Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19.
CITE-seq
COVID-19
immune response
infection
metabolomics
multi-omics
proteomics
single-cell RNA-seq
single-cell TCR-seq
single-cell secretome
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
10 12 2020
10 12 2020
Historique:
received:
13
07
2020
revised:
16
09
2020
accepted:
22
10
2020
pubmed:
11
11
2020
medline:
22
12
2020
entrez:
10
11
2020
Statut:
ppublish
Résumé
We present an integrated analysis of the clinical measurements, immune cells, and plasma multi-omics of 139 COVID-19 patients representing all levels of disease severity, from serial blood draws collected during the first week of infection following diagnosis. We identify a major shift between mild and moderate disease, at which point elevated inflammatory signaling is accompanied by the loss of specific classes of metabolites and metabolic processes. Within this stressed plasma environment at moderate disease, multiple unusual immune cell phenotypes emerge and amplify with increasing disease severity. We condensed over 120,000 immune features into a single axis to capture how different immune cell classes coordinate in response to SARS-CoV-2. This immune-response axis independently aligns with the major plasma composition changes, with clinical metrics of blood clotting, and with the sharp transition between mild and moderate disease. This study suggests that moderate disease may provide the most effective setting for therapeutic intervention.
Identifiants
pubmed: 33171100
pii: S0092-8674(20)31444-6
doi: 10.1016/j.cell.2020.10.037
pmc: PMC7598382
pii:
doi:
Types de publication
Clinical Trial
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1479-1495.e20Subventions
Organisme : NIAID NIH HHS
ID : R21 AI138258
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI057229
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA040395
Pays : United States
Organisme : NCATS NIH HHS
ID : UG3 TR002884
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI068129
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI128914
Pays : United States
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of Interests J.R.H. is founder and board member of Isoplexis and PACT Pharma. M.M.D. is a member of the Scientific Advisory Board of PACT Pharma. J.A.B. is a member of the Scientific Advisory Boards of Arcus, Celsius, and VIR. J.A.B. is a member of the Board of Directors of Rheos and Provention. J.A.B. has recently joined Sonoma Biotherapeutics as President and CEO. Sonoma Biotherapeutics is involved in developing novel Treg-based cell therapies for the treatment of autoimmune diseases. R.G. has received consulting income from Juno Therapeutics, Takeda, Infotech Soft, Celgene, Merck and has received research support from Janssen Pharmaceuticals and Juno Therapeutics, and declares ownership in CellSpace Biosciences. P.D.G is on the Scientific Advisory Board of Celsius, Earli, Elpiscience, Immunoscape, Rapt, and Nextech, was a scientific founder of Juno Therapeutics, and receives research support from Lonza. J.D.G. declared contracted research with Gilead, Lilly, and Regeneron. The remaining authors declare no competing interests.
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