As part of our series, ‘Research in the time of a pandemic’, we are talking to researchers and other key stakeholders involved in the battle against COVID-19 across the globe to better understand the work they are doing, how it contributes to humanity’s collective efforts to find a solution, as well as deciphering all aspects of the research underway to understand it for what it is— a human endeavour
This week’s guest is Dr. Lee Kwan Hyi, Principal Research Scientist in The Center for Biomaterials at Korea Institute of Science and Technology (KIST) and a Professor in the Department of Biomedical Engineering at the Korea University of Science and Technology (UST). Dr Lee discusses the role that science, cooperation, transparency, data and information sharing have in informing government policies and shaping one of the most successful COVID-19 responses globally so far, led by South Korea. Moreover, he gives us his predictions about the future and the possibility of new pandemics as well as shares insights into his latest research project, focusing on identifying asymptomatic cases of COVID-19 through a highly sensitive electrical sensor.
The response from the Korean research community was initiated independently from multiple institutes, with different approaches. There is a large research center, the ‘Center for Convergent Research of Emerging Virus Infection’(CEVI), led by The Korea Research Institute of Chemical Technology (KRICT). CEVI was founded at a multi-institutional level in 2016. They are working on various topics regarding COVID-19. In the largest multidisciplinary national lab, The Korea Institute of Science and Technology (KIST), the initial response was at an institutional level. Each specialized research team has been working on diagnosis, vaccine, and disease spread simulation encouraged by the president and the board of directors. Of course, individual efforts from research groups in universities should be mentioned, too. For example, the research team led by professor Narry Kim at Seoul National University revealed the high resolution genetic map of SARS-CoV-2 for the first time.
Soon enough the research community realized that close cooperation at the whole country level is indispensable to effectively respond to the pandemic. Putting different institutions together, however, was not a simple task. Fortunately, presidents of national laboratories in Korea promptly held a meeting to discuss the important matters regarding COVID-19. In the meeting, challenges were identified, and possible collaborations and cooperation strategies were actively discussed. This meeting allowed each institute to focus on the topic of their specialty.
"...the research community realized that close cooperation at the whole country level is indispensable to effectively respond to the pandemic."
We are focusing on a COVID-19 diagnosis for those who do not show any symptoms. We now know that there are significant number of asymptomatic patients that can spread the disease. In addition, COVID-19 can potentially spread even during the incubation period, unlike other viruses. Accordingly, a highly sensitive sensor that can identify people without symptoms is needed. Our team has been recognized as a research group developing a highly sensitive, stable, and reproducible electrical biosensing platform for a clinical diagnosis. We have successfully diagnosed various diseases including prostate, colon cancer, and avian influenza virus. We recently reported the portable form of our electrical sensor. Its robust onsite performance was validated at the biosafety Level 3 for avian influenza virus detection. With this background, we are currently developing a highly sensitive electrical sensor to quickly identify people without symptoms. The idea is to detect a trace amount of spike proteins of SARS-CoV-2 from clinical specimen. Due to the difficulties of dealing with the real SARS-CoV-2, we synthesized a pseudo-virus with a microfluidics device to design our sensing platform before validating it with the real SARS-CoV-2.
There are opportunities despite how much we don’t know about the virus. Identifying the genetic sequence of the virus is in general accurate and specific. However, the capacity of such a diagnostic system is limited by the amount of equipment and number of experts available to operate. I think the next chance we will have is with simple test kits utilizing proteins to quickly screen people that are negative to the virus. Such a test should be i) simple, ii) with a large test capacity, iii) accurate, iv) portable, v) fast, and vi) cheap. One example is a sensor utilizing antibodies to capture spike proteins. This type of test can also be used to monitor herd immunity, too. As for all immunoassay based biosensors, its performance however depends on the antibody, which takes some amount of time to produce. Therefore, a sensor that does not require a synthetic antibody will hold a great merit, too.
"...we are currently developing a highly sensitive electrical sensor to quickly identify people without (COVID-19) symptoms."
The best action, if I could choose one from the government’s initiatives, is sharing information transparently. COVID-19 is caused by a new virus with unprecedented spreading power. Accordingly, multiple conspiracy theories for COVID-19 were generated, and spread widely. The wrong information raised anxiety, imposing a challenge on people complying with the government policies. This led to panic buying of foods and failure of social structures. In this aspect, the openness of sharing disease statistics every day (it was even twice per day at early stages) was the foundation of every policy that followed. Other important policies were also critical in controlling the pandemic. To expedite the diagnosis for large amount of people, the government in South Korea shortened the approval process for COVID-19 diagnosis kits. In addition, the government re-distributed the research funds to accelerate the translation of research into commercial products for onsite use.
All of the aforementioned actions were only possible through the deep cooperation from all stakeholders including researchers, clinical experts, and most importantly, the public. In regards to the country’s travel approach, we did not block people from overseas. We trusted that our system could handle the influx of people. We accommodated them into our well-organized disease controlling infrastructure. Due to the success of the diagnostic kit developments from several companies, we were able to help many countries in need by supplying the kits.
"...the openness of sharing disease statistics every day (it was even twice per day at early stages) was the foundation of every policy that followed."
In fact, the radical situations drove the policy changes quite dramatically. For example, due to the limited capacity of hospitals, Korea’s Center for Disease Control and Prevention devised an innovative concept: the ‘drive-through test’. The urgent need for an accurate diagnosis system shortened the approval process for diagnostic kits. Our country also started social distancing and many companies and institutes including KIST actively participated and encouraged homeworking. I should mention that our country has been suffering from fine dust for years. A lot of research have reported the harmful effects of fine dust. The only practical solution for Korean people was putting on a mask, and it became the norm in Korea. Naturally, almost all people in Korea have been using a mask long before the pandemic started and this plays an important role in the prevention of COVID-19 spread.
"...the radical situations drove the policy changes quite dramatically."
I cannot emphasize enough the importance of sharing information and data regarding virus. Without sharing information and data openly, duplicate research is inevitable. Duplicating the research in this pandemic situation is a serious waste of resources and responsibilities. Not sharing information and data would only slow down our reaction to the pandemic. No one can start their research from scratch. The current research is based on the previous results reported by many others. For example, we need to know the sequence of mRNA of SARS-CoV-2 to design a primer for PCR test. A protein structure is also needed to synthesize an effective antibody for immunoassay tests. Based on these studies, one can start to build a sensor system that can be used onsite.
"Duplicating the research in this pandemic situation is a serious waste of resources and responsibilities."
The first wave of COVID-19 will end in a couple of months. However, many experts in the COVID-19 related fields predict that a next wave of COVID-19 will come as early as this winter with increased fatality. This is a terrifying fact. To handle the upcoming pandemics, the development of robust infrastructure, taking decisive actions without social and economic failure are necessary. One way of preparing for this is to develop a drug and a vaccine. Currently, about 80 groups around the world are developing vaccines and it will become available by mid-2021. Recently coronavirus drug, Remdesivir, showed positive results from the Phase 3 trial. Due to limited resources, however, the drug will not be available for all of those who are in need. Also, we cannot exclude the possibility of a mutation. These uncertainties clearly represent the needs to develop a diagnostic system with a large capacity. For researchers, a groundbreaking diagnosis, treatment, and vaccine ideas to take actions in a timely manner are necessary.
" I can imagine that our future will continue to see pandemics more frequently."
We suffered from multiple coronaviruses causing SARS (2002), MERS (2015), and COVID19 (2019). The frequency of new viruses is increasing. This means we probably have more diseases like COVID-19 in our near future. I can imagine that our future will continue to see pandemics more frequently. Without the robust infrastructures, the social and economic failure that we are suffering now will be repeated. Thus, the preparation of future pandemic through a close cooperation among stakeholders is the foremost action we need to take.
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Dr Lee Kwan Hyi is a Principal Research Scientist in the Center for Biomaterials at Korea Institute of Science and Technology (KIST) and a Professor in the Department of Biomedical Engineering at Korea University of Science and Technology (UST). He is an Expert committee member of the National Technology Level Evaluation in Korea Ministry of Science and ICT (Biochips and Biosensors). He obtained his BS (1996) and MS (1998) from Yonsei University, Seoul (Korea), and his PhD in 2010 from the Johns Hopkins University, Baltimore in the USA. He visited the institute for Nanobiotechnology at the Johns Hopkins University in 2013 and the Department of Chemical and Biomolecular Engineering at the University of Illinois at Urbana-Champaign in 2018-2019 as a visiting Professor. His research involves utilizing nanodevices and nanomaterials for sensitive accurate detection of genetic/proteomic biomarkers and viruses, and bridging nanotechnologies to the on-site applicable technologies at clinics. He has carried out leading roles in the clinically translational research projects such as highly sensitive detection of avian influenza viruses, non-invasive diagnosis of prostate cancer via patient urines, diagnosis of colon cancer and pancreatic cancer from patient serum.
Dr Lee is also writing a book titled ‘Biomedical nano-Monitoring’ with Springer Nature and has published with Nature and Springer. Some of his publications include, ‘Tailoring H2O2 generation kinetics with magnesium alloys for efficient disinfection on titanium surface’ and ‘Overview of current standpoints in profiling of circulating tumor cells’.