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Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19.
Su, Yapeng; Chen, Daniel; Yuan, Dan; Lausted, Christopher; Choi, Jongchan; Dai, Chengzhen L; Voillet, Valentin; Duvvuri, Venkata R; Scherler, Kelsey; Troisch, Pamela; Baloni, Priyanka; Qin, Guangrong; Smith, Brett; Kornilov, Sergey A; Rostomily, Clifford; Xu, Alex; Li, Jing; Dong, Shen; Rothchild, Alissa; Zhou, Jing; Murray, Kim; Edmark, Rick; Hong, Sunga; Heath, John E; Earls, John; Zhang, Rongyu; Xie, Jingyi; Li, Sarah; Roper, Ryan; Jones, Lesley; Zhou, Yong; Rowen, Lee; Liu, Rachel; Mackay, Sean; O'Mahony, D Shane; Dale, Christopher R; Wallick, Julie A; Algren, Heather A; Zager, Michael A; Wei, Wei; Price, Nathan D; Huang, Sui; Subramanian, Naeha; Wang, Kai; Magis, Andrew T; Hadlock, Jenn J; Hood, Leroy; Aderem, Alan; Bluestone, Jeffrey A; Lanier, Lewis L.
  • Su Y; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Chen D; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Yuan D; Institute for Systems Biology, Seattle, WA 98109, USA; Department of Bioengineering, University of Washington, Seattle, WA 98105, USA.
  • Lausted C; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Choi J; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Dai CL; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Voillet V; Cape Town HVTN Immunology Laboratory, Hutchinson Centre Research Institute of South Africa, NPC (HCRISA), Cape Town 8001, South Africa; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Duvvuri VR; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Scherler K; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Troisch P; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Baloni P; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Qin G; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Smith B; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Kornilov SA; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Rostomily C; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Xu A; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Li J; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Dong S; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Rothchild A; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA.
  • Zhou J; Isoplexis Corporation, Branford, CT 06405, USA.
  • Murray K; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Edmark R; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Hong S; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Heath JE; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Earls J; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Zhang R; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Xie J; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Li S; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Roper R; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Jones L; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Zhou Y; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Rowen L; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Liu R; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Mackay S; Isoplexis Corporation, Branford, CT 06405, USA.
  • O'Mahony DS; Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA 98109, USA; Providence St. Joseph Health, Renton, WA 98057, USA.
  • Dale CR; Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA 98109, USA; Providence St. Joseph Health, Renton, WA 98057, USA.
  • Wallick JA; Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA 98109, USA; Providence St. Joseph Health, Renton, WA 98057, USA.
  • Algren HA; Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA 98109, USA; Providence St. Joseph Health, Renton, WA 98057, USA.
  • Zager MA; Center for Data Visualization, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Wei W; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Price ND; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Huang S; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Subramanian N; Institute for Systems Biology, Seattle, WA 98109, USA; Department of Global Heath, and Department of Immunology, University of Washington, Seattle, WA 98109, USA.
  • Wang K; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Magis AT; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Hadlock JJ; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Hood L; Institute for Systems Biology, Seattle, WA 98109, USA; Providence St. Joseph Health, Renton, WA 98057, USA.
  • Aderem A; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA.
  • Bluestone JA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Lanier LL; Department of Microbiology and Immunology, University of California, San Francisco, and Parker Institute for Cancer Immunotherapy, San Francisco, CA 94143, USA.
Cell ; 183(6): 1479-1495.e20, 2020 12 10.
Article in English | MEDLINE | ID: covidwho-917236
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Genomics / Single-Cell Analysis / RNA-Seq / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Cell Year: 2020 Document Type: Article Affiliation country: J.cell.2020.10.037

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Genomics / Single-Cell Analysis / RNA-Seq / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Cell Year: 2020 Document Type: Article Affiliation country: J.cell.2020.10.037