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dc.contributor.authorSadanandam, A
dc.contributor.authorBopp, T
dc.contributor.authorDixit, S
dc.contributor.authorKnapp, DJHF
dc.contributor.authorEmperumal, CP
dc.contributor.authorVergidis, P
dc.contributor.authorRajalingam, K
dc.contributor.authorMelcher, A
dc.contributor.authorKannan, N
dc.date.accessioned2021-03-02T16:07:29Z
dc.date.available2021-03-02T16:07:29Z
dc.date.issued2020-12-08
dc.identifier.citationCell death discovery, 2020, 6 (1), pp. 141 - ?
dc.identifier.issn2058-7716
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4387
dc.identifier.eissn2058-7716
dc.identifier.doi10.1038/s41420-020-00376-x
dc.description.abstractCOVID-19 patients show heterogeneity in clinical presentation and outcomes that makes pandemic control and strategy difficult; optimizing management requires a systems biology approach of understanding the disease. Here we sought to potentially understand and infer complex disease progression, immune regulation, and symptoms in patients infected with coronaviruses (35 SARS-CoV and 3 SARS-CoV-2 patients and 57 samples) at two different disease progression stages. Further, we compared coronavirus data with healthy individuals (n = 16) and patients with other infections (n = 144; all publicly available data). We applied inferential statistics (the COVID-engine platform) to RNA profiles (from limited number of samples) derived from peripheral blood mononuclear cells (PBMCs). Compared to healthy individuals, a subset of integrated blood-based gene profiles (signatures) distinguished acute-like (mimicking coronavirus-infected patients with prolonged hospitalization) from recovering-like patients. These signatures also hierarchically represented multiple (at the system level) parameters associated with PBMC including dysregulated cytokines, genes, pathways, networks of pathways/concepts, immune status, and cell types. Proof-of-principle observations included PBMC-based increases in cytokine storm-associated IL6, enhanced innate immunity (macrophages and neutrophils), and lower adaptive T and B cell immunity in patients with acute-like disease compared to those with recovery-like disease. Patients in the recovery-like stage showed significantly enhanced TNF, IFN-γ, anti-viral, HLA-DQA1, and HLA-F gene expression and cytolytic activity, and reduced pro-viral gene expression compared to those in the acute-like stage in PBMC. Besides, our analysis revealed overlapping genes associated with potential comorbidities (associated diabetes) and disease-like conditions (associated with thromboembolism, pneumonia, lung disease, and septicemia). Overall, our COVID-engine inferential statistics platform and study involving PBMC-based RNA profiling may help understand complex and variable system-wide responses displayed by coronavirus-infected patients with further validation.
dc.formatElectronic
dc.format.extent141 - ?
dc.languageeng
dc.language.isoeng
dc.publisherSPRINGERNATURE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleA blood transcriptome-based analysis of disease progression, immune regulation, and symptoms in coronavirus-infected patients.
dc.typeJournal Article
dcterms.dateAccepted2020-11-13
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41420-020-00376-x
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-12-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCell death discovery
pubs.issue1
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine
pubs.publication-statusPublished
pubs.volume6
pubs.embargo.termsNot known
icr.researchteamSystems and Precision Cancer Medicine
icr.researchteamSystems and Precision Cancer Medicine
dc.contributor.icrauthorMelcher, Alan


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