Singapore has successfully initiated its first COVID-19 human challenge study, deliberately exposing five young volunteers to the SARS-CoV-2 virus under controlled conditions. The groundbreaking trial, known as Sing-CoV, is being conducted at the National Centre for Infectious Diseases (NCID) and represents a significant advancement in the country's infectious disease research capabilities.
Controlled Viral Exposure Under Strict Safety Protocols
Unlike traditional clinical trials where participants may naturally encounter pathogens, the human challenge model directly exposes volunteers to a specific viral dose in a carefully monitored environment. This approach allows researchers to precisely track infection dynamics from the moment of exposure.
"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," explained Associate Professor Barnaby Young, principal investigator for the Sing-CoV study.
Of the five initial participants who received controlled nasal drops containing purified Delta variant SARS-CoV-2, only two developed infections. The symptoms reported were mild and transient, requiring no medication. One participant, 24-year-old Nanyang Technological University student Goh Zhi Hao, experienced sore eyes and fatigue lasting 2-3 days following exposure.
"The experience was better than I had expected," said Goh, who was quarantined for 14 days at NCID in September 2024. "My symptoms were mild and the single room I stayed in was spacious, comfortable and conducive for studying."
Comprehensive Data Collection and Participant Monitoring
The research team is collecting extensive biological samples from participants, including nose swabs, blood, stool samples, and even expired air using specialized breathing and singing equipment. Participants undergo a 14-day observation period at NCID followed by five follow-up visits over the course of a year.
Safety remains paramount in the study design. Participants are continuously monitored by dedicated healthcare teams, with immediate medical intervention available if needed. The viral dose administered matches that used in previous UK-based COVID-19 challenge studies, which have demonstrated strong safety profiles.
"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," Prof Young noted.
The study provides substantial compensation to volunteers, with participants receiving approximately $6,000 for completing the full protocol, including $300 per day during hospitalization plus additional payments for screening and follow-up visits.
Building Framework for Future Pandemic Preparedness
By September or October 2024, researchers aim to enroll a total of 20 healthy individuals aged 21-30 who have previously received COVID-19 vaccination. While the immediate scientific goal is understanding breakthrough infections in vaccinated individuals, the broader strategic objective is establishing expertise and infrastructure for future 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, incoming CEO of the Communicable Diseases Agency (CDA), a new public health entity launching April 1st that will oversee future human challenge studies.
Global Collaboration and Next-Generation Vaccine Development
The Sing-CoV trial positions Singapore as only the second country globally to conduct COVID-19 human challenge studies, following the United Kingdom's pioneering work in 2021. This achievement enables Singapore's participation in international research initiatives, including the upcoming Mucosal Immunity in Human Coronavirus Challenge (MUSICC) study.
Led by Imperial College London, MUSICC aims to develop next-generation COVID-19 vaccines capable of not only preventing severe disease but also blocking transmission. Unlike Sing-CoV which utilizes the Delta variant, MUSICC will test the Omicron BA.5 strain. NCID expects to begin recruitment for this global initiative in the second half of 2025, with CDA providing administrative and laboratory support.
Human challenge studies offer significant advantages over conventional clinical trials, particularly for infectious disease research. They require fewer participants, provide more precise data, and can accelerate therapeutic development timelines. This approach has been successfully employed for decades in studying diseases including influenza, dengue, malaria, and cholera.
"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," Prof Young explained. As head of the Singapore Infectious Disease Clinical Research Network, he coordinates clinical research efforts across all of Singapore's public hospitals.
The successful implementation of Sing-CoV represents a significant milestone in Singapore's biomedical research capabilities and pandemic preparedness strategy, establishing critical infrastructure that will enhance the nation's ability to respond rapidly to future infectious disease threats.
