Doses, Distance, and Data: The Road to Safe Travel

Local pharmaceutical firm Golden Biotechnology Corp. independently developed Antroquinonol (Hocena®), a novel small-molecule drug, and is now testing its use for treatment of COVID-19. Photo: Golden Biotechnology Corp.

Despite rigorous border control and strict measures, COVID-19 has made its way into Taiwan. Now businesses, researchers, and government are working on innovations that will put Taiwan back in business.

Until recently, Taiwan had a remarkable success record in containing the spread of COVID-19 and maintaining normality for its citizens. While hospitals worldwide had their capacities stretched to their limits, Taiwan reported approximately 1,200 local cases and 11 related deaths in 14 months. However, in May, a few local clusters resulted in a significant spread of the coronavirus around the island.

The sudden surge in cases – roughly 200-400 per day – caused the Central Epidemic Command Center (CECC) to raise the pandemic alert for the greater Taipei area and later the whole island to Level 3, shutting entertainment establishments, schools, and many offices.

The outbreak has had a major impact on the island’s tourism and recreational industries, which were previously suffering the effects of the pandemic. International arrivals in 2020 were down by 88% from 2019, and hotels, amusement parks, and theaters experienced massive losses last year. Since May, Taiwan has amplified its efforts to combat the virus and adjust to life with COVID-19, utilizing medical science and technology to adapt. 

Scrambling for vaccines

Due to the government’s swift reaction to the pandemic, resulting in few local cases, Taiwan residents were initially hesitant to sign up for vaccines. Concerns related to rare fatal blood-clotting incidents and a preference for Moderna and Pfizer’s mRNA vaccines also contributed to the slow uptake of the approximately 316,000 AstraZeneca vaccines offered during the early spring of 2021. But the gravity of the May outbreak has swayed public opinion and largely shifted the issue from one of demand to supply.

Following an initial struggle to obtain vaccines, the Ministry of Health and Welfare has signed contracts to procure close to 20 million doses of foreign vaccines, including 5.05 million doses of Moderna, 10 million AstraZeneca, and 4.76 million unspecified brands through the international COVAX program. Additionally, the U.S. provided Taiwan with 2.5 million doses of the Moderna vaccine, which arrived in Taipei on June 20. Japan contributed 1.24 million vaccine doses to Taiwan and Lithuania 20,000 doses.

As Taiwan continues its quest for foreign vaccines, Taiwanese biotechnological companies Medigen Vaccine Biologics Corp. (MVC) and United Biomedical (UBI) are undergoing their second-phase clinical trials for domestically produced COVID-19 vaccines. The Center for Disease Control (CDC) on May 28 signed contracts to procure a minimum of 5 million doses from each of the two companies.

MVC, a biopharmaceutical company focused on developing and commercializing novel vaccines, received the interim analysis results of its Phase II clinical trials in June and plans to produce 5-10 million doses during 2021 if the vaccine receives final approval.

Paul Torkehagen, director of MVC’s international business department, says that the company’s second-phase clinical trials involved over 3,800 individuals – around 10 times the average number of participants used in such trials.

“It gives us a pretty good idea of the safety and the potential efficacy of our vaccine,” says Torkehagen. “Of course, the vaccine is still being evaluated by the Taiwan regulatory health authorities. Once they have evaluated the data, they will share it with us, and if there’s a high level of efficacy, we expect to be granted an EUA [Emergency Use Authorization].”

MVC produces an adjuvanted subunit COVID-19 vaccine. Unlike Moderna and Pfizer’s mRNA vaccines and AstraZeneca’s adenoviral vector vaccine, adjuvanted subunit vaccines produce spike proteins for boosting the immune system in a bioreactor rather than inside the body. This means the body only needs to neutralize the injected spike proteins rather than manufacture the proteins itself, Torkehagen explains. These types of vaccines have historically been more effectual for individuals who are immunocompromised or have severe allergies.

“We still need to prove this in further comparisons and clinical trials,” notes Torkehagen. “But the safety data provided in our second phase of clinical trials show that systemic adverse events and local reactions are usually mild. And 3,800 individuals give you quite statistically significant data.”

Although Phase III trials are ordinarily used for determining efficacy, the Taiwan Food and Drug Administration has decided to allow second-round trial results to be analyzed via immunobridging. This approach uses the immune responses measured in clinical trial participants to judge the vaccine’s overall efficacy.

Charles Chen, president of MVC, says he is grateful for the government’s cooperativeness during the company’s development of its COVID-19 vaccine. Photo: MVC

MVC President Charles Chen stresses that no serious adverse events have been recorded during Medigen’s Phase II clinical trials. Additionally, says Chen, less than 1% of the participants experienced a fever following injection, indicating high levels of safety.

During the development and testing of MVC’s vaccine, the company met with relevant authorities weekly for over a year and the vaccine has been subjected to a rolling review.

Chen stresses the critical role this regimen has played in the development of the vaccine: “The authorities have guided us in the right direction. That has been really important, especially considering a prospective EUA. We have to know what kind of regulations we need to meet and what kind of data we should provide.”

Improving healthcare

Although vaccines reduce the infectiousness and fatality rate of the coronavirus, new viral variants are more transmissible and could be resistant to current vaccines. Furthermore, vaccinated travelers could still spread the virus and circulate new strains of COVID-19.

Taiwanese biopharmaceutical company Golden Biotechnology Corp. is highly aware of the importance of providing innovative solutions for coronavirus treatment. The company has approached completion of its Phase II clinical trials in the U.S., Peru, and Argentina for COVID-19 treatment using the drug Antroquinonol (Hocena®).

Golden Biotech purifies Antroquinonol from Antrodia camphorata, a mushroom used as a traditional Chinese herbal medicine. Antony Lee, Golden Biotech’s corporate development manager, notes that according to current findings, Antroquinonol has anti-virus, anti-inflammatory, and antibiotic features, producing several possible positive effects against coronavirus strains. The company expects that the drug will alleviate coronavirus symptoms and minimize the potential side effects of the treatment process.

“As of now, there is no single drug on the market that can simultaneously fight the COVID-19 virus as well as the symptoms,” says Lee. “When you combine several drugs, you also put patients at higher risk of adverse effects. Antroquinonol exhibits positive efficacy with low toxicity and has so far shown few adverse effects, which means that we expect it to be safer to use – particularly for older patients and those who already take other medications.”

The Phase II clinical trials for Antroquinonol involves 174 patients. The trial is a randomized, double-blinded, and placebo-controlled study of the safety and efficacy for hospitalized patients with mild to moderate symptoms. Initial results of the trials have received a positive response from the Data Monitoring Committee (DMC), an independent body approved by the U.S. Food and Drug Administration (FDA). DMC also suggested that the study be expanded to severely ill hospitalized COVID-19 patients on non-invasive ventilation or high-flow oxygen.

Early, accurate, and efficient detection of COVID-19 is critical to saving more patients’ lives. In May, Taiwan AI Labs, a Taipei-based privately funded research organization, received FDA approval for an AI-based system that uses chest x-ray images to predict whether a patient is infected with the coronavirus. This method has already been integrated into the screening system for COVID-19 and reaches an 80% specificity.

Taiwan AI Labs’ AI x-ray-screening tool can detect the presence of COVID-19 quickly and with high accuracy. Photo: Taiwan AI Labs

“We’ve been developing this system since January 2020,” says AI Labs founder Ethan Tu. “At the time, we were studying pneumonia detection by chest x-ray. When COVID-19 started to spread, the director of CECC asked if we could use our system to detect the coronavirus. We quickly started to train our system to detect COVID-19 instead.”

With funding from the Ministry of Science and Technology (MOST), the private research organization has also developed a COVID-19 collaborative platform for repurposing existing drugs for new applications. The project is a collaboration with National Taiwan University, National Yang Ming Chiao Tung University, and Academia Sinica. AI Labs’ system uses bioinformatics technology to simulate and predict the binding affinity of the target proteins and drug compounds of drugs known to be clinically safe. Results are published as the DockCoV2 database, which is available to the global medical research community.

Curbing the spread

Taiwan has applied technological solutions to combat the spread of COVID-19 throughout the pandemic, and the number of digital tools available has grown exponentially since May. To trace contacts while avoiding violations of personal data protection rights, Taiwan’s Executive Yuan on May 19 launched a real-name registration system that uses QR code scanning via smartphones to register visitors to restaurants, convenience stores, and other business establishments.

Additionally, Taiwan AI Labs launched the Taiwan Social Distancing App, which leverages Bluetooth signals to estimate users’ physical interactions. The application will send push notifications if a user has been less than two meters from a confirmed case for more than two minutes. The data is stored with anonymous hashed ID history at each device for a maximum of 28 days.

The Taiwan Social Distancing App, which is available in both English and Chinese, performs contact tracing while protecting the privacy of its users.

If a new case is confirmed, the health authorities assign a verification code to confirmed cases, which they enter before the app notifies contacts. Those who receive a notification are not told the identity of the confirmed case, and the case will be unable to see who was contacted. Those exposed are then advised to contact the CECC’s 1922 hotline to report the exposure.

For AI Labs’ Tu, protecting privacy is of the highest priority. “When we set up AI Labs, we worked from the principle that we need to respect privacy and integrity when we develop an algorithm,” he notes. “And when we initiated discussions with the CECC last year, we wanted to track contact history while protecting privacy. Since Bluetooth signals let us know about the devices around us, we decided to leverage Bluetooth signals to develop a decentralized system. With this system, people can track devices nearby instead of having the government track their devices for them.”

More than eight million users in Taiwan have downloaded the app. Although the application was ready in early 2020, widespread uptake did not begin until the recent outbreak on the island.

“When we developed the social distancing app during March last year, it became a kind of open-source project,” says Tu. “There was no real need for it in Taiwan at the time, so we put the project on hold, but we also contributed our source code to other countries so they could make their own social distancing apps.”

Tu further notes that a vaccine reservation system is being developed under the supervision of Minister Without Portfolio Audrey Tang. Once vaccines become available to the public, people can reserve them online using their National Health Insurance app or at pharmacies and supermarkets, in a procedure resembling the mask reservation system set up in 2020.

While those hoping to vacation in Taiwan will have to wait a while longer, these innovations are strides in the right direction. By utilizing vaccines, contact tracing, rapid diagnoses, and effective treatment, the new normal – while vastly different from the past – will assure a higher degree of safety.

To assist further discoveries related to the pandemic, MOST’s National Applied Research Laboratories (NARLabs) is inviting researchers from industry and academia to submit applications to access its new Taiwania 3 supercomputer for research projects aiming to combat COVID-19. Applications to access Taiwania 3 are open until July 31.

Shepherd Shi, director general of NARLabs’ National Center for High-performance Computing (NCHC), says that Taiwania 1 and 2 had been used to develop several new applications, including a COVID-friendly, AI-powered stethoscope equipped with a microphone.

“Our primary mission is to support academic researchers and universities with medical research,” says Shi. “But because of the pandemic, we opened our resources to industry users to enable more discoveries.”

Taiwania 3 is NARLabs’ latest scientific and technological contribution to medical research. It is a CQ-based supercomputer that can be used for drug development and other research to gain a more profound knowledge of the virus.

Shi explains that NCHC has upgraded the supercomputer’s capabilities by partnering with Illumina, a U.S. company that makes genomic sequencing machines. Users of Taiwania 3 will be able to utilize Illumina’s proprietary coronavirus sequencing service COVIDSeq to perform virus analysis.

In an emailed statement to TOPICS, MOST provided further explanation of the areas where Taiwania 3 can assist.

“Because of the pandemic, we have a better understanding of the importance of digital tools to promote health,” MOST said. “We welcome applications that include the Internet of Things (IoT), blockchain, cloud computing, artificial intelligence, and 5G. These digital core tools are where NARLabs can help companies develop innovations to fight the virus.”