As the first cases of a novel coronavirus were detected in Singapore, a team of clinician-scientists from Duke-NUS and the Viral Research and Experimental Medicine Centre at SingHealth Duke-NUS (ViREMiCS) closely tracked patients’ immune response to help shed light on how this virus interacts with the human immune system.
“By this time, we knew it was a fairly severe disease,” recalls Professor Ooi Eng Eong, from Duke-NUS’ Emerging Infectious Diseases Programme who co-leads ViREMiCS.
“And I thought the first thing we could do is to just find out why some people developed very severe disease while others had only mild symptoms.”
Studying blood and throat swab samples from three SARS-CoV-2 patients, Ooi, who was joined by then-Senior Research Fellow Dr Eugenia Ong, and then-Associate Professor Jenny Low, tracked these patients’ inflammatory and immune responses.
But unlike many other studies carried out around the same time, which would take snapshots at fixed time points, the team decided to collect samples every day.
“We looked at the genes that were turned on or off and whether that could be the underlying reason why some people go on to develop severe disease while searching for some starting points for therapeutic approaches,” Ooi explains.
So they looked at trends in inflammatory responses such as changes in gene expression, levels of cytokines, T-cell responses and viral clearance as well as the impact of re-purposed existing anti-inflammatory treatments on the course of the infection.
“We were able to get a nice pattern of what the immune response looked like,” says Ong. “We detected pro-inflammatory signals through gene expression profiling that correlated with the severity in clinical outcomes, showing that inflammation was a key driver in disease severity.”
With so little known about the virus, they decided to submit their observations on 1 March to Cell Host & Microbe, which would go on to publish the report a month later. It was one of the first — if not the first — paper to do that.
What was the biggest takeaway from that work?
“That the whole process is very dynamic,” says Ooi. “And that we needed to be a lot more specific about what we’re talking about instead of lumping everyone into the same bucket.”