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      Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae

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      1 , 2 , 3 , 28 , , 1 , 4 , 28 , 1 , 5 , 28 , 1 , 4 , 1 , 1 , 1 , 1 , 1 , 4 , 1 , 6 , 1 , 1 , 7 , 8 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 3 , 9 , 7 , 10 , 11 , 12 , 1 , 1 , 13 , 13 , 14 , 14 , 14 , 14 , 14 , 14 , 1 , 1 , 15 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 16 , 17 , 16 , 17 , 16 , 17 , 16 , 17 , 16 , 17 , the ISB-Swedish COVID19 Biobanking Unit, Terri Wrin 18 , 18 , 19 , 19 , 1 , 19 , 1 , 1 , 20 , 2 , 12 , 1 , 1 , 21 , 22 , 10 , 8 , 11 , 12 , 1 , 17 , 2 , 23 , 24 , 25 , 3 , 9 , 7 , 26 , 27 , 2 , 12 , 16 , 17 , , 1 , 4 , 29 ,
      Cell
      The Author(s). Published by Elsevier Inc.

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          Abstract

          Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8 + T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.

          Abstract

          By correlating patient symptoms with in-depth profiling of blood cells and plasma components throughout COVID-19 infection, this study identifies factors that may predict sustained disease.

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          Author and article information

          Journal
          Cell
          Cell
          Cell
          The Author(s). Published by Elsevier Inc.
          0092-8674
          1097-4172
          25 January 2022
          25 January 2022
          Affiliations
          [1 ]Institute for Systems Biology, Seattle, WA, 98109, USA
          [2 ]Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA
          [3 ]Clinical Research Division, Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA
          [4 ]Department of Bioengineering, University of Washington, Seattle, WA, 98105, USA
          [5 ]Department of Microbiology and Department of Informatics, University of Washington, Seattle, WA, 98195, USA
          [6 ]Molecular Engineering & Sciences Institute, University of Washington, Seattle, WA, 98105, USA
          [7 ]Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, 94305, USA
          [8 ]Diabetes Center, University of California, San Francisco, CA, 94143, USA
          [9 ]Departments of Immunology and Medicine, University of Washington, Seattle, WA, 98109, USA
          [10 ]Department of Pathology, Stanford University, Stanford, CA, 94304, USA
          [11 ]Division of Global Health, University of Washington, Seattle, WA, 98105, USA
          [12 ]Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, 98109, USA
          [13 ]Isoplexis Corporation, Branford, CT, 06405, USA
          [14 ]Adaptive Biotechnologies, Seattle, WA, 98109, USA
          [15 ]Medical University of Białystok, Białystok, 15089, Poland
          [16 ]Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA, 98109, USA;
          [17 ]Providence St. Joseph Health, Renton, WA, 98057, USA
          [18 ]Monogram Biosciences, South San Francisco, CA, 94080, USA
          [19 ]St. John’s Cancer Institute at Saint John’s Health Center, Santa Monica, CA, 90404, USA
          [20 ]Department of Global Heath, and Department of Immunology, University of Washington, Seattle, WA, 98109, USA
          [21 ]Department of Medicine, University of California, Los Angeles, and Parker Institute for Cancer Immunotherapy, Los Angeles, CA, 90095, USA;
          [22 ]Department of Microbiology and Immunology, University of California, San Francisco, and Parker Institute for Cancer Immunotherapy, San Francisco, CA, 94143, USA
          [23 ]Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA
          [24 ]Department of Statistics, University of Washington, Seattle, WA, 98195, USA;
          [25 ]Biomedical Data Sciences, Lausanne University Hospital and University of Lausanne, Lausanne, 1011, Switzerland
          [26 ]Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, 94305, USA
          [27 ]The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA
          Author notes
          []Corresponding author (Y.S.), (J.D.G.), (J.R.H.),
          [28]

          These authors contributed equally

          [29]

          Lead contact

          Article
          S0092-8674(22)00072-1
          10.1016/j.cell.2022.01.014
          8786632
          35216672
          ab4c3ff1-8d93-40cc-8a4e-204fb234a0ce
          © 2022 The Author(s)

          Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

          History
          : 29 September 2021
          : 14 December 2021
          : 19 January 2022
          Categories
          Article

          Cell biology
          Cell biology

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