Killingley, Ben, Mann, Alex, Kalinova, Mariya 
ORCID: 0000-0002-3744-4604, Boyers, Alison, Goonawardane, Niluka ORCID: 0000-0003-2906-5513, Zhou, Jie, Lindsell, Kate, Hare, Samanjit, Brown, Jonathan ORCID: 0000-0001-6849-3962, Frise, Rebecca et al (show 21 more authors)
(2022)
Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge.
ResearchSquare.
Abstract
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 50 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 10 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Lung, Infectious Diseases, Emerging Infectious Diseases, Prevention, Biodefense, Vaccine Related, Clinical Research, Infection |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 28 Feb 2022 08:06 |
| Last Modified: | 11 Apr 2024 19:24 |
| DOI: | 10.21203/rs.3.rs-1121993/v1 |
| Open Access URL: | http://doi.org/10.21203/rs.3.rs-1121993/v1 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3149803 |
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