19 biomarker studies from Table S2 (Fig. 1). Perhaps unsurprisingly, the top biological process term was "inflammatory response" with six proteins increased in expression in severe COVID-19 vs less severe or healthy mapping to it (i.e., C-reactive protein (CRP), S100 calciumbinding protein A8 and A9 (S100A8; S100A9), orosomucoid 1(ORM1), pro-platelet basic protein (PPBP), and ...
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... S100A9), orosomucoid 1(ORM1), pro-platelet basic protein (PPBP), and alpha 1-antichymotrypsin Table 1 Overview of COVID-19 biomarker studies. The publications included within this study that aimed to identify biomarkers of COVID-19. DEPs -differentially expressed proteins; ICU -intensive care unit; WHO -World Health Organisation. [27] (SERPINA3)) (Fig. 1A). Other enriched biological process terms among the increased proteins included "acute phase response" (n = 5 proteins), "neutrophil chemotaxis" (n = 4 proteins) and "platelet degranulation" (n = 4 proteins). Enriched molecular process terms among these proteins included "protein binding" (n = 6), calcium ion binding (n = 5) and RAGE ...
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... biological process terms among the increased proteins included "acute phase response" (n = 5 proteins), "neutrophil chemotaxis" (n = 4 proteins) and "platelet degranulation" (n = 4 proteins). Enriched molecular process terms among these proteins included "protein binding" (n = 6), calcium ion binding (n = 5) and RAGE receptor binding (n = 3) (Fig. 1B). Proteins decreased in expression in severe COVID-19 vs less severe or healthy mostly mapped to terms relating to metabolic processes and cholesterol / lipid transport and remodeling, with the top hit being "lipoprotein metabolic process" (n = 4 proteins) (Fig. 1A), "phosphatidylcholine binding" (n = 3 proteins) and "lipase inhibitor ...
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... binding" (n = 6), calcium ion binding (n = 5) and RAGE receptor binding (n = 3) (Fig. 1B). Proteins decreased in expression in severe COVID-19 vs less severe or healthy mostly mapped to terms relating to metabolic processes and cholesterol / lipid transport and remodeling, with the top hit being "lipoprotein metabolic process" (n = 4 proteins) (Fig. 1A), "phosphatidylcholine binding" (n = 3 proteins) and "lipase inhibitor activity" (n = 3 proteins) (Fig. ...
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... in expression in severe COVID-19 vs less severe or healthy mostly mapped to terms relating to metabolic processes and cholesterol / lipid transport and remodeling, with the top hit being "lipoprotein metabolic process" (n = 4 proteins) (Fig. 1A), "phosphatidylcholine binding" (n = 3 proteins) and "lipase inhibitor activity" (n = 3 proteins) (Fig. ...
Citations
... The outcomes of the aforementioned enrichment analysis indicate the potential signi cance of immune and in ammatory responses in the context of both OA and COVID-19. Research has demonstrated that severe COVID-19 cases manifest severe lymphopenia, robust T-cell activation, and heightened expression of T-cell suppressor molecules31 . Disruption in the regulation of leukocyte activation ultimately triggers irregular immune cell activation, cytokine storms, and systemic in ammatory responses. ...
Background
The emergence of severe coronavirus disease 2019 (COVID-19) and its ensuing complications presents a substantial challenge to human safety. Osteoarthritis (OA) stands as the most common degenerative joint disease, while the intricate molecular relationship between OA and COVID-19 remains enigmatic. In this investigation, we employed systematic bioinformatics analysis to uncover the underlying molecular mechanisms associated with these two diseases. Additionally, we identified potential therapeutic drugs with the potential to aid in the treatment of patients afflicted with both COVID-19 infection and osteoarthritis (OA).
Methods
Datasets for both COVID-19 and OA were sourced from the GEO database. Subsequently, a differential expression analysis was executed to procure Differentially Expressed Genes (DEGs). Co-expressed genes shared between OA and COVID-19 were identified through the intersection of differential gene sets, employing a Venn diagram. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Metascape. The hub genes were identified through protein-protein interaction (PPI) analysis carried out in Cytoscape, and their validity was subsequently affirmed through brief experiment. Finally, transcription factor-gene interactions, microRNA (miRNA) candidate identification and drug candidate identification were identified by co-expression of genes.
Results
A total of 94 co-expressed DEGs were obtained. GO and KEGG enrichment analysis of DEGs showed that they mainly affect inflammation, cytokine and immune-related functions, and inflammation-related signaling pathways. Through the analysis of the PPI network, we obtained 9 hub genes, and validated them with brief experiments. In addition, the top ten drug candidates ranked by P-value were screened, which may exhibit potential for providing therapeutic benefits in the context of treating individuals affected by both COVID-19 infection and OA.
Conclusion
This study reveals a shared molecular mechanism between osteoarthritis (OA) and neocoronary pneumonia. Additionally, it clarifies potential mechanisms linked to synovial lesions in both neocoronary pneumonia and osteoarthritis. These shared pathways and hub genes might offer insights for future investigations.
... Among the cytokines, the earliest report on Tocilizumab, an anti-IL-6 receptor for treatment of a patient with COVID-19 related lung disease [26] opened possibilities for severe cases. Recent meta-analysis also revealed that IL-6 is a master regulator of COVID-19 severity biomarkers [27]. In addition, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein S1 subunit activates TLR4 signaling to induce pro-inflammatory responses in murine and human macrophages. ...
COVID-19 patients suffer from detrimental effects of cytokine storm and not much success has been achieved to overcome this issue. We sought to test the ability of selenium in reducing the impact of two important cytokine storm players; IL-6 and TNF-a. The effects of four selenium compounds were evaluated on the secretion of these cytokines from THP-1 macrophages in vitro following LPS challenge. Also, potential impact of methylseleninic acid (MSeA) on Nrf2 and IkBa was determined following short treatment of THP-1 macrophages. MSeA was observed to be the most potent selenium form to reduce IL-6 and TNF-a levels among the four selenium compounds tested. In addition, an increase in Nrf2 and decrease in pIkBa in human macrophages was observed following MSeA treatment. Our data indicate that COVID-19 patients might benefit by suppressing their cytokine storm with addition of MSeA to the standard therapy.
... Interestingly, complex physiological interactions and individual variations are apparent in oxygen levels and hormonal, inflammatory and immune responses in the body. Controversial results in previous studies might thus have been due to wide individual variations in such responses to HH. Cytokine storm in coronavirus disease 2019 (COVID-19) has been speculated to involve the secretion of various cytokines, particularly IL-6 as a key mediator 53 . However, in COVID-19, the meta-analysis showed IL-6 levels of 36.7 pg/mL (95% confidence interval [CI] 21.6-62.3 ...
When lowlanders are exposed to environments inducing hypobaric hypoxia (HH) such as high mountains, hemodynamic changes occur to maintain oxygen levels in the body. However, changes to other physiological functions under such conditions have yet to be clarified. This study investigated changes in endocrine, inflammatory and immune parameters and individual differences during acute HH exposure using a climatic chamber (75 min of exposure to conditions mimicking 3500 m) in healthy lowlanders. Aldosterone and cortisol were significantly decreased and interleukin (IL)-6, IL-8 and white blood cell (WBC) counts were significantly increased after HH. Lower peripheral oxygen saturation (SpO2) was associated with higher IL-6 and WBC counts, and higher IL-8 was associated with higher cortisol. These findings suggest that endocrine, inflammatory and immune responses are evoked even with a short 75-min exposure to HH and individuals with lower SpO2 seemed to show more pronounced responses. Our results provide basic data for understanding the physiological responses and interactions of homeostatic systems during acute HH.
... The variables associated with mortality were, as expected: age, cancer, dementia, Charlson score, need for high-flow oxygen, including mechanical ventilation, and inflammatory markers (PCR, IL-9 6). These factors had been described in previous similar studies [11,[15][16][17][18][19]. The use of prophylactic LMWH was associated with lower mortality and this treatment is now strongly recommended in all COVID-19 hospitalized patients [20], but, as a limiting factor, we could not distinguish patients without prophylactic LMWH from those who received anticoagulated doses before or during admission, variables that are likely associated with different preexisting comorbidities and COVID-19 severity. ...
(1) Background: Since the onset of the SARS-CoV-2 pandemic, seven epidemic waves have been described in Spain. Our objective was to study mortality and severity, and associated factors in our hospitalized patients; (2) Method: Retrospective cohort study was conducted on COVID-19 patients admitted to the Hospital de Fuenlabrada (Madrid, Spain) from the beginning of the pandemic until December 31, 2022; (3) Results: A total of 5,510 admissions for COVID-19 were recorded. First wave accounted for 1,823 (33%) and exhibited the highest proportion of severe patients (lowest mean oxygen saturation, 88.2%; elevated levels of CRP, IL-6, D-dimer and ferri-tin), but a below-average percentage of intubated patients (5% vs. 6.5%). Overall mortality rate was 10.3%, higher during the first wave (11.5%) and the two winter waves (third: 11.3%, sixth: 12%), although the first wave represented 39% of the total. Variables associated with mortality were age (OR 1.08,1.07-1.09), need for high-flow oxygen (OR 6.10,4.94-7.52), oncological disease (OR 1.88,1.53-2.60), dementia (OR 1.82,1.2-2.75), Charlson index (OR 1.38,1.31-1.47), and maxi-mum IL-6 levels (OR 1.001,1.000-1.001); (4) Conclusions: Variables associated with mortality in-cluded age, comorbidity, respiratory failure, and inflammation. Differences on baseline charac-teristics of patients admitted explained differences on mortality in each wave
... Since IL6 is the main stimulator of cytokines, in addition to a potential treatment strategy targeting IL6, it might be employed independently as a biomarker in assessing the course of COVID-19 illness. [73] André Santa Cruz, et al. evaluated the association between IL-6 and the prognosis of patients with coronavirus illness. The cohort comprised of 46 adult patients with PCR-confirmed SARS-CoV-2 infection, whose IL-6 levels were monitored throughout time. ...
Since the outbreak of highly virulent coronaviruses, significant interest was assessed to the brain and heart axis (BHA) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-affected patients. The majority of clinical reports accounted for unusual symptoms associated with SARS-CoV-2 infections which are of the neurological type, such as headache, nausea, dysgeusia, anosmia, and cerebral infarction. The SARS-CoV-2 enters the cells through the angiotensin-converting enzyme (ACE-2) receptor. Patients with prior cardiovascular disease (CVD) have a higher risk of COVID-19 infection and it has related to various cardiovascular (CV) complications. Infected patients with pre-existing CVDs are also particularly exposed to critical health outcomes. Overall, COVID-19 affected patients admitted to intensive care units (ICU) and exposed to stressful environmental constraints, featured with a cluster of neurological and CV complications. In this review, we summarized the main contributions in the literature on how SARS-CoV-2 could interfere with the BHA and its role in affecting multiorgan disorders. Specifically, the central nervous system involvement, mainly in relation to CV alterations in COVID-19-affected patients, is considered. This review also emphasizes the biomarkers and therapy options for COVID-19 patients presenting with CV problems.
... The bioinformatics analysis of COVID-19 in the early stage has helped us to understand and speci c mechanism of the disease 18, 19 . Ghanem M had identi ed 17 different expressed proteins which showed a consistent change in other datasets and these genes were mainly enriched in in ammatory responses, platelet degranulation and neutrophil chemotaxis 20 . ...
Background
COVID-19 has spread all over the world which poses a serious threat to social economic development and public health. Despite enormous progress has been made in the prevention and treatment of COVID-19, the specific mechanism and biomarker related to disease severity or prognosis have not been clarified yet. Our study intended to further explore the diagnostic markers of COVID-19 and their relationship with serum immunology by bioinformatics analysis.
Methods
The datasets about COVID-19 were downloaded from the Gene Expression Omnibus (GEO) dataset. The differentially expressed genes (DEGs) were selected via the limma package. Then, weighted gene co-expression network analysis (WGCNA) was conducted to identify the critical module associated with the clinic status. The intersection DEGs were processed for further enrichment analysis. The final diagnostic genes for COVID-19 were selected and verified through special bioinformatics algorithms.
Results
There were significant DEGs between the normal and COVID-19 patients. These genes were mainly enriched in cell cycle, complement and coagulation cascade, extracellular matrix (ECM) receptor interaction, and the P53 signalling pathway. As much as 358 common intersected DEGs were selected in the end. These DEGs were enriched in organelle fission, mitotic cell cycle phase transition, DNA helicase activity, cell cycle, cellular senescence, and P53 signalling pathway. Our study also identified CDC25A, PDCD6, and YWAHE were potential diagnostic markers of COVID-19 with the AUC (area under curve), 0.958 (95% CI: 0.920–0.988), 0.941(95% CI: 0.892 − 0.980), and 0.929(95% CI: 0.880 − 0.971). Moreover, CDC25A, PDCD6, and YWAHE were correlated with plasma cells, macrophages M0, T cells CD4 memory resting, T cells CD8, dendritic cells, and NK cells.
Conclusions
Our study discovered that CDC25A, PDCD6 and YWAHE can be used as diagnostic markers for COVID-19. Moreover, these biomarkers were also closely associated with immune cell infiltration, which plays a pivotal role in the diagnosis and progression of COVID-19.
... COVID-19 is an infectious disease caused by SARS-CoV-2 that has reached pandemic proportions. Overactivated natural immunity and "cytokine storm" are considered to be the underlying pathological mechanisms for the rapid progression of COVID-19 [27]. Currently, the interaction between the two is not clear, but several studies have shown that the two are closely related. ...
Background
Severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 19 (COVID-19). The number of confirmed cases of COVID-19 is also rapidly increasing worldwide, posing a significant challenge to human safety. Asthma is a risk factor for COVID-19, but the underlying molecular mechanisms of the asthma–COVID-19 interaction remain unclear.
Methods
We used transcriptome analysis to discover molecular biomarkers common to asthma and COVID-19. Gene Expression Omnibus database RNA-seq datasets (GSE195599 and GSE196822) were used to identify differentially expressed genes (DEGs) in asthma and COVID-19 patients. After intersecting the differentially expressed mRNAs, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to identify the common pathogenic molecular mechanism. Bioinformatic methods were used to construct protein–protein interaction (PPI) networks and identify key genes from the networks. An online database was used to predict interactions between transcription factors and key genes. The differentially expressed long noncoding RNAs (lncRNAs) in the GSE195599 and GSE196822 datasets were intersected to construct a competing endogenous RNA (ceRNA) regulatory network. Interaction networks were constructed for key genes with RNA-binding proteins (RBPs) and oxidative stress-related proteins. The diagnostic efficacy of key genes in COVID-19 was verified with the GSE171110 dataset. The differential expression of key genes in asthma was verified with the GSE69683 dataset. An asthma cell model was established with interleukins (IL-4, IL-13 and IL-17A) and transfected with siRNA-CXCR1. The role of CXCR1 in asthma development was preliminarily confirmed.
Results
By intersecting the differentially expressed genes for COVID-19 and asthma, 393 common DEGs were obtained. GO and KEGG enrichment analyses of the DEGs showed that they mainly affected inflammation-, cytokine- and immune-related functions and inflammation-related signaling pathways. By analyzing the PPI network, we obtained 10 key genes: TLR4, TLR2, MMP9, EGF, HCK, FCGR2A, SELP, NFKBIA, CXCR1, and SELL. By intersecting the differentially expressed lncRNAs for COVID-19 and asthma, 13 common differentially expressed lncRNAs were obtained. LncRNAs that regulated microRNAs (miRNAs) were mainly concentrated in intercellular signal transduction, apoptosis, immunity and other related functional pathways. The ceRNA network suggested that there were a variety of regulatory miRNAs and lncRNAs upstream of the key genes. The key genes could also bind a variety of RBPs and oxidative stress-related genes. The key genes also had good diagnostic value in the verification set. In the validation set, the expression of key genes was statistically significant in both the COVID-19 group and the asthma group compared with the healthy control group. CXCR1 expression was upregulated in asthma cell models, and interference with CXCR1 expression significantly reduced cell viability.
Conclusions
Key genes may become diagnostic and predictive biomarkers of outcomes in COVID-19 and asthma.
... In a recent meta-analysis, IL-6 was identified as a master regulator of COVID-19 severity biomarkers such as IL-10, CRP, fibrinogen, and alpha-1-antichymotrypsin (SERPINA3), Suggesting that it could be a potential independent marker for COVID-19 disease progression and a promising treatment target [9]. In addition to laboratory findings, Xue et al. also showed that elevated IL-6 concentrations are also a risk factor for prolonged clearance time of SARS-CoV-2 [10]. ...
The COVID-19 pandemic has reinforced an interest in the relationship between air pollution and respiratory viral infections, indicating that their burden can be increased under poor air quality. This paper reviews the pathways through which air pollutants can enhance susceptibility to such infections and aggravate their clinical course and outcome. It also summarizes the research exploring the links between various viral infections and exposure to solid and gaseous pollution in Poland, a region characterized by poor air quality, especially during a heating season. The majority of studies focused on concentrations of PM (86.7%); the other pollutants, i.e., BaP, benzene, CO, NOx, O3, and SO2, were studied less often and sometimes only in the context of a particular infection type. Most research concerned COVID-19, showing that elevated levels of particulate matter (PM) and NO2 correlated with higher morbidity and mortality, while increased PM2.5 and benzo[a]pyrene levels were related to worse clinical course and outcome in hospitalized, regardless of age and dominant SARS-CoV-2 variant. PM10 and PM2.5 levels were also associated with the incidence of influenza-like illness and, along with NO2 concentrations, with a higher rate of children's hospitalizations due to lower respiratory tract RSV infections. Higher levels of air pollutants also increased hospitalization due to bronchitis (PM, NOx, and O3) and emergency department admission due to viral croup (PM10, PM2.5, NOx, CO, and benzene). Although the conducted studies imply only correlations and have other limitations, as discussed in the present paper, it appears that improving air quality through reducing combustion processes in energy production in Poland should be perceived as a part of multilayered protection measures against respiratory viral infections, decreasing the healthcare costs of COVID-19, lower tract RSV infections, influenza, and other respiratory viral diseases prevalent between autumn and early spring, in addition to other health and climate benefits.
