Severe Acute Respiratory Syndrome Coronavirus 2 Viremia Is Associated With Coronavirus Disease 2019 Severity and Predicts Clinical Outcomes

DOI PDF PDF 被引用文献3件
  • Jana L Jacobs
    Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  • William Bain
    Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  • Asma Naqvi
    Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  • Brittany Staines
    Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  • Priscila M S Castanha
    Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA
  • Haopu Yang
    Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  • Valerie F Boltz
    HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, USA
  • Simon Barratt-Boyes
    Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA
  • Ernesto T A Marques
    Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA
  • Stephanie L Mitchell
    Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  • Barbara Methé
    Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  • Tolani F Olonisakin
    Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  • Ghady Haidar
    Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  • Thomas W Burke
    Center for Applied Genomics and Precision Medicine, Duke University, Durham, North Carolina, USA
  • Elizabeth Petzold
    Center for Applied Genomics and Precision Medicine, Duke University, Durham, North Carolina, USA
  • Thomas Denny
    Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA
  • Chris W Woods
    Center for Applied Genomics and Precision Medicine, Duke University, Durham, North Carolina, USA
  • Bryan J McVerry
    Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  • Janet S Lee
    Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  • Simon C Watkins
    Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  • Claudette M St Croix
    Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  • Alison Morris
    Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  • Mary F Kearney
    HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, USA
  • Mark S Ladinsky
    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
  • Pamela J Bjorkman
    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
  • Georgios D Kitsios
    Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  • John W Mellors
    Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

説明

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA (vRNA) is detected in the bloodstream of some patients with coronavirus disease 2019 (COVID-19), but it is not clear whether this RNAemia reflects viremia (ie, virus particles) and how it relates to host immune responses and outcomes.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>SARS-CoV-2 vRNA was quantified in plasma samples from observational cohorts of 51 COVID-19 patients including 9 outpatients, 19 hospitalized (non–intensive care unit [ICU]), and 23 ICU patients. vRNA levels were compared with cross-sectional indices of COVID-19 severity and prospective clinical outcomes. We used multiple imaging methods to visualize virions in plasma.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>SARS-CoV-2 vRNA was detected in plasma of 100%, 52.6%, and 11.1% of ICU, non-ICU, and outpatients, respectively. Virions were detected in plasma pellets using electron tomography and immunostaining. Plasma vRNA levels were significantly higher in ICU &gt; non-ICU &gt; outpatients (P &lt; .0001); for inpatients, plasma vRNA levels were strongly associated with higher World Health Organization (WHO) score at admission (P = .01), maximum WHO score (P = .002), and discharge disposition (P = .004). A plasma vRNA level &gt;6000 copies/mL was strongly associated with mortality (hazard ratio, 10.7). Levels of vRNA were significantly associated with several inflammatory biomarkers (P &lt; .01) but not with plasma neutralizing antibody titers (P = .8).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Visualization of virus particles in plasma indicates that SARS-CoV-2 RNAemia is due, at least in part, to viremia. The levels of SARS-CoV-2 RNAemia correlate strongly with disease severity, patient outcome, and specific inflammatory biomarkers but not with neutralizing antibody titers.</jats:p> </jats:sec>

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