Genome researcher seeks to boost targeted treatment for COVID-19

7 January 2021

While the rollout of COVID-19 vaccines dominates the news, the quest for better treatments for this virus and other infections is continuing apace.

Dr Andrew Kwok (Croucher Scholarship 2018) has joined this endeavour, as a DPhil researcher with a leading University of Oxford research group working for better outcomes in treatment of infectious diseases.

While he believes that vaccine researchers are doing a crucial job, the importance of his research cannot be underestimated, with COVID-19 likely to be part of life for many years.

Supervised by Julian Knight, Professor of Genomic Medicine in the Wellcome Centre Human Genetics, his laboratory team is exploring how treatments can be more successfully targeted based on greater knowledge of the individual host.

Kwok said they wanted to understand heterogeneity within COVID-19 patients. “It’s the same infection, but people have different outcomes, so there must be a huge part to do with the human host. We look at the host and why some people have a bad outcome while others have a good outcome.”

Steroids are a key part of existing treatments, but other drugs that have been tested have shown conflicting results in COVID-19 patients. If doctors better understood patients’ individual immune responses and profiles, they may be able to target treatments, he explained.

“We can imagine a scenario in the future where what our research would be able to do is to run a relatively simple bedside blood test to find out which molecular subgroup this patient falls into. Then we can quickly make treatment decisions.”

However, Kwok emphasised that such a test is some years away. His laboratory would not undertake human trials – other researchers would do that – and they are at least two years away, he estimated.

The laboratory was already working on susceptibility to infectious diseases, particularly sepsis, with Kwok investigating the genomic response to sepsis for his DPhil. He was lead author of a Nature Reviews Genetics article published in late 2020, which noted: “Understanding how human genetics influence infectious disease susceptibility offers the opportunity for new insights into pathogenesis, potential drug targets, risk stratification, response to therapy and vaccination.”

With new infectious diseases emerging and a growth in antimicrobial resistance, the need for such work was expanding, with the challenge to translate the wealth of data about human susceptibility and responses to infectious diseases into a clinical benefit, it said.

The team segued into its parallel and complementary COVID-19 research early in 2020, with Kwok key in setting up the project. The aim: to compare the immune response of severely ill COVID-19 patients with those suffering from severe influenza or bacterial sepsis and to ascertain why some become much sicker than others.

The project followed talks with existing collaborators in China in January 2020, as the virus began taking hold there. “It spread quite quickly throughout the world and we realised it might hit the UK quite soon. So when the wave hit, we were ready in terms of what experiments we might do,” he recalled.

Dealing with samples from patients with such a contagious disease raises researcher safety issues. “In the early months of the pandemic, we had to figure that out. [There] was a huge amount of work on risk assessment for the lab. The information was not necessarily super-clear because it was at the very beginning of the pandemic,” Kwok said.

That meant full biosafety lab training, but ultimately that training was not tested. “We figured out that the blood samples weren’t infectious but it took a lot of time to do that.”

While Kwok has now put down the pipette and is busy analysing the data generated – he had to learn coding from scratch in the first year of his doctorate – his CV suggests he should be the one administering treatment. He decided to become a doctor while a student at Hong Kong’s German Swiss International School and undertook pre-clinical training at the University of Cambridge and clinical training at the Chinese University of Hong Kong (CUHK).

But he became interested in research after his first year of undergraduate studies, while undertaking a summer internship at the laboratory of Professor Kathryn Cheah Song Eng. Cheah, Chair of Biochemistry at the University of Hong Kong, was a Croucher Senior Fellow in 2000.

Kwok applied for his doctorate within months of graduating from CUHK, during his year on Hong Kong hospital wards qualifying to practice.

“As a junior doctor and at the end of clinical school, I got interested in severely ill patients in acute settings, so I thought maybe I should do intensive care,” he recalled. “Nothing sets you up for the real thing like when you see it as a junior.”

The work of Knight’s laboratory on severe infections attracted Kwok, who won five gold medals during clinical school and obtained triple first class honours at the University of Cambridge, where he studied on a Jardine Foundation full scholarship.

It is an impressive resume and his current research is potentially life-changing. Ultimately, he wants to practise medicine again, but to combine that with clinical research, as does Knight, a renowned clinician scientist. Balancing the two is not uncommon in the UK and the US, but less so in Hong Kong, said Kwok, who is mid-way through his DPhil.

Kwok, who believes the human perspective is important in biological and biomedical research and translating it into “actual human outcomes”, knows this would be challenging. “You are trying to do two intense jobs,” he said. He has had conflicting advice from two noted scientists. One told him: “You should not be motivated by any emotion in the science.” But another, a clinician by training, said her motivations were emotional. “She found her drive that way. It could be that the emotional aspect isn’t necessarily mutually exclusive.”

It’s a conundrum he will need to come to terms with. Undoubtedly, cheesecake will be involved in making the decision. Kwok, a keen baker, credits it with keeping him sane during lockdown, when he learned to make four kinds of cheesecake.

So is he a candidate for The Great British Bake Off television show in future? “I don’t have any plans to do that,” he said, then added, “but I wouldn’t rule that out as a bit of fun.”

Dr Andrew John Kwok completed his pre-clinical medical education at the University of Cambridge in 2014 and finished his clinical training at the Chinese University of Hong Kong in 2017. In 2018, he began his DPhil at the Wellcome Centre for Human Genetics at the University of Oxford, under the supervision of Professor Julian Knight, and with the support of a Nuffield Department of Medicine Prize Studentship and a Croucher Foundation Scholarship.

To view Dr Kwok’s full Croucher profile, please click here