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