Multi-cohort analysis of host immune response identifies conserved protective and detrimental modules associated with severity across viruses.

Autor:	Zheng H; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA; Center for Biomedical Informatics Research, Department of Medicine, School of Medicine, Stanford University, CA 94305, USA., Rao AM; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA; Immunology program, Stanford University, CA 94305, USA., Dermadi D; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA; Center for Biomedical Informatics Research, Department of Medicine, School of Medicine, Stanford University, CA 94305, USA., Toh J; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA; Immunology program, Stanford University, CA 94305, USA., Murphy Jones L; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA; Center for Biomedical Informatics Research, Department of Medicine, School of Medicine, Stanford University, CA 94305, USA; Division of Critical Care Medicine, Department of Pediatrics, School of Medicine, Stanford University, CA 94305, USA., Donato M; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA; Center for Biomedical Informatics Research, Department of Medicine, School of Medicine, Stanford University, CA 94305, USA., Liu Y; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA; Cancer Biology program, Stanford University, CA 94305, USA., Su Y; Institute for Systems Biology, Seattle, WA, USA., Dai CL; Institute for Systems Biology, Seattle, WA, USA., Kornilov SA; Institute for Systems Biology, Seattle, WA, USA., Karagiannis M; 4(th) Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, 124 62 Athens, Greece., Marantos T; 4(th) Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, 124 62 Athens, Greece., Hasin-Brumshtein Y; Inflammatix, Inc. Burlingame, CA, USA., He YD; Inflammatix, Inc. Burlingame, CA, USA., Giamarellos-Bourboulis EJ; 4(th) Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, 124 62 Athens, Greece., Heath JR; Institute for Systems Biology, Seattle, WA, USA; Department of Bioengineering, University of Washington, Seattle, WA 98195., Khatri P; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, CA 94305, USA; Center for Biomedical Informatics Research, Department of Medicine, School of Medicine, Stanford University, CA 94305, USA. Electronic address: pkhatri@stanford.edu.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2021 Apr 13; Vol. 54 (4), pp. 753-768.e5. Date of Electronic Publication: 2021 Mar 24.
DOI:	10.1016/j.immuni.2021.03.002
Abstrakt:	Viral infections induce a conserved host response distinct from bacterial infections. We hypothesized that the conserved response is associated with disease severity and is distinct between patients with different outcomes. To test this, we integrated 4,780 blood transcriptome profiles from patients aged 0 to 90 years infected with one of 16 viruses, including SARS-CoV-2, Ebola, chikungunya, and influenza, across 34 cohorts from 18 countries, and single-cell RNA sequencing profiles of 702,970 immune cells from 289 samples across three cohorts. Severe viral infection was associated with increased hematopoiesis, myelopoiesis, and myeloid-derived suppressor cells. We identified protective and detrimental gene modules that defined distinct trajectories associated with mild versus severe outcomes. The interferon response was decoupled from the protective host response in patients with severe outcomes. These findings were consistent, irrespective of age and virus, and provide insights to accelerate the development of diagnostics and host-directed therapies to improve global pandemic preparedness. Competing Interests: Declaration of interests E.J.G.B. has received honoraria from Abbott CH, Angelini Italy, bioMérieux Inc, InflaRx GmbH, MSD Greece, and XBiotech Inc.; independent educational grants from AbbVie, Abbott, Astellas Pharma Europe, AxisShield, bioMérieux Inc, InflaRx GmbH, ThermoFisher Brahms GmbH, and XBiotech Inc; and funding from the FrameWork 7 program HemoSpec (granted to the National and Kapodistrian University of Athens), the Horizon2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), and the Horizon 2020 European Grant ImmunoSep (granted to the Hellenic Institute for the Study of Sepsis). P.K. is a shareholder and a consultant to Inflammatix, Inc. Y.H.B. and Y.D.H. are employees of, and stockholders in, Inflammatix, Inc. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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