Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19.

Journal

bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
10 Feb 2021
Historique:
entrez: 17 2 2021
pubmed: 18 2 2021
medline: 18 2 2021
Statut: epublish

Résumé

The biological determinants of the wide spectrum of COVID-19 clinical manifestations are not fully understood. Here, over 1400 plasma proteins and 2600 single-cell immune features comprising cell phenotype, basal signaling activity, and signaling responses to inflammatory ligands were assessed in peripheral blood from patients with mild, moderate, and severe COVID-19, at the time of diagnosis. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identified and independently validated a multivariate model classifying COVID-19 severity (multi-class AUCtraining = 0.799, p-value = 4.2e-6; multi-class AUCvalidation = 0.773, p-value = 7.7e-6). Features of this high-dimensional model recapitulated recent COVID-19 related observations of immune perturbations, and revealed novel biological signatures of severity, including the mobilization of elements of the renin-angiotensin system and primary hemostasis, as well as dysregulation of JAK/STAT, MAPK/mTOR, and NF-κB immune signaling networks. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for the prevention of COVID-19 progression.

Identifiants

DOI: 10.1101/2021.02.09.430269 PMID: 33594362 PMC: PMC7885914
pubmed: 33594362
doi: 10.1101/2021.02.09.430269
pmc: PMC7885914
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NIGMS NIH HHS
ID : R35 GM137936
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM130900
Pays : United States
Organisme : NIAID NIH HHS
ID : K23 AI146268
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM138353
Pays : United States
Organisme : Doris Duke Charitable Foundation
ID : 2018100
Pays : United States

Commentaires et corrections

Type : UpdateIn

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Auteurs

Dorien Feyaerts (D)

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Julien Hédou (J)

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Joshua Gillard (J)

Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.
Radboud Center for Infectious Diseases, Radboudumc, Nijmegen, the Netherlands.

Han Chen (H)

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.

Eileen S Tsai (ES)

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Laura S Peterson (LS)

Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.

Kazuo Ando (K)

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Monali Manohar (M)

Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.

Evan Do (E)

Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.

Gopal K R Dhondalay (GKR)

Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.

Jessica Fitzpatrick (J)

Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.

Maja Artandi (M)

Department of Primary Care and Population Health, Stanford University School of Medicine, Stanford, CA, USA.

Iris Chang (I)

Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.

Theo T Snow (TT)

Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.

R Sharon Chinthrajah (RS)

Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.
Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Stanford University, Stanford, CA, USA.
Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA, USA.

Christopher M Warren (CM)

Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.

Rich Wittman (R)

Department of Primary Care and Population Health, Stanford University School of Medicine, Stanford, CA, USA.

Justin G Meyerowitz (JG)

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Edward A Ganio (EA)

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Ina A Stelzer (IA)

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Xiaoyuan Han (X)

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Department of Biomedical Sciences, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, CA, USA.

Franck Verdonk (F)

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Dyani K Gaudillière (DK)

Division of Plastic & Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.

Nilanjan Mukherjee (N)

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.

Amy S Tsai (AS)

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Kristen K Rumer (KK)

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Sizun Jiang (S)

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.

Sergio Iván Valdés Ferrer (SI)

Departamento de Neurología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

J Daniel Kelly (JD)

Department of Epidemiology and Biostatistics, UCSF, San Francisco, CA, USA.
Institute of Global Health Sciences, UCSF, San Francisco, CA, USA.
F.I. Proctor Foundation, UCSF, San Francisco, CA, USA.

David Furman (D)

Buck Artificial Intelligence Platform, the Buck Institute for Research on Aging, Novato, CA, USA.
Stanford 1000 Immunomes Project, Stanford University School of Medicine, Stanford, CA, USA.
Austral Institute for Applied Artificial Intelligence, Institute for Research in Translational Medicine (IIMT), Universidad Austral, CONICET, Pilar, Buenos Aires, Argentina.

Nima Aghaeepour (N)

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Department of Biomedical Informatics, Stanford University School of Medicine, Stanford, CA, USA.

Martin S Angst (MS)

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Scott D Boyd (SD)

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.

Benjamin A Pinsky (BA)

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Garry P Nolan (GP)

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.

Kari C Nadeau (KC)

Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.
Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Stanford University, Stanford, CA, USA.
Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA, USA.

Brice Gaudillière (B)

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

David R McIlwain (DR)

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.

Classifications MeSH