Epigenetic memory of coronavirus infection in innate immune cells and their progenitors.

TitleEpigenetic memory of coronavirus infection in innate immune cells and their progenitors.
Publication TypeJournal Article
Year of Publication2023
AuthorsCheong J-G, Ravishankar A, Sharma S, Parkhurst CN, Grassmann SA, Wingert CK, Laurent P, Ma S, Paddock L, Miranda IC, Karakaslar EOnur, Nehar-Belaid D, Thibodeau A, Bale MJ, Kartha VK, Yee JK, Mays MY, Jiang C, Daman AW, de Paz AMartinez, Ahimovic D, Ramos V, Lercher A, Nielsen E, Alvarez-Mulett S, Zheng L, Earl A, Yallowitz A, Robbins L, LaFond E, Weidman KL, Racine-Brzostek S, Yang HS, Price DR, Leyre L, Rendeiro AF, Ravichandran H, Kim J, Borczuk AC, Rice CM, R Jones B, Schenck EJ, Kaner RJ, Chadburn A, Zhao Z, Pascual V, Elemento O, Schwartz RE, Buenrostro JD, Niec RE, Barrat FJ, Lief L, Sun JC, Ucar D, Josefowicz SZ
Date Published2023 Aug 31
KeywordsAnimals, Cell Differentiation, COVID-19, Disease Models, Animal, Epigenetic Memory, Hematopoietic Stem Cells, Humans, Inflammation, Mice, Monocytes, Post-Acute COVID-19 Syndrome, Trained Immunity

Inflammation can trigger lasting phenotypes in immune and non-immune cells. Whether and how human infections and associated inflammation can form innate immune memory in hematopoietic stem and progenitor cells (HSPC) has remained unclear. We found that circulating HSPC, enriched from peripheral blood, captured the diversity of bone marrow HSPC, enabling investigation of their epigenomic reprogramming following coronavirus disease 2019 (COVID-19). Alterations in innate immune phenotypes and epigenetic programs of HSPC persisted for months to 1 year following severe COVID-19 and were associated with distinct transcription factor (TF) activities, altered regulation of inflammatory programs, and durable increases in myelopoiesis. HSPC epigenomic alterations were conveyed, through differentiation, to progeny innate immune cells. Early activity of IL-6 contributed to these persistent phenotypes in human COVID-19 and a mouse coronavirus infection model. Epigenetic reprogramming of HSPC may underlie altered immune function following infection and be broadly relevant, especially for millions of COVID-19 survivors.

Custom 1


Alternate JournalCell
PubMed ID37597510
Grant ListR01 AI142086 / AI / NIAID NIH HHS / United States
U19 AI144301 / AI / NIAID NIH HHS / United States
RM1 GM139738 / GM / NIGMS NIH HHS / United States
R25 CA233208 / CA / NCI NIH HHS / United States
R01 AI148416 / AI / NIAID NIH HHS / United States
U01 AI165452 / AI / NIAID NIH HHS / United States
R01 AI132447 / AI / NIAID NIH HHS / United States
R01 AI161444 / AI / NIAID NIH HHS / United States

Weill Cornell Medicine Gale and Ira Drukier Institute for Children's Health 413 E. 69th Street New York, NY 10021