Findings from the UK’s world-leading human challenge study suggest that Covid-19 symptoms start to develop very fast, on average about two days after contact with the virus compared to the previous estimate of around five to six days by the World Health Organisation (WHO).
The infection first appears in the throat; infectious virus peaks about five days into infection and, at that stage, is significantly more abundant in the nose than the throat, the study points out.
The study also found that lateral flow tests (LFTs) are a reassuringly reliable indicator of whether the infectious virus is present (i.e., whether they are likely to be able to transmit the virus to other people).
The collaborative study is the first in the world to perform detailed monitoring over the full course of Covid-19, from the moment a person first encounters SARS-CoV-2, throughout the infection to the point at which the virus is apparently eliminated.
The Human Challenge Programme is a partnership between Imperial College London, the Vaccine Taskforce and Department of Health and Social Care (DHSC), hVIVO (part of Open Orphan plc.), and the Royal Free London NHS Foundation Trust.
The findings, published on a pre-print server and which have not yet been peer-reviewed, detail the outcomes in 36 healthy, young participants with no immunity to the virus. This study took place at a specialist unit at the Royal Free Hospital in London, showing that experimental infection of volunteers is reproducible and resulted in no severe symptoms in healthy young adult participants, laying the groundwork for future studies to test new vaccines and medicines against Covid-19.
Professor Christopher Chiu, from the Department of Infectious Disease and the Institute of Infection at Imperial College London and Chief Investigator on the trial, said: “First and foremost, there were no severe symptoms or clinical concerns in our challenge infection model of healthy young adult participants.
"People in this age group are believed to be major drivers of the pandemic and these studies, which are representative of mild infection, allow detailed investigation of the factors responsible for infection and pandemic spread."
“Our study reveals some very interesting clinical insights, particularly around the short incubation period of the virus, extremely high viral shedding from the nose, as well as the utility of lateral flow tests, with potential implications for public health,” details about the study published on Imperial College website said.
The study used virus from very early in the pandemic obtained from a hospitalized patient in the ISARIC4C study, prior to the emergence of the Alpha variant.
There were no changes seen in the participants' lungs or any serious adverse events in any participant. All participants will be followed up for 12 months after leaving the clinical facility to monitor for any potential long-term effects.
Participants were exposed to the lowest possible dose of virus found to cause infection, roughly equivalent to the amount found in a single droplet of nasal fluid when participants were at their most infectious.
Peak levels of the virus were significantly higher in the nose than in the throat, indicating a potentially greater risk of the virus being shed from the nose than the mouth. This highlights the importance of proper facemask use to cover both the mouth and nose.
This is the first study that has been able to provide detailed data on the early phase of infection, before and during the appearance of symptoms. While there is a possibility of missing infectious virus early in the course of infection, particularly if only the nose is tested, the researchers say these findings overall support continued use of LFTs to identify people likely to be infectious.
“We found that overall, lateral flow tests correlate very well with the presence of infectious virus,” said Professor Chiu. “Even though in the first day or two they may be less sensitive, if you use them correctly and repeatedly, and act on them if they read positive, this will have a major impact on interrupting viral spread.”
The authors highlight that while the model is a safe and effective approximation of real-world infection in young adults, the small sample size, reduced diversity of infected volunteers and limited follow up period may restrict the findings.
However, they add that despite these limitations, the study has important implications for public health, including around proper mask-wearing, isolation periods for infectious individuals, the use of LFTs, and establishing the human challenge platform to investigate further aspects of COVID-19.
Future work will see the team determine why some people became infected and others did not and develop a challenge virus using the Delta variant, which is already underway by Imperial in partnership with hVIVO and funded by the Wellcome Trust, and which could be used in follow-on trials.
According to the team, with these data supporting the safety of the infection challenge model and a Delta variant available, this could theoretically provide a ‘plug and play’ platform for testing new variants and therapies, including vaccines.
Professor Chiu added: “While there are differences in transmissibility due to the emergence of variants, such as Delta and Omicron, fundamentally, this is the same disease and the same factors will be responsible for protection against it."
"From the point of view of virus transmission related to the very high viral loads, we are likely if anything to be underestimating infectivity because we were using an older strain of the virus. With a newer strain, there might be differences in terms of size of response, but ultimately we expect our study to be fundamentally representative of this kind of infection,” he noted.