Epigenetic Memory of COVID-19 in Innate Immune Cells and Their Progenitors

Cheong, J. G.; Ravishankar, A.; Sharma, S.; Parkhurst, C.; Nehar-Belaid, D.; Ma, S.; Paddock, L.; Fatou, B.; Karakaslar, E.; Thibodeau, A.; Bale, M.; Kartha, V.; Yee, J.; Mays, M. Y.; Leyre, L.; Martinez de Paz, A.; Daman, A.; Alvarez-Mulett, S.; Robbins, L.; LaFond, E.; Weidman, K.; Racine-Brzostek, S.; Yang, H.; Price, D.; Jones, R. B.; Schenck, E.; Kaner, R.; Chadburn, A.; Zhao, Z.; Steen, H.; Pascual, V.; Buenrostro, J.; Niec, R.; Lief, L.; Ucar, D.; Josefowicz, S.

doi:10.1101/2022.02.09.479588

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bioRxiv · 10.1101/2022.02.09.479588

Epigenetic Memory of COVID-19 in Innate Immune Cells and Their Progenitors

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Abstract

Severe coronavirus disease 2019 (COVID-19) is characterized by systemic inflammation and can result in protracted symptoms. Robust systemic inflammation may trigger persistent changes in hematopoietic cells and innate immune memory through epigenetic mechanisms. We reveal that rare circulating hematopoietic stem and progenitor cells (HSPC), enriched from human blood, match the diversity of HSPC in bone marrow, enabling investigation of hematopoiesis and HSPC epigenomics. Following COVID-19, HSPC retain epigenomic alterations that are conveyed, through differentiation, to progeny innate immune cells. Epigenomic changes vary with disease severity, persist for months to a year, and are associated with increased myeloid cell differentiation and inflammatory or antiviral programs. Epigenetic reprogramming of HSPC may underly altered immune function following infection and be broadly relevant, especially for millions of COVID-19 survivors. One Sentence SummaryTranscriptomic and epigenomic analysis of blood reveal sustained changes in hematopoiesis and innate immunity after COVID-19. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=197 HEIGHT=200 SRC="FIGDIR/small/479588v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@1ffe42dorg.highwire.dtl.DTLVardef@dd4868org.highwire.dtl.DTLVardef@1bcae8borg.highwire.dtl.DTLVardef@674e85_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Cheong, J. G., Ravishankar, A., Sharma, S., Parkhurst, C., Nehar-Belaid, D., Ma, S., Paddock, L., Fatou, B., Karakaslar, E., Thibodeau, A., Bale, M., Kartha, V., Yee, J., Mays, M. Y., Leyre, L., Martinez de Paz, A., Daman, A., Alvarez-Mulett, S., Robbins, L., LaFond, E., Weidman, K., Racine-Brzostek, S., Yang, H., Price, D., Jones, R. B., Schenck, E., Kaner, R., Chadburn, A., Zhao, Z., Steen, H., Pascual, V., Buenrostro, J., Niec, R., Lief, L., Ucar, D., Josefowicz, S.. 2022-02-10. Epigenetic Memory of COVID-19 in Innate Immune Cells and Their Progenitors. https://doi.org/10.1101/2022.02.09.479588

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