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Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19.
Feyaerts, Dorien; Hédou, Julien; Gillard, Joshua; Chen, Han; Tsai, Eileen S; Peterson, Laura S; Ando, Kazuo; Manohar, Monali; Do, Evan; Dhondalay, Gopal K R; Fitzpatrick, Jessica; Artandi, Maja; Chang, Iris; Snow, Theo T; Chinthrajah, R Sharon; Warren, Christopher M; Wittman, Richard; Meyerowitz, Justin G; Ganio, Edward A; Stelzer, Ina A; Han, Xiaoyuan; Verdonk, Franck; Gaudillière, Dyani K; Mukherjee, Nilanjan; Tsai, Amy S; Rumer, Kristen K; Jacobsen, Danielle R; Bjornson-Hooper, Zachary B; Jiang, Sizun; Saavedra, Sergio Fragoso; Valdés Ferrer, Sergio Iván; Kelly, J Daniel; Furman, David; Aghaeepour, Nima; Angst, Martin S; Boyd, Scott D; Pinsky, Benjamin A; Nolan, Garry P; Nadeau, Kari C; Gaudillière, Brice; McIlwain, David R.
  • Feyaerts D; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Hédou J; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Gillard J; Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands; Center for Molecular and Biomolecular Informatics,
  • Chen H; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
  • Tsai ES; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Peterson LS; Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
  • Ando K; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Manohar M; Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.
  • Do E; Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.
  • Dhondalay GKR; Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.
  • Fitzpatrick J; Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.
  • Artandi M; Department of Primary Care and Population Health, Stanford University School of Medicine, Stanford, CA, USA.
  • Chang I; Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.
  • Snow TT; Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.
  • 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; Division of Infectious Dis
  • Warren CM; Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.
  • Wittman R; Department of Primary Care and Population Health, Stanford University School of Medicine, Stanford, CA, USA.
  • Meyerowitz JG; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Ganio EA; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Stelzer IA; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • 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.
  • Verdonk F; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Gaudillière DK; Division of Plastic & Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Mukherjee N; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
  • Tsai AS; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Rumer KK; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Jacobsen DR; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Bjornson-Hooper ZB; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
  • Jiang S; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
  • Saavedra SF; Departamento de Neurología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Plan de Estudios Combinados en Medicina (MD/PhD Program), Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
  • Valdés Ferrer SI; Departamento de Neurología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
  • Kelly JD; Department of Epidemiology and Biostatistics, UCSF, San Francisco, CA, USA; Institute for Global Health Sciences, UCSF, San Francisco, CA, USA; F.I. Proctor Foundation, UCSF, San Francisco, CA, USA.
  • Furman D; Buck Artificial Intelligence Platform, 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), Un
  • Aghaeepour N; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA; Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA; Department of Biomedical Data Science, Stanf
  • Angst MS; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Boyd SD; Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • 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.
  • Nolan GP; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: gnolan@stanford.edu.
  • 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, Di
  • Gaudillière B; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA; Department of Pediatrics, Stanford University, Stanford, CA, USA. Electronic address: gbrice@stanford.edu.
  • McIlwain DR; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Cell Rep Med ; 3(7): 100680, 2022 07 19.
Article in English | MEDLINE | ID: covidwho-1907870
ABSTRACT
The biological determinants underlying the range of coronavirus 2019 (COVID-19) clinical manifestations are not fully understood. Here, over 1,400 plasma proteins and 2,600 single-cell immune features comprising cell phenotype, endogenous signaling activity, and signaling responses to inflammatory ligands are cross-sectionally assessed in peripheral blood from 97 patients with mild, moderate, and severe COVID-19 and 40 uninfected patients. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identify and independently validate a multi-variate model classifying COVID-19 severity (multi-class area under the curve [AUC]training = 0.799, p = 4.2e-6; multi-class AUCvalidation = 0.773, p = 7.7e-6). Examination of informative model features reveals biological signatures of COVID-19 severity, including the dysregulation of JAK/STAT, MAPK/mTOR, and nuclear factor κB (NF-κB) immune signaling networks in addition to recapitulating known hallmarks of COVID-19. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for prevention and/or treatment of COVID-19 progression.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Prognostic study / Randomized controlled trials Limits: Humans Language: English Journal: Cell Rep Med Year: 2022 Document Type: Article Affiliation country: J.xcrm.2022.100680

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Prognostic study / Randomized controlled trials Limits: Humans Language: English Journal: Cell Rep Med Year: 2022 Document Type: Article Affiliation country: J.xcrm.2022.100680