TY - JOUR T1 - Epigenetic Memory of COVID-19 in Innate Immune Cells and Their Progenitors JF - bioRxiv DO - 10.1101/2022.02.09.479588 SP - 2022.02.09.479588 AU - Jin-Gyu Cheong AU - Arjun Ravishankar AU - Siddhartha Sharma AU - Christopher N. Parkhurst AU - Djamel Nehar-Belaid AU - Sai Ma AU - Lucinda Paddock AU - Benoit Fatou AU - Onur Karakaslar AU - Asa Thibodeau AU - Michael J. Bale AU - Vinay K. Kartha AU - Jim K Yee AU - Minh Yen Mays AU - Louise Leyre AU - Alexia Martinez de Paz AU - Andrew W. Daman AU - Sergio Alvarez Mullett AU - Lexi Robbins AU - Elyse LaFond AU - Karissa Weidman AU - Sabrina Racine-Brzostek AU - He S. Yang AU - David Price AU - Brad Jones AU - Edward J. Schenck AU - Robert J. Kaner AU - Amy Chadburn AU - Zhen Zhao AU - Hanno Steen AU - Virginia Pascual AU - Jason Buenrostro AU - Rachel E. Niec AU - Lindsay Lief AU - Duygu Ucar AU - Steven Z. Josefowicz Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/02/10/2022.02.09.479588.abstract N2 - 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 Summary Transcriptomic and epigenomic analysis of blood reveal sustained changes in hematopoiesis and innate immunity after COVID-19.Competing Interest StatementJ.D.B. holds patents related to ATAC-seq and scATAC-seq and serves on the Scientific Advisory Board of CAMP4 Therapeutics, seqWell, and CelSee. ER -