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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, Rich; Meyerowitz, Justin G; Ganio, Edward A; Stelzer, Ina A; Han, Xiaoyuan; Verdonk, Franck; Gaudillière, Dyani K; Mukherjee, Nilanjan; Tsai, Amy S; Rumer, Kristen K; Jiang, Sizun; 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.
Afiliación
  • 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.
  • Chen H; Radboud Center for Infectious Diseases, Radboudumc, Nijmegen, the Netherlands.
  • Tsai ES; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Peterson LS; Department of Microbiology and Immunology, 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; Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
  • Do E; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 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; Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, 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; Department of Primary Care and Population Health, Stanford University School of Medicine, 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.
  • 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; Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.
  • Meyerowitz JG; Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Stanford University, Stanford, CA, USA.
  • Ganio EA; Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA, USA.
  • Stelzer IA; Sean N Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA.
  • Han X; Department of Primary Care and Population Health, Stanford University School of Medicine, Stanford, CA, USA.
  • Verdonk F; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Gaudillière DK; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Mukherjee N; Department of Anesthesiology, Perioperative and Pain Medicine, 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 Biomedical Sciences, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, CA, USA.
  • Jiang S; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Valdés Ferrer SI; Division of Plastic & Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Kelly JD; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Furman D; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
  • Aghaeepour N; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Angst MS; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Boyd SD; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Pinsky BA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
  • Nolan GP; Departamento de Neurología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
  • Nadeau KC; Department of Epidemiology and Biostatistics, UCSF, San Francisco, CA, USA.
  • Gaudillière B; Institute of Global Health Sciences, UCSF, San Francisco, CA, USA.
  • McIlwain DR; F.I. Proctor Foundation, UCSF, San Francisco, CA, USA.
bioRxiv ; 2021 Feb 10.
Article en En | MEDLINE | ID: mdl-33594362
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos