5 volunteers exposed to Covid-19 virus in Singapore’s first human trial

Associate Professor Barnaby Young, head of the Singapore Infectious Disease Clinical Research Network (left), with study participant Goh Zhi Hao on March 12. The Straits Times/Asia News Network

SINGAPORE — Five young volunteers here have been deliberately exposed to the Covid-19 virus in the country’s first human challenge study, paving the way for more of such studies to be conducted here to strengthen Singapore’s disease preparedness and response.

Unlike a traditional study, where subjects are infected naturally, a human challenge study intentionally exposes volunteers to a virus in a controlled environment, so that researchers have a better chance of gaining more precise insights about the infectious agent in less time. This can help accelerate the development of vaccines and therapeutics.

The study, known as Sing-CoV, is being conducted at the National Center for Infectious Diseases (NCID). By September or October, the research team aims to recruit for the study a total of 20 healthy people aged 21 to 30 who have already been vaccinated against Covid-19, and follow up with them on five occasions for up to a year.

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While the study will help scientists understand why Covid-19 infections still occur despite previous vaccinations and infections, the authorities’ broader aim is to develop the framework and expertise to conduct future human challenge studies.

“We need to continually strengthen Singapore’s preparedness and response to infectious diseases, including ‘Disease X’, a future disease that could result in a pandemic,” said Professor Vernon Lee, the incoming chief executive officer of the Communicable Diseases Agency (CDA), a new public health agency dedicated to managing communicable diseases, which will be formed on April 1.

He added that the Sing-CoV human challenge study adds a new instrument in Singapore’s toolkit to be better prepared and ready for the next infectious disease challenge, and to develop targeted response measures more rapidly.

Challenge studies are particularly useful for selecting vaccines or treatments to be tested in larger trials, as they can be done quickly and cost-effectively, with fewer participants. The Straits Times/Asia News Network

Future human challenge studies will be conducted by CDA, he said.

Associate Professor Barnaby Young, the principal investigator for Sing-CoV, said having a framework for such studies allows Singapore to next move on to a global Covid-19 challenge project to find next-generation Covid-19 vaccines that can not only prevent severe disease, but also block transmission.

The global project is the Mucosal Immunity in Human Coronavirus Challenge (MUSICC) study. It is led by Imperial College London, which conducted the world’s first Covid-19 human challenge study in 2021, with 36 participants.

NCID, which is conducting the MUSICC study, expects to begin recruitment in the second half of 2025. CDA will coordinate and provide the administrative and laboratory support for this study. Unlike Sing-CoV, which is using the Delta strain, the MUSICC study will test the Omicron BA.5 strain.

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In a human challenge study, participants are intentionally exposed to an infectious agent, such as a virus or bacteria, which would help to answer scientific questions about the agent in a short time, as it requires a smaller number of participants than a traditional study.

It allows researchers to gain more precise insights than a traditional study, where subjects would have been infected incidentally.

Prof Young said: “When we are studying, for example, people with Covid-19… we don’t know how they were exposed, when they were exposed, exactly how much virus they were exposed to, and it’s very difficult to measure those time points afterwards.”

With a challenge study, researchers can also quickly test the effectiveness of new vaccines and therapeutics as the infection is engineered.

In a human challenge study, participants are intentionally exposed to an infectious agent, such as a virus or bacteria, which would help to answer scientific questions about the agent in a short time. The Straits Times/Asia News Network

Traditionally, a vaccine is tested by giving it to people, who are then monitored to see whether they get an infection. There are uncertainties because researchers do not know if they will be exposed or will develop symptoms.

Challenge studies are particularly useful for selecting vaccines or treatments to be tested in larger trials, as they can be done quickly and cost-effectively, with fewer participants, said Prof Young.

He heads a network of physicians at all of Singapore’s public hospitals who conduct clinical research related to infectious diseases. Hosted at NCID, it is called the Singapore Infectious Disease Clinical Research Network.

While human challenge studies may sound dangerous, they are not new and are done carefully with healthy patients, whose safety is prioritized.

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Prof Young said that over the past 25 years, hundreds of these studies have been conducted around the world for a range of infectious diseases, such as influenza, dengue, malaria, cholera and, most recently, Covid-19.

Sing-CoV is the first Covid-19 human challenge study in the world outside of the UK, which launched the world’s first in 2021, followed by two others subsequently.

The Sing-CoV study reimburses participants for their participation in the viral challenge in the hospital ($300 a day), as well as the pre-screening, screening and five follow-up appointments. This adds up to more than $6,000 for each volunteer.

The research team will collect their nose swabs, blood and stool samples, and even expired air, with the help of a machine that participants breathe into and sing to. After the viral challenge in the study, participants will have to make five visits to NCID for follow-up checks.

Out of curiosity, Mr Goh Zhi Hao, 24, who is studying mechanical engineering at Nanyang Technological University, signed up to be the first participant in Sing-CoV, after hearing about it from a friend of a friend who works at NCID.

He was quarantined for 14 days at NCID in September 2024. The experience was “better” than he had expected, he said, as his symptoms were mild and the single room he stayed in was spacious, comfortable and conducive for studying.

A day after a small drop of purified Covid-19 virus was dropped into his nose, he developed sore eyes and fatigue, which lasted for two to three days.

Prof Young said the amount of virus given in the study is the same as that given in the UK Covid-19 study, and the researchers take great care to make sure that participants are exposed to the virus in a safe and controlled environment.

During their stay of up to 14 days, participants are closely monitored by a dedicated healthcare team to ensure they remain well. The risk of developing a severe infection is very small, but should that happen, medical treatment will be given immediately, he said.

Of the five participants who had been inoculated with Sars-CoV-2, only Mr Goh and one other person were infected. The symptoms the volunteers experienced after the exposure were mild, short-lived and did not require any medication, Prof Young added.

“Around 130 people have taken part in Sars-CoV-2 human challenge studies around the world now… and nobody’s had any severe adverse events, nobody has required antiviral medications or developed a severe infection,” he said.