TY - JOUR
TI - Multi-cohort analysis of host immune response identifies conserved protective and detrimental modules associated with severity across viruses
AU - Zheng, H.
AU - Rao, A.M.
AU - Dermadi, D.
AU - Toh, J.
AU - Murphy Jones, L.
AU - Donato, M.
AU - Liu, Y.
AU - Su, Y.
AU - Dai, C.L.
AU - Kornilov, S.A.
AU - Karagiannis, M.
AU - Marantos, T.
AU - Hasin-Brumshtein, Y.
AU - He, Y.D.
AU - Giamarellos-Bourboulis, E.J.
AU - Heath, J.R.
AU - Khatri, P.
JO - Invertebrate Immunity
PY - 2021
VL - 54
TODO - 4
SP - 753-768.e5
PB - Cell Press
SN - 2084-767X
TODO - 10.1016/j.immuni.2021.03.002
TODO - interferon;  transcriptome;  interferon;  transcriptome, adolescent;  aged;  antigen presentation;  Article;  blood sampling;  bone marrow cell;  cell differentiation;  chikungunya;  child;  cohort analysis;  controlled study;  deconvolution;  disease classification;  disease severity;  Ebola hemorrhagic fever;  female;  gene expression;  hematopoiesis;  hospital patient;  human;  immune response;  immunocompetent cell;  immunosuppressive treatment;  infant;  influenza;  major clinical study;  male;  monocyte;  myeloid dendritic cell;  myeloid-derived suppressor cell;  myelopoiesis;  newborn;  pandemic;  priority journal;  Severe acute respiratory syndrome coronavirus 2;  single cell RNA seq;  virus gene;  blood;  classification;  genetics;  immunity;  immunology;  natural killer cell;  pathogenicity;  pathology;  prognosis;  severity of illness index;  systems biology;  virus;  virus infection, Antigen Presentation;  Cohort Studies;  Hematopoiesis;  Humans;  Immunity;  Interferons;  Killer Cells, Natural;  Myeloid Cells;  Prognosis;  Severity of Illness Index;  Systems Biology;  Transcriptome;  Virus Diseases;  Viruses
TODO - 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. © 2021 The Author(s)
ER -