Diagnostics & Biomarkers
DETECTING, PREDICTING SEVERITY OF, AND/OR PREDICTING TREATMENT RESPONSE TO RESPIRATORY VIRUS INFECTION
WARF: P210192US02
Inventors: Reid Alisch, Kirk Hogan, Andy Madrid, Ariel Jaitovich
The Invention
Using two sets of comparative patient samples (hospitalized COVID-19 patients vs controls from 3 years ago, and hospitalized COVID-19 patients vs patients hospitalized for other conditions), the inventors identified differentially DNA methylated regions (DMRs) and differentially methylated positions (DMPs) that predict COVID-19 severity, prognosis, and outcomes.
Differentially DNA methylated regions (DMRs) comprising 5 or more consecutively hyper-methylated or hypo-methylated CpGs were compared between blood samples from patients admitted for management of COVID-19, and samples from participants collected 3 years before the SARS-Cov-2 pandemic, using the Illumina Infinium Methylation EPIC Array. 1089 hypo-methylated DMRs (63%) and 416 hyper-methylated DMRs (38%) distinguished patients with COVID-19 within days of infection with extraordinary statistical significance. The preponderance of DMRs were observed in gene promoter regions. Gene ontology analysis indicates that the DMRs occur in genes that participate in white blood cell activation and immune responsivity. Disease ontology analysis indicates that the DMRs occur in genes that participate in the pathogenesis of inflammatory and white blood cell disorders.
DMRs were further compared between patients admitted for COVID-19 and patients admitted with non-COVID-19 respiratory illness. Gene ontology analysis of loci comprising 254 DMRs that distinguish the 2 hospitalized cohorts indicates that the DMRs occur in genes that participate in inflammatory and host defense pathways. Gene disease analysis indicates that the DMRs occur in genes that participate in the pathogenesis of inflammation, other viral infections, and autoimmune disorders. 47 DMRs that overlap between the 2 comparisons occur in genes that encode white blood cell viral defense constituents including interferon stimulated genes (ISN), inflammation and immune responsivity. Among COVID-19 patients, a more severe GRAM severity score on admission and overall mortality were associated with hyper-methylated DMRs. Recursive feature elimination identified differentially methylated positions (DMPs) that predict COVID-19 severity, prognosis and outcomes.
Differentially DNA methylated regions (DMRs) comprising 5 or more consecutively hyper-methylated or hypo-methylated CpGs were compared between blood samples from patients admitted for management of COVID-19, and samples from participants collected 3 years before the SARS-Cov-2 pandemic, using the Illumina Infinium Methylation EPIC Array. 1089 hypo-methylated DMRs (63%) and 416 hyper-methylated DMRs (38%) distinguished patients with COVID-19 within days of infection with extraordinary statistical significance. The preponderance of DMRs were observed in gene promoter regions. Gene ontology analysis indicates that the DMRs occur in genes that participate in white blood cell activation and immune responsivity. Disease ontology analysis indicates that the DMRs occur in genes that participate in the pathogenesis of inflammatory and white blood cell disorders.
DMRs were further compared between patients admitted for COVID-19 and patients admitted with non-COVID-19 respiratory illness. Gene ontology analysis of loci comprising 254 DMRs that distinguish the 2 hospitalized cohorts indicates that the DMRs occur in genes that participate in inflammatory and host defense pathways. Gene disease analysis indicates that the DMRs occur in genes that participate in the pathogenesis of inflammation, other viral infections, and autoimmune disorders. 47 DMRs that overlap between the 2 comparisons occur in genes that encode white blood cell viral defense constituents including interferon stimulated genes (ISN), inflammation and immune responsivity. Among COVID-19 patients, a more severe GRAM severity score on admission and overall mortality were associated with hyper-methylated DMRs. Recursive feature elimination identified differentially methylated positions (DMPs) that predict COVID-19 severity, prognosis and outcomes.
Additional Information
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Tech Fields
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