Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge
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- Ben Killingley
- Department of Infectious Diseases, University College London Hospital, London, UK
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- Alex Mann
- hVIVO Services Ltd., London, UK
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- Mariya Kalinova
- hVIVO Services Ltd., London, UK
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- Alison Boyers
- hVIVO Services Ltd., London, UK
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- Niluka Goonawardane
- Department of Infectious Disease, Imperial College London, London, UK
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- Jie Zhou
- Department of Infectious Disease, Imperial College London, London, UK
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- Kate Lindsell
- UK Vaccine Taskforce, Department of Business, Energy and Industrial Strategy, London, UK
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- Samanjit S. Hare
- Department of Radiology, Royal Free London NHS Foundation Trust, London, UK
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- Jonathan Brown
- Department of Infectious Disease, Imperial College London, London, UK
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- Rebecca Frise
- Department of Infectious Disease, Imperial College London, London, UK
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- Emma Smith
- National Heart and Lung Institute, Imperial College London, London, UK
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- Claire Hopkins
- ENT Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK
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- Nicolas Noulin
- hVIVO Services Ltd., London, UK
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- Brandon Londt
- hVIVO Services Ltd., London, UK
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- Tom Wilkinson
- Faculty of Medicine and Institute for Life Sciences, University of Southampton, and NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK
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- Stephen Harden
- Department of Radiology, Southampton General Hospital, Southampton, UK
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- Helen McShane
- Department of Paediatrics, University of Oxford, Oxford, UK
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- Mark Baillet
- S-cubed Biometrics, Abingdon, UK
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- Anthony Gilbert
- UK Vaccine Taskforce, Department of Business, Energy and Industrial Strategy, London, UK
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- Michael Jacobs
- Department of Infectious Diseases, Royal Free London NHS Foundation Trust, London, UK
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- Christine Charman
- UK Vaccine Taskforce, Department of Business, Energy and Industrial Strategy, London, UK
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- Priya Mande
- UK Vaccine Taskforce, Department of Business, Energy and Industrial Strategy, London, UK
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- Jonathan S. Nguyen-Van-Tam
- Division of Epidemiology and Public Health, University of Nottingham School of Medicine, Nottingham, UK
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- Malcolm G. Semple
- Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool; Respiratory Department, Alder Hey Children’s Hospital, Liverpool, UK
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- Robert C. Read
- Faculty of Medicine and Institute for Life Sciences, University of Southampton, and NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK
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- Neil M. Ferguson
- MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, UK
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- Peter J. Openshaw
- National Heart and Lung Institute, Imperial College London, London, UK
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- Garth Rapeport
- National Heart and Lung Institute, Imperial College London, London, UK
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- Wendy S. Barclay
- Department of Infectious Disease, Imperial College London, London, UK
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- Andrew P. Catchpole
- hVIVO Services Ltd., London, UK
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- Christopher Chiu
- Imperial College London
抄録
<jats:title>Abstract</jats:title> <jats:p>To establish a novel SARS-CoV-2 human challenge model, 36 volunteers aged 18-29 years without evidence of previous infection or vaccination were inoculated with 10 TCID<jats:sub>50</jats:sub> of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally. Two participants were excluded from per protocol analysis due to seroconversion between screening and inoculation. Eighteen (~53%) became infected, with viral load (VL) rising steeply and peaking at ~5 days post-inoculation. Virus was first detected in the throat but rose to significantly higher levels in the nose, peaking at ~8.87 log<jats:sub>10</jats:sub> copies/ml (median, 95% CI [8.41,9.53). Viable virus was recoverable from the nose up to ~10 days post-inoculation, on average. There were no serious adverse events. Mild-to-moderate symptoms were reported by 16 (89%) infected individuals, beginning 2-4 days post-inoculation. Anosmia/dysosmia developed more gradually in 12 (67%) participants. No quantitative correlation was noted between VL and symptoms, with high VLs even in asymptomatic infection, followed by the development of serum spike-specific and neutralising antibodies. However, lateral flow results were strongly associated with viable virus and modelling showed that twice-weekly rapid tests could diagnose infection before 70-80% of viable virus had been generated. Thus, in this first SARS-CoV-2 human challenge study, no serious safety signals were detected and the detailed characteristics of early infection and their public health implications were shown. ClinicalTrials.gov identifier: NCT04865237.</jats:p>
収録刊行物
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- Nat. Med.
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Nat. Med. 28 1031-, 2022-02-01
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