Abstract

Rationale: To establish a novel SARS-CoV-2 human challenge model enabling controlled investigation of pathogenesis, correlates of protection and efficacy testing of interventions.

Methods: Thirty-six healthy 18-29-year-old subjects, without evidence of previous infection or vaccination, received 10 TCID50 of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally. Following inoculation, subjects resided in a high-containment quarantine, with 24-hour medical monitoring. The study’s main objectives were to identify a virus dose that induced well-tolerated infection in >50% of subjects and assess virus and symptoms over time. AEs and longitudinal disease profiles are presented.

Results: Eighteen of thirty-four evaluable (~53%) subjects became infected and developed serum antibodies. Viral load rose steeply and peaked ~5 days post-inoculation (PI). 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 PI, on average. Mild-to-moderate symptoms were reported by 16 (89%) infected subjects, beginning 2-4 days PI. Anosmia or dysosmia developed in 15 (83%) subjects. Results from lateral flow tests were associated with viable virus and modelling showed that twice-weekly rapid antigen tests could diagnose infection before 70-80% of viable virus had been generated. There were no overt lung function changes, CT abnormalities, or SAEs.

Conclusions: This novel SARS-CoV-2 challenge of 18-29-year-olds was considered safe. Viral kinetics over the course of primary infection was established, with implications for public health recommendations and strategies to impact transmission.