Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion.
| dc.contributor.author | Giroux, Nicholas S | |
| dc.contributor.author | Ding, Shengli | |
| dc.contributor.author | McClain, Micah T | |
| dc.contributor.author | Burke, Thomas W | |
| dc.contributor.author | Petzold, Elizabeth | |
| dc.contributor.author | Chung, Hong A | |
| dc.contributor.author | Rivera, Grecia O | |
| dc.contributor.author | Wang, Ergang | |
| dc.contributor.author | Xi, Rui | |
| dc.contributor.author | Bose, Shree | |
| dc.contributor.author | Rotstein, Tomer | |
| dc.contributor.author | Nicholson, Bradly P | |
| dc.contributor.author | Chen, Tianyi | |
| dc.contributor.author | Henao, Ricardo | |
| dc.contributor.author | Sempowski, Gregory D | |
| dc.contributor.author | Denny, Thomas N | |
| dc.contributor.author | De Ussel, Maria Iglesias | |
| dc.contributor.author | Satterwhite, Lisa L | |
| dc.contributor.author | Ko, Emily R | |
| dc.contributor.author | Ginsburg, Geoffrey S | |
| dc.contributor.author | Kraft, Bryan D | |
| dc.contributor.author | Tsalik, Ephraim L | |
| dc.contributor.author | Shen, Xiling | |
| dc.contributor.author | Woods, Christopher W | |
| dc.date.accessioned | 2022-08-08T16:43:21Z | |
| dc.date.available | 2022-08-08T16:43:21Z | |
| dc.date.issued | 2022-07-09 | |
| dc.date.updated | 2022-08-08T16:43:20Z | |
| dc.description.abstract | SARS-CoV-2 infection triggers profound and variable immune responses in human hosts. Chromatin remodeling has been observed in individuals severely ill or convalescing with COVID-19, but chromatin remodeling early in disease prior to anti-spike protein IgG seroconversion has not been defined. We performed the Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) and RNA-seq on peripheral blood mononuclear cells (PBMCs) from outpatients with mild or moderate symptom severity at different stages of clinical illness. Early in the disease course prior to IgG seroconversion, modifications in chromatin accessibility associated with mild or moderate symptoms were already robust and included severity-associated changes in accessibility of genes in interleukin signaling, regulation of cell differentiation and cell morphology. Furthermore, single-cell analyses revealed evolution of the chromatin accessibility landscape and transcription factor motif accessibility for individual PBMC cell types over time. The most extensive remodeling occurred in CD14+ monocytes, where sub-populations with distinct chromatin accessibility profiles were observed prior to seroconversion. Mild symptom severity was marked by upregulation of classical antiviral pathways, including those regulating IRF1 and IRF7, whereas in moderate disease, these classical antiviral signals diminished, suggesting dysregulated and less effective responses. Together, these observations offer novel insight into the epigenome of early mild SARS-CoV-2 infection and suggest that detection of chromatin remodeling in early disease may offer promise for a new class of diagnostic tools for COVID-19. | |
| dc.identifier | 10.1038/s41598-022-15668-8 | |
| dc.identifier.issn | 2045-2322 | |
| dc.identifier.issn | 2045-2322 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Springer Science and Business Media LLC | |
| dc.relation.ispartof | Scientific reports | |
| dc.relation.isversionof | 10.1038/s41598-022-15668-8 | |
| dc.subject | Leukocytes, Mononuclear | |
| dc.subject | Chromatin | |
| dc.subject | Humans | |
| dc.subject | Immunoglobulin G | |
| dc.subject | Antiviral Agents | |
| dc.subject | Severity of Illness Index | |
| dc.subject | Seroconversion | |
| dc.subject | COVID-19 | |
| dc.subject | SARS-CoV-2 | |
| dc.title | Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Giroux, Nicholas S|0000-0003-3801-4689 | |
| duke.contributor.orcid | Sempowski, Gregory D|0000-0003-0391-6594 | |
| duke.contributor.orcid | Ginsburg, Geoffrey S|0000-0003-4739-9808 | |
| duke.contributor.orcid | Tsalik, Ephraim L|0000-0002-6417-2042 | |
| duke.contributor.orcid | Shen, Xiling|0000-0002-4978-3531 | |
| duke.contributor.orcid | Woods, Christopher W|0000-0001-7240-2453 | |
| pubs.begin-page | 11714 | |
| pubs.issue | 1 | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Pratt School of Engineering | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Faculty | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Institutes and Centers | |
| pubs.organisational-group | Civil and Environmental Engineering | |
| pubs.organisational-group | Medicine | |
| pubs.organisational-group | Pathology | |
| pubs.organisational-group | Medicine, Duke Human Vaccine Institute | |
| pubs.organisational-group | Medicine, Infectious Diseases | |
| pubs.organisational-group | Medicine, Pulmonary, Allergy, and Critical Care Medicine | |
| pubs.organisational-group | Duke Human Vaccine Institute | |
| pubs.organisational-group | Institutes and Provost's Academic Units | |
| pubs.organisational-group | University Institutes and Centers | |
| pubs.organisational-group | Duke Global Health Institute | |
| pubs.organisational-group | Duke Institute for Brain Sciences | |
| pubs.organisational-group | Duke Center for Applied Genomics and Precision Medicine | |
| pubs.publication-status | Published | |
| pubs.volume | 12 |