Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge

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.

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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. identifier: NCT04865237.

Item Type: Article
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: 18 Jan 2023 21:11
DOI: 10.21203/
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