Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19
Abstract
Our understanding of protective versus pathological immune responses to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is limited by inadequate profiling of patients at the extremes of the disease severity spectrum. Here, we performed multi-omic single-cell immune profiling of 64 COVID-19 patients across the full range of disease severity, from outpatients with mild disease to fatal cases. Our transcriptomic, epigenomic, and proteomic analyses revealed widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19, including prominent hyperactivation signatures in neutrophils and NK cells. We also identified chromatin accessibility changes at NF-κB binding sites within cytokine gene loci as a potential mechanism for the striking lack of pro-inflammatory cytokine production observed in monocytes in severe and fatal COVID-19. We further demonstrated that emergency myelopoiesis is a prominent feature of fatal COVID-19. Collectively, our results reveal disease severity–associated immune phenotypes in COVID-19 and identify pathogenesis-associated pathways that are potential targets for therapeutic intervention.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 15, 2021
- Source ID
- 10.1084/jem.20210582
Entities
People
- Aaron J Wilk
- Andra L. Blomkalns
- Andrea Baird
- Andrea Fernandes
- Angela J Rogers
- Anita Visweswaran
- Arjun Rustagi
- Bei Wei
- Benjamin Parks
- Catherine Blish
- David Jimenez-Morales
- Donald Schreiber
- Drina Bogusch
- Elizabeth J. Zudock
- Euan A. Ashley
- Evan Do
- Geoff Ivison
- Georgie Nahass
- Giovanny J. Martinez-colon
- Giovanny Martínez-Colón
- Hena Din
- Iris Chang
- James Krempski
- James V. Quinn
- Jennifer A. Newberry
- Jonasel Roque
- Julia L. Mckechnie
- Kari C. Nadeau
- Kari Christine Nadeau
- Kathleen Whittle Dantzler
- Kathryn Jee
- Kazim Haider
- Kim Quyen Thi Tran
- Komal Kumar
- Laura Simpson
- Lauren De La Parte
- Madeline Lee
- Marlene Rabinovitch
- Maureen Ty
- Michal Tal
- Michele Ugur
- Monali Manohar
- Nancy Q Zhao
- Nimish Kathale
- Rachel Brewer
- Rosemary Vergara
- Rosen Mann
- Ruoxi Pi
- Ruth O'Hara
- Samuel Yang
- Shalina Taylor
- Shu-chen Lyu
- Stanford Covid-19 Biobank
- Susan P. Holmes
- Taylor Hollis
- Thanmayi Ranganath
- Wenming Zhang
- William Greenleaf
- Winston R. Becker
Organizations
- Burroughs Wellcome Fund
- Chan Zuckerberg Biohub
- Chan Zuckerberg Initiative
- Defense Advanced Research Projects Agency
- Emerson Collective
- Gates Foundation
- National Heart, Lung, and Blood Institute
- National Institute of Standards and Technology
- National Institute on Drug Abuse
- National Institutes of Health
- Rita Allen Foundation
- Stanford University