Altered and allele-specific open chromatin landscape reveals epigenetic and genetic regulators of innate immunity in COVID-19


  • B. Zhang
  • Z. Zhang
  • V.A.C.M. Koeken
  • S. Kumar
  • M. Aillaud
  • H.C. Tsay
  • Z. Liu
  • A.R.M. Kraft
  • C.F. Soon
  • I. Odak
  • B. Bošnjak
  • A. Vlot
  • M.A. Swertz
  • U. Ohler
  • R. Geffers
  • T. Illig
  • J. Huehn
  • A.E. Saliba
  • L.E. Sander
  • R. Förster
  • C.J. Xu
  • M. Cornberg
  • L.N. Schulte
  • Y. Li


  • Cell Genomics


  • Cell Genom 3 (2): 100232


  • SARS-CoV-2 infection causes severe COVID-19 in some patients and mild in others. Dysfunctional innate immune responses have been identified to contribute to COVID-19 severity, but the key regulators are still unknown. Here, we present an integrative single-cell multi-omics analysis of peripheral blood mononuclear cells from hospitalized and convalescent COVID-19 patients. In classical monocytes, we identified genes that were potentially regulated by differential chromatin accessibility. Then, sub-clustering and motif-enrichment analyses reveals disease condition-specific regulation by transcription factors and their targets, including an interaction between (C/EBPs) and a long-noncoding RNA (LUCAT1), which we validated through loss-of-function experiments. Finally, we investigated genetic risk variants that exhibit allele-specific open chromatin (AsoC) in COVID-19 patients and identified a SNP rs6800484-C, which is associated with lower expression of (CCR2) and may contribute to higher viral loads and higher risk of COVID-19 hospitalization. Altogether, our study highlights the diverse genetic and epigenetic regulators that contribute to COVID-19.