Open Orphan has released the results from its Covid-19 characterisation study, which was a partnership between hVIVO, Imperial College London, the Vaccine Taskforce and Department of Health and Social Care (DHSC), and the Royal Free London NHS Foundation Trust. The results from this study show that a SARS-CoV-2 human challenge is safe in healthy young adults and provide insights into the course of Covid-19 infection with potential positive public health implications.
The study
As part of the characterisation study, researchers aimed to identify a dose of Covid-19 that caused a safe and reliable infection in unvaccinated volunteers with no prior SARS-CoV-2 infection. The results published today detail the outcome of the 36 healthy male and female volunteers aged 18-29 years which were infected with the original SARS-CoV-2 strain challenge virus. hVIVO clinicians closely monitored volunteers in a controlled quarantined setting and collected disease progression data to provide insights into Covid-19 infection. Volunteers will be followed up for 12 months after discharge from the quarantine facility.
Key clinical insights
Viral load (“VL”)
- 18 volunteers (50%) became infected with viral load (VL) rising steeply and peaking at ~five days post-inoculation
- No quantitative correlation was noted between VL and symptoms
Symptoms
- No serious symptoms
- Mild-to-moderate cold like symptoms were reported by 16 (88%) of 18 infected volunteers including a stuffy or runny nose, sneezing, and a sore throat. Some experienced headaches, muscle/joint aches, tiredness and fever
- Anosmia (lost or changed sense of smell) occurred in 13 (72% of infected) volunteers
Virus detection
- Average time from first exposure to viral detection and early symptoms (incubation period) was 42 hours
- Virus was detected earliest in the throat but at significantly greater levels in the nose;
- Virus detected in the throat on average after 40 hours
- Virus detected in the nose on average after 58 hours
- High levels of viable (infectious) virus was seen for approximately nine days post-inoculation, and up to a maximum of 12 days
- Modelling using the study data indicated that regular asymptomatic lateral flow testing (“LFT”) would diagnose infection before 70-80% of infectious virus had been generated, thus if isolation was triggered would decrease community transmission to others
Importantly, no serious adverse events (SAEs) occurred, and the SARS-CoV-2 human challenge study model was shown to be safe and well tolerated in healthy young adults.
With the characterisation study disease modelling data completed, and a Covid-19 Human Challenge Model now established, the company should be able to contract or conduct Covid-19 human challenge studies in 2022, subject to individual ethics and regulatory approvals. The company is already developing a Delta strain of the Covid-19 virus in partnership with Imperial College London and funded by the Wellcome Trust, which could be used in future trials.
Implications for public health
The characterisation study results and the insights they provide into Covid-19 infection have potential implications for public health. During the study, the average incubation period was 42 hours, which is considerably shorter than existing estimates of five to six days. Results also showed that while virus was detected significantly earlier in the throat, peak levels of virus were far higher in the nose, implying a potentially higher risk of viral shedding from the nose. This underlines the importance of proper facemask use to cover both the mouth and nose. Additionally, insights into the timeline of infection, with viable virus seen after nine days and 12 days for some, support the isolation periods advocated in most guidelines.
Lateral flow tests (LFTs) were also shown to be a good indicator of whether someone was harbouring viable virus. Positive LFTs correlated well with lab-confirmed detection of virus from swabs throughout the course of infection, including in those who were asymptomatic. However, the tests were less effective in picking up lower levels of virus at the very start and end of infection.
Official comments
Cathal Friel, Executive Chairman of Open Orphan, said: “I am delighted that the world’s first Covid-19 characterisation study has completed with no serious adverse events or serious symptoms, demonstrating that a Covid-19 human challenge study is safe in healthy young adults. The results, which have been made public today, have provided invaluable insights into Covid-19 disease progression.
“Crucially, we have now successfully established a Covid-19 Human Challenge Model which could be instrumental in accelerating the development of future Covid-19 therapeutics. New variants, such as Omicron, often mean that vaccines and antivirals have to be quickly re-evaluated to ensure effectiveness. Human challenge studies could prove to be the fastest way to compare old and new vaccines and therapies.”
Dr Andrew Catchpole, Co-investigator on the study and Chief Scientific Officer of hVIVO, said: “While the characterisation study was focused on the original SARS-CoV-2 strain, and there are differences in transmissibility between it and the other variants, the same factors will be responsible for protection against it, meaning the findings remain valuable for variants such as Delta or Omicron. These data provide a clear platform to now utilise the human challenge model to expedite product efficacy testing for new vaccines or antivirals”
