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

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 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.

Biomarker identification using dynamic time warping analysis: a longitudinal cohort study of patients with COVID-19 in a UK tertiary hospital

“…Future work would involve investigation of the role of viral load in the context of these findings in order to better understand the pathological mechanisms that are key in driving a more severe disease phenotype and with serial cytokine sampling of airways and blood to investigate the role of hyperinflammation in this. A mechanistic modelling of the pathobiology of SARS-CoV-2 infection would allow greater understanding of the pathological processes driving these prognostic responses and may also facilitate more targeted novel treatment trials for this disease43 44–49. Importantly, we have demonstrated the utility of a new approach, based on dynamic time warping analysis, for rapidly characterising emerging COVID-19 clinical cohorts and their trajectories.…”

A population framework for predicting the proportion of people infected by the far-field airborne transmission of SARS-CoV-2 indoors

“…As COVID-19 progresses the viral load reduces, normally within the first week after the onset of symptoms [41, 42]. The viral load also varies between people at any stage of the infection, which increases uncertainty in it [43, 44, 45, 19, 46, 18, 30, 37, 47].…”

Differentiating between infectious and non-infectious influenza A virus and coronavirus RNA levels using long-range RT-qPCR

“…Next, we compared the two-step, long-range RT-qPCR protocol to the one-step Taq-Path protocol on samples obtained at least 15 days after the onset of symptoms when the above patients had recovered. Based on recent human experimental model data, these patients are typically free of infectious virus (6). In line with our in vitro data (Fig.…”