NTU experts fighting the COVID-19 pandemic on all levels

Virtual SARS-CoV-2 model. Credit: Fraunhofer Singapore.

[Updated 10 May 2021]

Scientists, clinicians, communications researchers and engineers from across NTU’s schools and institutes are combining their expertise to tackle the COVID-19 pandemic on many fronts.

In this updated and growing list, we highlight our researchers who are making their contribution to Singapore’s fight against COVID-19 in laboratories, through the use of tele-medicine, by working with international partners, and serving on the frontline in our associated hospitals.

 

DIGITAL HEALTH AND TELEMEDICINE DURING COVID-19

Associate Professor Josip Car

Alleviating specific challenges posed by COVID-19, Assoc Prof Josip Car provides health practitioners detailed guidance on implementing and structuring telemedicine consultations for remote patient assessments. During periods of community spread, remote consultations reduce the risk of exposure to infectious agents for vulnerable populations, and help prevent overloading of primary care and hospital systems.

Assoc Prof Car is Director of the Centre for Population Health Sciences and of the World Health Organisation Collaborating Centre for Digital Health and Health Education in NTU’s Lee Kong Chian School of Medicine. He also chairs the School’s Health Services and Outcomes Research programme.

“The challenge of telemedicine is both technical and relational. A successful virtual visit requires technical solutions and procedures to manage the virtual clinic, and more importantly, doctors and patients need to build rapport and mutual trust in such settings,” he says.

Together with colleagues from the University of Oxford in the UK and the National University of Singapore, Assoc Prof Car authored an article that has become the national guideline for treatment of COVID-19 in the UK and in countries that follow the guidance and advice provided by the UK’s National Institute for Health and Care Excellence.

He has also written guides on video consultations for healthcare practitioners in primary and specialist care, and responded to media requests by providing expert opinion and a commentary on COVID-19 from a public health perspective.

“Communicating health matters to the public is a public health measure to provide evidence-based information that is trustworthy. Clear and reliable public communication is particularly critical in times of outbreak to help the nation unite and collectively achieve a societal good,” Assoc Prof Car notes.

 

LINKING INFORMATION WITH BEHAVIOUR

Associate Professor Edson Tandoc Jr

With his background as a former newspaper journalist, Assoc Prof Edson Tandoc Jr of NTU’s Wee Kim Wee School of Communication and Information studies journalism from the perspective of news consumers. He has examined how readers make sense of critical incidents reported in the news and how changing news consumption patterns facilitate the spread of fake news.

In a study based on discussions with young Singaporeans aged 21 to 27 held in February—a month after Singapore saw its first case of COVID-19, Assoc Prof Tandoc and his colleague, James Lee, analysed how the information behaviour of young adults in Singapore shaped their views of disease risks, and in turn their behaviour. Published in New Media & Society, the research showed that rather than actively seeking information about COVID-19, many young adults received information on the disease through scanning news on social media and messaging platforms.

This information-seeking behaviour shaped their view that the virus was only risky for older generations, which led to them not wearing face masks in the early stages of the outbreak in Singapore when this practice was not yet mandated.

“The results document how making sense of what is happening in the early stages of a health crisis can go beyond the disease itself and focus more on social order and information quality, impacting behaviour,” says Assoc Prof Tandoc.

“Shaping young Singaporeans’ initial view that they are not vulnerable to the virus, this process of sensemaking might also explain why some young people—such as those reported in other countries—continued to engage in risky behaviour, like going to the beach or partying, during the pandemic,” he adds.

 

FOLLOWING THE PATH OF THE VIRUS, FROM INFECTION TO PATHOGENESIS

Assistant Professor Sanjay Chotirmall

An expert in respiratory and critical care medicine, Asst Prof Sanjay Chotirmall at NTU’s Lee Kong Chian School of Medicine has been a key author of guidance documents for the clinical management of COVID-19, published by the American Thoracic Society-led international task force. In addition, he was invited at the earliest stage of the pandemic together with colleagues from the USA, Italy and China to co-author a commentary providing clinical and research advice to the global respiratory and critical care community including mapping out a research agenda for COVID-19, published in the Society's flagship journal The American Journal of Respiratory and Critical Care Medicine.

Having been at the Journal’s “editorial” frontline since the start of the COVID-19 pandemic, Asst Prof Chotirmall has written about the unique challenges and issues facing editors at top-tier journals in evaluating emerging science and clinical evidence against the dynamically changing backdrop of a global pandemic. You can read his commentary here.

In a collaborative project with Prof Stephan Schuster of the Singapore Centre for Environmental Life Sciences Engineering at NTU, Asst Prof Chotirmall, Provost’s Chair in Molecular Medicine, is assessing the impact of air quality on clinical outcomes in COVID-19 patients. Using lung organoids (miniature lung-like organ models), and supported by Singapore’s National Medical Research Council under its COVID-19 Research Fund, he is studying COVID-19 pathogenesis to find out how the virus spreads between people, who it particularly infects, and why the airways of people with lung disease such as Chronic Obstructive Pulmonary Disease appear to be especially susceptible to infection. This work includes understanding the inflammatory and immunological consequences of emerging viral variants.

Using a systems biology approach in collaboration with colleagues at NTU's School of Biological Sciences and School of Civil and Environmental Engineering, Duke-NUS Medical School, the National Centre for Infectious Diseases, and a number of hospitals across Singapore, Asst Prof Chotirmall and the team hope to better understand viral infection mechanisms and replication kinetics as well as its immuno-inflammatory consequences in the airways.

 

MODELLING INFECTION PATTERNS

Professor Annelies Wilder-Smith

A clinician-scientist and specialist in emerging infectious diseases, Prof Annelies Wilder-Smith of NTU’s Lee Kong Chian School of Medicine is addressing knowledge gaps and developing policy recommendations for the control of the COVID-19 pandemic. She also serves as a consultant to the World Health Organisation on issues related to COVID-19 vaccine policies.

Her research in the past months focusses on virus transmission risks on flights and cruise ships, and on modelling measures that could help to accelerate re-opening of travel.

 

 

 

 

 

COORDINATING OUTBREAK RESEARCH

Associate Professor David Lye

Assoc Prof David Lye from NTU’s Lee Kong Chian School of Medicine is a senior consultant in the Department of Infectious Diseases at Singapore’s Tan Tock Seng Hospital. He is also the Director of the Infectious Disease Research and Training Office at Singapore’s National Centre for Infectious Diseases.

In his latter role, he coordinates national research efforts on the COVID-19 outbreak, including an outbreak protocol called PROTECT in close collaboration with infectious disease doctors from across Singapore’s public hospitals.

The PROTECT protocol includes guidelines on the collection of clinical samples of COVID-19 patients, which enable several scientific institutions in Singapore to study the biology of SARS-CoV-2, as well as answer questions in genomics, immunology, host susceptibility and antibody response.

The PROTECT group also collaborates with radiologists, intensive care specialists and obstetricians at several national hospitals. Working closely with Singapore’s Ministry of Health, Assoc Prof Lye also helps to ensure that outbreak research is rapid and responsive to the needs of the national outbreak response, and encourages collaborative and non-duplicative research among partners.

Recently bearing fruit is their observational cohort study of COVID-19 patients, published in Clinical Infectious Diseases. Assoc Prof Lye and colleagues in the Singapore 2019 Novel Coronavirus Outbreak Research team found higher amounts of viable virus particles in patients at early stages of the disease. They also discovered that more severe manifestations of the disease in patients were associated with stronger immune response, a finding that may improve doctors’ ability to prognosticate disease development and provide case-specific advice on therapeutic approaches.

In collaboration with US scientists, Assoc Prof Lye contributed to the development of highly potent antibodies that are able to bind the spike protein on the surface of SARS-CoV-2 and prevent the virus from docking onto and infecting cells. Published in Science, the research holds great promise in the development of antibody-based therapeutics for the treatment of COVID-19.

Assoc Prof Lye was also part of a team that developed a simple, robust and fast serological test to detect anti-SARS-CoV-2 antibodies in blood samples, allowing rapid determination of infection rate and herd immunity in populations and helping to shed light on critical questions in antibody protection and vaccine efficacy. Described in a paper published in Nature Biotechnology, the test achieved nearly 100% specificity and sensitivity and could support the wider community in both research and clinical applications.

 

DETECTING AND DIAGNOSING

Associate Professor Eric Yap

Standard testing for presence of SARS-CoV-2 in patient samples requires specialised equipment and reagents and typically takes at least 24 hours from sampling to reporting, hindering swift action to control the spread of COVID-19.

Drawing on his dual backgrounds in medicine and science, and in collaboration with colleagues in NTU’s engineering schools, medical geneticist Assoc Prof Eric Yap aims to overcome the shortcomings of current tests.

“Our goal is to develop ultrafast and automated tests that yield results in minutes, and that can be performed by healthcare workers in the clinic with the same accuracy and sensitivity as in specialised laboratories,” says Assoc Prof Yap, who is principal investigator in the Medical Genomics Lab at NTU’s Lee Kong Chian School of Medicine (LKCMedicine).

Incorporating novel polymerase chain reaction (PCR), microfluidic and optical technologies, his team has been working on accelerating, simplifying and democratising the use of PCR—a core method in molecular biology—in laboratories with limited equipment and capabilities. The researchers developed a protocol for rapid and extraction-free PCR detection of SARS-CoV-2 genetic sequences, which has been published in Genes. A variant of the method has been implemented in the NTU Clinical Diagnostic Laboratory at LKCMedicine, which is headed by Assoc Prof Yap and certified for SARS-CoV-2 testing of clinical samples. As of November 2020, the Lab—which was set up in April 2020 as part of NTU’s response to the COVID-19 pandemic—has tested more than 10,000 swab samples using the direct PCR method and helped to boost national lab testing capacity.

To allow the wider use of COVID-19 testing in countries and regions where laboratory capabilities are limited, Assoc Prof Yap is also working to convert household appliances into portable PCR thermocyclers and to simplify equipment for the detection of PCR-amplified viral genetic material.

 

Professor Shane Snyder

As the Executive Director of NTU’s Nanyang Environment and Water Research Institute, Prof Shane Snyder is using the Institute’s expertise in wastewater management and knowledge of Singapore’s complex sewage collection system to monitor the prevalence of SARS-CoV-2 infection in the population.

“By monitoring sewage from various urban areas or complexes such as residential blocks, dormitories or medical facilities, we aim to rapidly identify COVID-19 outbreaks without invasive procedures involving human interactions, and in a very cost-effective manner,” says Prof Snyder of NTU’s effort in wastewater-based epidemiology—a promising new methodology for early detection of viral outbreaks at the population level.

By advancing the methodology’s sensitivity, Prof Snyder hopes to achieve a warning level for SARS-CoV-2 prevalence of 0.001% or better—a level equivalent to detecting SARS-CoV-2 infection even if there is only one case per 100,000 residents.

“An Australian study, one of the first studies published on SARS-CoV-2 wastewater-based epidemiology, had been able to achieve an estimated warning level of 0.028%, meaning that infection in the population could only be detected if at least one in 3,500 people is infected, “ says Prof Snyder. “To achieve lower warning levels, our research will rely on more sensitive PCR assays covering a wider range of SARS-CoV-2 target genes, studies on the decay of SARS-CoV-2 in wastewater, as well as model optimisation,” he adds.

Prof Snyder, NTU President’s Chair in Water Technologies, previously helped WHO develop guidelines for the production of safe drinking water. As a globally renowned expert on the identification, monitoring and health relevance assessment of emerging water pollutants and pathogens, he has also been consulted by the United States (US) Environmental Protection Agency, US National Academy of Sciences, and US Congress.

 

Professor Duan Hongwei

Harnessing nanomaterials for biomedical applications, Prof Duan Hongwei is developing new technological platforms for early detection and targeted therapy of infectious diseases and cancer.

In collaboration with Assoc Prof Luo Dahai of NTU’s Lee Kong Chian School of Medicine and Prof Lam Yee Cheong of NTU’s School of Mechanical and Aerospace Engineering, Prof Duan has devised a microbiochip for rapid, high-throughput, ultrasensitive detection of SARS-CoV-2 proteins and virus-specific antibodies present in serum and respiratory specimens.

“With our multichannel system, we aim to quantify virus antigen and antibodies of multiple samples simultaneously, using microlitres of specimens,” says Prof Duan, who is the Associate Chair (Research) at NTU’s School of Chemical and Biomedical Engineering. He is currently testing the fully automated device, which can also screen for other pathogens with similar symptoms, such as influenza and dengue, on clinical samples of COVID-19 patients.

In a separate study to tackle the spread of SARS-CoV-2 and other infectious agents via surfaces, Prof Duan is working with Prof Lim Teik Thye of NTU’s School of Civil and Environmental Engineering to develop superhydrophobic—water-repellent—coatings. The biomimetic coatings, which are composed of mussel-inspired adhesive compounds topped by hydrophobic nanoclay particles, can be sprayed on surfaces to make them superhydrophobic, thus repelling virus-harbouring biofluids.

 

Professor Peter Preiser

An expert in malaria biology, NTU’s Associate Vice President (Biomedical and Life Sciences), Prof Peter Preiser, has been studying the complex biological processes involved in the interactions between infectious agents and human hosts for decades.

Leveraging existing research efforts in diagnostics and the collaborative spirit within the Singapore-MIT Alliance for Research and Technology (SMART), where he is co-lead principal investigator of the antimicrobial resistance interdisciplinary research group, his team—in tandem with the group’s second principal investigator Prof Hadley Sikes of Massachusetts Institute of Technology (MIT)—made significant progress in developing a rapid diagnostic test kit for SARS-CoV-2 infection.

“Testing for the SARS-CoV-2 virus is important to complement efforts in the fight against the COVID-19 pandemic,” says Prof Preiser, who is NTU President’s Chair in Biological Sciences and a professor of molecular genetics and cell biology in NTU’s School of Biological Sciences. Probing for virus proteins in nasal and throat swabs or bodily fluids such as saliva or blood, the paper-based biomarker test changes colour from white to blue in as little as ten minutes when SARS-CoV-2 protein molecules are detected.

“The ability to accurately test for the coronavirus nucleocapsid protein, which is observed from as early as day one of disease onset, will allow our rapid diagnostic test to perform first-line screening for the virus, even for mild infections—an important feature that could help significantly in containment efforts,” explains Prof Preiser, adding that the test can be easily administered by anyone with minimal training or need for technical equipment.

Prof Preiser’s team is also developing a serological test that detects antibodies formed against the viral spike protein in blood or serum samples, which would make it possible to screen for past and active cases of SARS-CoV-2 infections in the population.

 

Professor Stephan Schuster

NTU President’s Chair in Genomics Prof Stephan Schuster is Deputy Centre Director (Facilities & Capacities) and Research Director (Meta-’omics & Microbiomes) at NTU’s Singapore Centre for Environmental Life Sciences Engineering.

Working with clinicians at Singapore’s National Centre for Infectious Diseases and the National University Hospital, he leverages his expertise in air microbiome analysis to develop surveillance assays for SARS-CoV-2 virus transmission in hospital wards and other medical facilities where COVID-19 patients are being treated.

“Using state-of-the-art technology such as high-volumetric air samplers including air filters customised for virus collection and direct RNA extraction, we are investigating the transmissibility of SARS-CoV-2 through air,” he says. “The goal is to establish measures that help to keep medical personnel safe,” he adds. First results of the research have been published in Nature Communications.

Analysing human genomic data collected during the pilot phase of the GenomeAsia 100K Project—set up to sequence and analyse DNA samples of a total of 100,000 individuals from across Asia—Prof Schuster (who is the scientific chairman of the international GenomeAsia 100K consortium behind the project) is also investigating correlations between polymorphisms in human proteins that play key roles in the virus’ infection process and people’s susceptibility to catching the COVID-19 disease. First outcomes of the study can be found in Communications Biology.

 

Assistant Professor Tan Meng How

With a background in mechanical and biomedical engineering, Asst Prof Tan Meng How of NTU’s School of Chemical and Biomedical Engineering employs cutting edge technologies, high throughput approaches and engineering principles to investigate gene expression in microorganisms and eukaryotes including humans.

“Testing is key to stopping the spread of SARS-CoV-2,” he says. “However, receiving results through the current gold standard of testing, which is based on Polymerase Chain Reaction technology, takes several hours due to the need for dedicated instrumentation, skilled technicians and time required to transport samples from the collection site to the test facility,” explains Asst Prof Tan, who also has a joint appointment with the Genome Institute of Singapore under Singapore’s Agency for Science, Technology and Research.

Seeking to develop a point-of-care diagnostic test for SARS-CoV-2 that is rapid, sensitive, and specific, Asst Prof Tan is applying CRISPR-Cas gene-editing technology.

“Leveraging the ability of the Cas enzyme to recognise particular viral sequences, we have engineered the CRISPR-Cas system to be able to detect the presence of SARS-CoV-2 at five copies per microlitre within 20 minutes and are currently further improving the assay,” he says.

An article describing the diagnostic assay has been published in Nature Communications.

 

HOW WE HANDLE COVID-19 NEWS

Professor May O. Lwin

Drawing on her experience in health and infectious disease communication, Prof May O. Lwin of NTU’s Wee Kim Wee School of Communication and Information is examining global mainstream media and social media discourse surrounding the COVID-19 pandemic. She also looks into how online communication—in particular related to health messaging and circulation of online misinformation and falsehoods—contributes to public behaviour.

“Our objective is to understand how mainstream and social media are influencing public behaviour during infectious disease outbreaks, especially during the current outbreak of COVID-19,” says Prof Lwin who is also Associate Dean (Special Projects) of NTU’s College of Humanities, Arts, and Social Sciences, and Director of the NTU University Scholars Programme.

Paying particular attention to how mainstream media and the Singapore government are tackling online falsehoods about the disease—including common misinformation and deliberate fake news, disinformation and rumours—she is tracking how the Singapore public engages with both health messaging and falsehoods by monitoring and assessing social media posts and responses.

“Through big data analyses, online risk communication experiments and national surveys, we aim to improve effective health communication to the public as well as to combat falsehoods in the media,” she explains.

Leading the College’s Health, Communication & Society research cluster, and in a collaboration with the National University of Singapore’s Saw Swee Hock School of Public Health, Prof Lwin is also developing a community-based syndromic surveillance system for COVID-19. The system will then be used to model the appropriate response for epidemic aversion and nationwide treatment response during community-wide local transmissions, allowing policy-makers to examine the efficacy of surveillance, importation risk, the potential size of outbreaks and what interventions may mitigate COVID-19 spread.

 

 

ORGANISING THE CLINICAL RESPONSE ON THE FRONT LINE

Associate Professor Tham Kum Yin

Assoc Prof Tham Kum Ying, an Assistant Dean at NTU’s Lee Kong Chian School of Medicine, is an emergency physician in the Emergency Department of Singapore’s Tan Tock Seng Hospital (TTSH), which is at the forefront of dealing with emerging infections and communicable diseases.

TTSH Emergency Department started to install ground rules and operational changes the moment the first reports of the then-unnamed virus emerged from Wuhan, helping the hospital to be ready to face the new challenge even before Singapore confirmed its first case of COVID-19.

“What we learnt from SARS and H1N1 is that morale among the team is very important,” says Assoc Prof Tham. “Staff must be confident in knowing that protective personal equipment won’t run out when used as directed. They should also receive instructions that are timely, clear and actionable,” explains Assoc Prof Tham.