ABSTRACT
Variations in DNA methylation patterns in human tissues have been linked to various environmental exposures and infections. Here, we identified the DNA methylation signatures associated with multiple exposures in nine major immune cell types derived from peripheral blood mononuclear cells (PBMCs) at single-cell resolution. We performed methylome sequencing on 111,180 immune cells obtained from 112 individuals who were exposed to different viruses, bacteria, or chemicals. Our analysis revealed 790,662 differentially methylated regions (DMRs) associated with these exposures, which are mostly individual CpG sites. Additionally, we integrated methylation and ATAC-seq data from same samples and found strong correlations between the two modalities. However, the epigenomic remodeling in these two modalities are complementary. Finally, we identified the minimum set of DMRs that can predict exposures. Overall, our study provides the first comprehensive dataset of single immune cell methylation profiles, along with unique methylation biomarkers for various biological and chemical exposures.
ABSTRACT
Our understanding of protective vs. pathologic immune responses to SARS-CoV-2, the virus that causes Coronavirus disease 2019 (COVID-19), is limited by inadequate profiling of patients at the extremes of the disease severity spectrum. Here, we performed multi-omic single-cell immune profiling of 64 COVID-19 patients across the full range of disease severity, from outpatients with mild disease to fatal cases. Our transcriptomic, epigenomic, and proteomic analyses reveal widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19, with the most profound disturbances including a prominent neutrophil hyperactivation signature and monocytes with anti-inflammatory features. We further demonstrate that emergency myelopoiesis is a prominent feature of fatal COVID-19. Collectively, our results reveal disease severity-associated immune phenotypes in COVID-19 and identify pathogenesis-associated pathways that are potential targets for therapeutic intervention.
Subject(s)
COVID-19ABSTRACT
Since the first identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China in late December 2019, the coronavirus disease 2019 (COVID-19) has spread fast around the world. RNA viruses, including SARS-CoV-2, have higher gene mutations than DNA viruses during virus replication. Variations in SARS-CoV-2 genome could contribute to efficiency of viral spread and severity of COVID-19. In this study, we analyzed the locations of genomic mutations to investigate the genetic diversity among isolates of SARS-CoV-2 in Gwangju. We detected non-synonymous and frameshift mutations in various parts of SARS-CoV-2 genome. The phylogenetic analysis for whole genome showed that SARS-CoV-2 genomes in Gwangju isolates are clustered within clade V and G. Our findings not only provide a glimpse into changes of prevalent virus clades in Gwangju, South Korea, but also support genomic surveillance of SARS-CoV-2 to aid in the development of efficient therapeutic antibodies and vaccines against COVID-19.