Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection
Micah T. McClain,
Ilya Zhbannikov,
Lisa L. Satterwhite,
Ricardo Henao,
Nicholas S. Giroux,
Shengli Ding,
Thomas W. Burke,
Ephraim L. Tsalik,
Christina Nix,
Jorge Prado Balcazar,
Elizabeth A. Petzold,
Xiling Shen,
Christopher W. Woods
Affiliations
Micah T. McClain
Division of Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA; Durham Veterans Affairs Medical Center, Durham, NC 27705, USA; Corresponding author
Ilya Zhbannikov
Department of Medicine, Clinical Research Unit, Duke University Medical Center, Durham, NC 27710, USA
Lisa L. Satterwhite
Department of Civil and Environmental Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA
Ricardo Henao
Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC 27710, USA
Nicholas S. Giroux
Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA
Shengli Ding
Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA
Thomas W. Burke
Division of Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA
Ephraim L. Tsalik
Danaher Diagnostics, Washington, DC 20037, USA
Christina Nix
Division of Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA
Jorge Prado Balcazar
Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA
Elizabeth A. Petzold
Division of Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA
Xiling Shen
Terasaki Institute for Biological Innovation, Los Angeles, CA 90024, USA
Christopher W. Woods
Division of Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA; Durham Veterans Affairs Medical Center, Durham, NC 27705, USA
Summary: To elucidate host response elements that define impending decompensation during SARS-CoV-2 infection, we enrolled subjects hospitalized with COVID-19 who were matched for disease severity and comorbidities at the time of admission. We performed combined single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) on peripheral blood mononuclear cells (PBMCs) at admission and compared subjects who improved from their moderate disease with those who later clinically decompensated and required invasive mechanical ventilation or died. Chromatin accessibility and transcriptomic immune profiles were markedly altered between the two groups, with strong signals in CD4+ T cells, inflammatory T cells, dendritic cells, and NK cells. Multiomic signature scores at admission were tightly associated with future clinical deterioration (auROC 1.0). Epigenetic and transcriptional changes in PBMCs reveal early, broad immune dysregulation before typical clinical signs of decompensation are apparent and thus may act as biomarkers to predict future severity in COVID-19.
