Studying the information conveyed in genes, this scientist recalls the intense days of the pandemic.
“The complication came because we didn’t know very much about this virus,” recalls Dr Eugenia Ong, then a then-senior research fellow with Duke-NUS’ Emerging Infectious Diseases Programme about the early days when the first cases of the novel coronavirus were detected in a family who presented at Singapore General Hospital in January 2020.
Dealing with the unknown, cautiously
Facing a then-unknown threat, Ong, who studies gene expression in human samples in response to infections, vaccines and treatments, worked with the team on how to safely study these samples.
Mitigating steps included treating the samples with heat and “chemical cleans” that killed the virus but kept everything else intact. They also included wearing two sets of gloves, disposable gowns and N95 masks on top of the usual safety gear required in the lab.
While Ong worked out the rapidly growing number of experiments the team wanted to do and responded to a deluge of emails, patient samples kept coming from the hospital.
“So the first few days and weeks, we were just collecting and freezing the samples while we waited for the approvals to come in,” recalls Ong, who is also part of the team at the Viral Research and Experimental Medicine Centre at SingHealth Duke-NUS (ViREMiCS).
Ong and the team froze the samples, ready to be analysed in batches when they had a large enough number of samples.
Once they got the greenlight, they started by studying the gene expression of patients over the course of their illness until they had recovered.
“It is one of the most highly cited papers that I have,” laughs Ong. “It gained quite a bit of traction. There was a lot of interest around what was happening on a molecular level in these patients.”
At the same time, other projects came online with samples from various clinical trials coming in throughout the day.
“It started to feel more intense when we went into the Circuit Breaker,” remembers Ong. “With the split team arrangement, we had to do a lot of coordinating.”
At the same time, Ong was onboarding Ayesa Syenina who had just successfully defended her thesis and was now joining the lab as a full-time staff. Between the two of them, they oversaw the coordination and tracking of clinical trial samples, with Ong taking the morning shift and Syenina covering the afternoon.
“But she really had to hold her own during those days,” says Ong. “We had regular catch-ups in the evening. They were long days.”
The joy of discovery
Mentoring new colleagues aside, Ong and the team were also gearing up to start on the human trials for Singapore’s first locally tested vaccine, which Duke-NUS was co-developing with Arcturus Therapeutics — from having all the necessary reagents and tests ready to spelling out the finer points of how the samples would be transferred between the trial site and the lab.
“Starting on the vaccine project was a nice transition as we had stopped sampling patients from the hospital with numbers so low by then,” recalls Ong.
By National Day 2020, Ong and the team at ViREMiCS were ready. It was the last moment of calm before the storm hit.
“It was pretty intense and intensive after that point in time,” remembers Ong. “We wanted to get everything right. Because, really, with clinical trial samples, you need to get it right the first time.”
The last tube of blood from the final follow-up visit was drawn in January 2021, capping an intense four-month period.
“It was a lot of work, I won’t underplay that,” she says, her tone suggesting that it was also hugely satisfying work.
“We had these moments when we were the first to see results and the patterns that emerged,” offers Ong by way of explanation.
Bringing discovery to benefit testing science
“What is interesting is the contrast between this virus versus SARS,” muses Ong.
“I remember SARS, because I was in secondary school then. We got an extra week of June holidays because they were trying to keep everyone at home.”
“That disease was more severe,” Ong continues. “Because of that, more people died.” Bringing that virus to a hard stop.
“SARS-CoV-2, though, was a different beast. There was a lot more effective transmission that we were seeing with the variants that were coming up,” explains Ong. “And the question was: Would the vaccines protect against these variants?”
For Ong, that question led to further investigations into the immune response and whether it differed between vaccination and infection; and whether age, gender and health mattered.
“We started a follow-up study with some of the participants from the Phase I study to look at long-term immunogenicity from the vaccine, looking specifically at T-cell responses to find out how long these responses actually last,” explains Ong.
“In parallel, we were also looking at healthcare workers who received the mRNA vaccine,” she adds, explaining that they were tracking the incidence of side effects and investigating the molecular triggers behind them.
“Running these in parallel allowed us to really dissect what happened at the molecular level in participants.”