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Chromatin remodeling in peripheral blood cells reflects COVID-19 symptom severity
Nicholas S. Giroux; Shengli Ding; Micah T. McClain; Thomas W. Burke; Elizabeth W. Petzold; Hong A. Chung; Grecia R. Palomino; Ergang Wang; Rui Xi; Shree Bose; Tomer Rotstein; Bradly P. Nicholson; Tianyi Chen; Ricardo Henao; Gregory D. Sempowski; Thomas N. Denny; Emily R. Ko; Geoffrey S. Ginsburg; Bryan D. Kraft; Ephraim L. Tsalik; Christopher W. Woods; Xiling Shen.
Affiliation
  • Nicholas S. Giroux; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA
  • Shengli Ding; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA
  • Micah T. McClain; Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA
  • Thomas W. Burke; Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA
  • Elizabeth W. Petzold; Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA
  • Hong A. Chung; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA
  • Grecia R. Palomino; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA
  • Ergang Wang; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA
  • Rui Xi; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA
  • Shree Bose; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA
  • Tomer Rotstein; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA
  • Bradly P. Nicholson; Institute for Medical Research, Durham, NC, USA
  • Tianyi Chen; Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC, USA
  • Ricardo Henao; Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA
  • Gregory D. Sempowski; Duke Human Vaccine Institute and Department of Medicine, School of Medicine, Duke University, Durham, NC, USA
  • Thomas N. Denny; Duke Human Vaccine Institute and Department of Medicine, School of Medicine, Duke University, Durham, NC, USA
  • Emily R. Ko; Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA
  • Geoffrey S. Ginsburg; Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA
  • Bryan D. Kraft; Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA
  • Ephraim L. Tsalik; Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, USA
  • Christopher W. Woods; Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA
  • Xiling Shen; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA
Preprint in En | PREPRINT-BIORXIV | ID: ppbiorxiv-412155
ABSTRACT
SARS-CoV-2 infection triggers highly variable host responses and causes varying degrees of illness in humans. We sought to harness the peripheral blood mononuclear cell (PBMC) response over the course of illness to provide insight into COVID-19 physiology. We analyzed PBMCs from subjects with variable symptom severity at different stages of clinical illness before and after IgG seroconversion to SARS-CoV-2. Prior to seroconversion, PBMC transcriptomes did not distinguish symptom severity. In contrast, changes in chromatin accessibility were associated with symptom severity. Furthermore, single-cell analyses revealed evolution of the chromatin accessibility landscape and transcription factor motif occupancy for individual PBMC cell types. The most extensive remodeling occurred in CD14+ monocytes where sub-populations with distinct chromatin accessibility profiles were associated with disease severity. Our findings indicate that pre-seroconversion chromatin remodeling in certain innate immune populations is associated with divergence in symptom severity, and the identified transcription factors, regulatory elements, and downstream pathways provide potential prognostic markers for COVID-19 subjects. One sentence summaryChromatin accessibility in immune cells from COVID-19 subjects is remodeled prior to seroconversion to reflect disease severity.
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Full text: 1 Collection: 09-preprints Database: PREPRINT-BIORXIV Type of study: Experimental_studies / Prognostic_studies Language: En Year: 2020 Type: Preprint
Fulltext
Print
XML
Search on Google
Full text: 1 Collection: 09-preprints Database: PREPRINT-BIORXIV Type of study: Experimental_studies / Prognostic_studies Language: En Year: 2020 Type: Preprint