Blood DNA Methylation Biomarkers of Post AcuteSequelae of SARS CoV 2 Infection (PASC)

NIH Pandemic-Era Grants

Pandemic Era Grants

2023

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Principal Investigator: Reid Spencer Alisch
Organization: ALBANY MEDICAL COLLEGE
Fiscal Year: 2023
Award: $812,430
Funding agency: National Institute of Allergy and Infectious Diseases

Project Summary: DNA 5'-C-phosphate-G-3' (CpG) methylation is a covalent epigenetic modification that
regulates gene expression and is highly sensitive to age and environmental factors. Critically ill patients exhibit
altered circulating blood DNA methylation profiles. We have recently reported a large scale methylome analysis
of COVID-19 in association with clinical outcomes, which suggests an epigenetic regulation of genes controlling
disease severity. Recent evidence indicates that many surviving COVID-19 patients develop long term
dysfunctions and the NIH-NHLBI has recently launched an initiative to elucidate the nature of Post-Acute
Sequelae of SARS-CoV-2 Infection (PASC). It is currently unknown if the rapid methylome regulation evoked by
acute illness persist after SARS-CoV-2 resolution. Such persistence could underpin long term sequela
associated with this condition. Because DNA methylation is a relatively stable DNA chemical modification that
could influence long-term gene expression profiles and given that we recently found that multiple regions
developed during acute illness persist differentially methylated one year after hospital discharge, we
hypothesize that COVID-19 infection leads to enduring DNA methylation abnormalities that remain after
resolution of acute illness in association with the post-COVID-19 clinical profile. In this application, we
plan to conduct whole genome DNA methylation and RNA sequencing of circulating leucocytes to establish sub
phenotypes of PASC, predict future PASC development in the acute COVID-19, and determine which circulating
leucocyte lineage contributes to that enduring methylome.

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life><Chemicals><Classification><Clinical><CoV-2><CoV2><Cognitive><Critical Illness><Critically Ill><DNA><DNA Maintenance><DNA Methylation><DNA Stability><DNA methylation profiling><DNA seq><DNA sequencing><DNAseq><Data><Death><Deoxyribonucleic Acid><Development><Dimensions><Dysfunction><Dyspnea><Environmental Factor><Environmental Risk Factor><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Exhibits><Functional RNA><Functional disorder><Future><Gene Action Regulation><Gene Expression><Gene Expression Regulation><Gene Regulation><Gene Regulation Process><Genomics><Hospital Admission><Hospitalization><Hospitals><Host Factor><Host Factor Protein><Immune><Immunes><Individual><Inflammatory><Integration Host Factors><Leukocytes><Leukocytes Reticuloendothelial System><Long COVID><Long COVID-19><Long coronavirus disease><Long coronavirus disease 2019><Lymphoid><Lymphoid Cell><Magnetism><Marrow leukocyte><Measures><Methyl-Seq><MethylSeq><Methylation><Methylation sequencing><Mission><Modification><Molecular><Muscle Weakness><Muscular Weakness><Myelogenous><Myeloid><Myeloid Cells><NHLBI><NIH><National Heart, Lung, and Blood Institute><National Institutes of Health><Nature><Non-Coding><Non-Coding RNA><Non-Polyadenylated RNA><Non-translated RNA><Noncoding RNA><Nontranslated RNA><Outcome><PASC><Participant><Patients><Pattern><Phenotype><Phosphates><Physiopathology><Population><Position><Positioning Attribute><Post Acute Sequelae of COVID19><Post Acute Sequelae of SARS-CoV-2><Post Acute Sequelae of SARS-CoV2><Post Acute Sequelae of severe acute respiratory syndrome coronavirus 2><Post-Acute Sequelae of SARS-CoV-2 Infection><Predisposition><Process><Public Health><Publishing><RNA><RNA Gene Products><RNA Seq><RNA Sequences><RNA sequencing><RNAseq><Recovery><Regulation><Reporting><Research><Resolution><Ribonucleic Acid><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 disease severity><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 severity><SARS-CoV-2 survivors><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Sensitivity and Specificity><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome related corona virus 2><Severity of illness><Sleep Disorders><Subgroup><Susceptibility><Systematics><Testing><Time><Tissues><Transcript><United States National Institutes of Health><Untranslated RNA><White Blood Cells><White Cell><Wuhan coronavirus><acute infection><adverse sequelae of COVID><adverse sequelae of COVID-19><adverse sequelae of coronavirus disease><adverse sequelae of coronavirus disease 2019><after COVID-19 infection><after SARS-CoV-2 infection><after SARS-CoV2 infection><after infection by SARS-CoV-2><after severe acute respiratory distress syndrome CoV-2 infection><analyzing longitudinal><burden of infection><cell sorting><chromatin modification><chronic COVID><chronic COVID-19><chronic COVID-19 sequelae><chronic novel coronavirus disease 2019><clinical phenotype><corona virus disease 2019><coronavirus disease 2019><coronavirus disease 2019 consequence><coronavirus disease 2019 disease severity><coronavirus disease 2019 effect><coronavirus disease 2019 impact><coronavirus disease 2019 infected patient><coronavirus disease 2019 infection><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 severity><coronavirus disease 2019 virus><coronavirus disease infected patient><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease severity><coronavirus disease-19><coronavirus disease-19 impact><coronavirus disease-19 patient><coronavirus disease-19 virus><coronavirus infectious disease-19><coronavirus patient><developmental><disease control><disease severity><disorder control><entire genome><environmental risk><epigenetic regulation><epigenetically><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following infection by SARS-CoV-2><following severe acute respiratory distress syndrome CoV-2 infection><full genome><genome scale><genome-wide><genomewide><global gene expression><global transcription profile><hCoV19><histone modification><individual response><individualized response><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><infection burden><inorganic phosphate><instrument><long haul COVID><long haul COVID-19><long haul coronavirus disease><long haul coronavirus disease 2019><long haul sequelae of COVID-19><long haul sequelae of coronavirus disease 2019><long-hauler COVID><long-hauler COVID-19><long-hauler coronavirus disease 2019><long-hauler syndrome><long-term COVID><long-term COVID-19><long-term coronavirus disease><long-term coronavirus disease 2019><long-term sequelae><long-term sequelae of COVID-19><long-term sequelae of SARS-CoV-2><long-term sequelae of coronavirus disease 2019><long-term sequelae of severe acute respiratory syndrome coronavirus 2><longitudinal analysis><longterm COVID><longterm COVID-19><longterm coronavirus disease><longterm coronavirus disease 2019><machine learning based classification><machine learning classification><magnetic><methylation biomarker><methylation marker><methylome><multiomics><multiple omics><nCoV2><noncoding><novel><pathophysiology><patient infected with COVID><patient infected with COVID-19><patient infected with SARS-CoV-2><patient infected with coronavirus disease><patient infected with coronavirus disease 2019><patient infected with severe acute respiratory syndrome coronavirus 2><patient with COVID><patient with COVID-19><patient with COVID19><patient with SARS-CoV-2><patient with coronavirus disease><patient with coronavirus disease 2019><patient with severe acute respiratory distress syndrome coronavirus 2><post COVID syndrome><post COVID-19 syndrome><post SARS-CoV-2 infection><post acute COVID syndrome><post acute COVID-19><post acute COVID-19 syndrome><post acute SARS-CoV-2><post acute coronavirus disease 2019><post acute coronavirus disease 2019 syndrome><post acute coronavirus disease syndrome><post acute severe acute respiratory syndrome coronavirus 2><post coronavirus disease 2019 syndrome><post coronavirus disease syndrome><post-COVID><post-COVID-19><post-acute phases of COVID-19><post-acute sequelae following SARS-CoV-2 infection><post-acute sequelae of COVID-19><post-acute sequelae of acute COVID infection><post-acute sequelae of coronavirus disease 2019><post-coronavirus disease 2019><previous COVID-19 infection><previous SARS-CoV-2 infection><previous SARS-CoV2 infection><previous severe acute respiratory distress syndrome CoV-2 infection><prior COVID-19 infection><prior SARS-CoV-2 infection><prior SARS-CoV2 infection><prior severe acute respiratory distress syndrome CoV-2 infection><resolutions><severe acute respiratory syndrome coronavirus 2 disease severity><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><severe acute respiratory syndrome coronavirus 2 severity><sleep diseases><sleep dysfunction><sleep illness><sleep problem><survive COVID-19><survive SARS-CoV-2><transcriptome><transcriptome sequencing><transcriptomic sequencing><white blood cell><white blood corpuscle><whole genome>