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

Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes severe COVID-19 in some patients and mild COVID-19 in others. Dysfunctional innate immune responses have been identified to contribute to COVID-19 severity, but the key regulators are still unknown. Here, we prese...

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Main Authors: Bowen Zhang (Author), Zhenhua Zhang (Author), Valerie A.C.M. Koeken (Author), Saumya Kumar (Author), Michelle Aillaud (Author), Hsin-Chieh Tsay (Author), Zhaoli Liu (Author), Anke R.M. Kraft (Author), Chai Fen Soon (Author), Ivan Odak (Author), Berislav Bošnjak (Author), Anna Vlot (Author), Morris A. Swertz (Author), Uwe Ohler (Author), Robert Geffers (Author), Thomas Illig (Author), Jochen Huehn (Author), Antoine-Emmanuel Saliba (Author), Leif Erik Sander (Author), Reinhold Förster (Author), Cheng-Jian Xu (Author), Markus Cornberg (Author), Leon N. Schulte (Author), Yang Li (Author)
Format: Book
Published: Elsevier, 2023-02-01T00:00:00Z.
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Summary:Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes severe COVID-19 in some patients and mild COVID-19 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 revealed 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.
Item Description:2666-979X
10.1016/j.xgen.2022.100232

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