This research has not been peer-reviewed. It is a preliminary report that should not be regarded as conclusive, guide clinical practice or health-related behaviour, or be reported in news media as established information.
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 TCID50 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 log10 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.
Author list:
Affiliations:
- Department of Infectious Diseases, University College London Hospital, London, UK,
- hVIVO Services Ltd., London, UK,
- Department of Infectious Disease, Imperial College London, London, UK,
- UK Vaccine Taskforce, Department of Business, Energy and Industrial Strategy, London, UK,
- Department of Radiology, Royal Free London NHS Foundation Trust, London, UK,
- National Heart and Lung Institute, Imperial College London, London, UK,
- ENT Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK,
- Faculty of Medicine and Institute for Life Sciences, University of Southampton, and NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK,
- Department of Radiology, Southampton General Hospital, Southampton, UK,
- Department of Paediatrics, University of Oxford, Oxford, UK,
- S-cubed Biometrics, Abingdon, UK,
- Department of Infectious Diseases, Royal Free London NHS Foundation Trust, London, UK,
- Division of Epidemiology and Public Health, University of Nottingham School of Medicine, Nottingham, UK,
- 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,
- MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, UK,
- Imperial College London
Authors:
Ben Killingley1, Alex Mann2, Mariya Kalinova2, Alison Boyers2, Niluka Goonawardane3, Jie Zhou3, Kate Lindsell4, Samanjit S. Hare5, Jonathan Brown3, Rebecca Frise3, Emma Smith6, Claire Hopkins7, Nicolas Noulin2, Brandon Londt2, Tom Wilkinson8, Stephen Harden9, Helen McShane10, Mark Baillet11, Anthony Gilbert4, Michael Jacobs12, Christine Charman4, Priya Mande4, Jonathan S. Nguyen-Van-Tam13, Malcolm G. Semple14, Robert C. Read8, Neil M. Ferguson15, Peter J. Openshaw6, Garth Rapeport6, Wendy S. Barclay3, Andrew P. Catchpole2, Christopher Chiu16
