February 2020 | Issue 46
Working on the front line against coronavirus disease

Nicole.jpg By Nicole Lim, Senior Assistant Director, Communications & Outreach

It is 8 a.m. on a Saturday. Dr Julia Ng just arrived for her shift. Instead of heading to the Department of Orthopaedics at Tan Tock Seng Hospital where she has been posted since early January, the junior doctor heads across the road to Basement 1 of the National Centre for Infectious Diseases. She is about to start her shift at the national screening centre, fighting at the coalface of a global disease outbreak.

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Signs direct people to the National Screening Centre located in the National Centre for Infectious Diseases

Dr Ng is among the many doctors, nurses and healthcare workers who have been called to serve the nation at this time of need. Fellow junior doctor Claudia Tong has also been rostered to support this nationwide effort.  

“As doctors, it is our calling to be at the forefront during disease outbreaks and we all have to chip in the manpower now,” Dr Tong said. 

The disease outbreak is, of course, the novel coronavirus, now referred to as coronavirus disease 2019 or COVID-19. It was first detected in the central Chinese city of Wuhan in December last year. This new virus, a close cousin of Severe Acute Respiratory Syndrome, better known as SARS, appeared to have jumped from an animal to humans working at the Huanan Wholesale Seafood Market in Wuhan. The market was known to sell a wide range of animals other than seafood, including badgers, pangolins and snakes. 

The first known case of this novel coronavirus fell ill with unexplained pneumonia on 1 December 2019. By 30 January 2020, just two months later, the virus was detected in every single province—from Tibet to Hainan. 

“The way it spread across the whole of China so evenly, multi-directionally suggests it must have had a quietly growing base before they shut down the live seafood market and controlled the spread,” said LKCMedicine Associate Professor of Infection & Immunity Luo Dahai. “The virus must have quietly established itself in Wuhan for days or even weeks.”

30 January marked another milestone: the total number of people infected with the virus exceeded 8,000, surpassing the number of people in China who came down with SARS. While in Singapore, the Ministry of Health had already confirmed 13 imported cases in the city-state. That same day, the World Health Organization (WHO) declared the outbreak a global health emergency

“During the H1N1 outbreak [in 2009], the WHO was criticised for declaring the emergency too early. When the number of export cases continued to grow and we saw no sign that the epidemic was peaking, that was the right time to declare the emergency,” said LKCMedicine Visiting Professor Annelies Wilder-Smith, an emerging infectious disease specialist.

***

Tracing the source of the virus 

Examining the genetic sequences of the virus, scientists have found few differences between the samples collected so far. As of 10 February 2020, 89 genomic sequences from 13 countries, including three from Singapore, have been released. Since this RNA virus is known to mutate quickly, the close similarity in the sequences indicates that their shared ancestor, or the original patient X, is not in the distant past. 

“The first infection didn’t occur years or decades ago. It probably started in November or December,” said LKCMedicine Associate Professor of Human & Microbial Genetics Eric Yap. “We have not seen many mutations so far and all link back to a large group of common sequences, so it is likely that the infection came from one point source.”

While scientists can’t confirm whether this very first infection with coronavirus disease 2019 or COVID-19 happened at the Huanan Seafood Wholesale Market, the market likely amplified the outbreak through its illegal wildlife trade. 

Tracing the virus’ ancestry further back still, the original hosts are likely to be bats, which don’t get sick from coronavirus infections. 

“All the evidence points to a bat origin for this virus too,” said LKCMedicine Associate Professor of Infectious Disease Yeo Tsin Wen. While he acknowledges that the virus could have jumped straight from bats to humans, this seems unlikely as few bats were traded via the seafood market. This makes another mammalian species a more likely intermediate host. 

Bats were also the origin of SARS and the Middle East Respiratory Syndrome or MERS. The SARS virus jumped from bats to palm civets or raccoon dogs before it was able to infect and spread among humans. MERS is thought to hide out in camels. The latest animal to fall under suspicion for playing intermediary to a coronavirus is the pangolin. Identifying this piece of the puzzle is key to reducing or even eliminating future cross-infections. 

Infectious Disease Consultant A/Prof Yeo said, “It would be good to know which animal was the intermediary host, so you know which animals need to be regulated.”

Upon arrival at the screening centre, Dr Ng, an LKCMedicine graduate, measures her temperature, logging the reading in a shared excel file on the hospital computer system. She grabs a pair of freshly laundered sea-blue scrub pants and a white t-shirt on her way to the changing room. After changing, she stows her belongings in a locker, grabs her protective goggles and heads to the pantry area where the senior emergency doctor leading the shift would brief her and the rest of the team about what to expect and what to take note of. 

Among the most fluid pieces of advice is that the doctors have to be on top of are the criteria that define whether someone is at risk of having contracted the virus. Over the first few weeks alone, these criteria have expanded to ensure everyone at risk is identified promptly. 

While the national screening centre began operating on 29 January, the healthcare community had already been on alert.

“When the first reports emerged from Wuhan of an unnamed virus, we saw the ripple on the horizon and our alert level went up,” said LKCMedicine Assistant Dean for Year 5 Associate Professor Tham Kum Ying, who is also a senior emergency physician at Tan Tock Seng Hospital. 

Even before Singapore confirmed its first case of COVID-19, the emergency department swung into action. 

“Within twenty minutes, we set up the initial ground rules for how to respond via group chat,” recalled A/Prof Tham, adding that half a day later, the operational changes were completed too. This is in stark contrast to the SARS outbreak that struck Singapore in 2003 when communication relied on individual phone calls and emails. New technology gave wings at a time when speed was of the essence. 

Scientific efforts to identify the culprit causing this lung infection, too, were sped up by medical technologies and open sharing of data.

“It took years to confirm that infection with HIV can lead to AIDS,” said LKCMedicine Associate Professor of Infectious Disease Yeo Tsin Wen. “In this instance, we identified the virus within a matter of weeks.”

The whole genome sequence followed soon after. Knowing the virus’ unique genetic traits would allow scientists to quickly develop specific primers to detect the virus and diagnose an infection.  

“The first sequence was published on 10 January, and by the first day of February, 47 sequences were published,” said LKCMedicine Associate Professor of Human & Microbial Genetics Eric Yap. The geneticist is currently developing a low-cost and rapid diagnostic kit for the virus that could be used in areas where access to a large medical laboratory is not possible. 

Keeping a watchful eye on their genetic makeup is particularly important for RNA viruses, the kind of virus the coronavirus family belongs to, as they are notoriously sloppy at copying themselves. And genetic changes could enable the virus to elude tests, become impervious to treatments and vaccines, and spread more easily between humans. 

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Screenshot of A/Prof Eric Yap's Google Site that provides categorised links to reputable sources of information about the virus

These accumulated mutations commonly appear on the outside of the virus. In this instance, they cluster in the spikes, which under the microscope give this virus the appearance of being crowned, leading to the name, coronavirus. 

“When our immune system develops immunity against the virus, those viruses with mutations on the surface may survive better,” said virologist A/Prof Luo.

Like a ship, the virus docks at a pier on the host cell surface, known as the ACE 2 receptor. This receptor is common to many cells and is abundant in the cells lining the airways and lungs. SARS, too, relied on this receptor.

Once docked, the virus flies into the cell’s interior, hijacking the infrastructure to copy itself at a furious pace. Eventually, the cell bursts, releasing lots of new viruses. But in entering the cell, the virus trips the body’s intruder alarm. 

Antiviral proteins attack the virus. Inflammatory cytokines send out an emergency call for backup from immune cells. And it is often when this reaction is out of proportion that people succumb to the virus.

“Some people respond really vigorously because of their own immune system’s overreaction,” said A/Prof Luo, adding that this can lead to a storm of cytokines in the body that causes organs to shut down. 

“But the majority of us have a moderate-level immune response that allows our bodies to kill or eliminate the virus after some struggle,” he assured.

***

At the screening centre, the team of doctors, having been briefed about their shift, step into an antechamber to don the first pieces of personal protective equipment or PPE – an N95 mask and goggles. Once everyone is sure their goggles and mask fit snugly, the group exits the room via another door that leads onto a corridor.  

In that space along with the rest, Dr Ng pulls a pink or white shower cap over her hair. She grabs a black marker pen, a yellow gown and scribbles her name and title in large letters onto the front of the gown. As she and the others slip their arms through the synthetic fibre gown, each of them disappears behind the indistinguishable anonymity of their PPE—save for the scribbled names. 

She pulls on two pairs of blue surgical gloves. Then just before heading to their assigned duties screening either the low or high-risk patients, Dr Ng bags up her handphone and access card in a clear ziplock bag. 

Even these personal belongings need to be protected as the virus can survive outside the body and spread via surfaces. People can also be infected via airborne droplets that enter the body through the mouth, nose and even eyes.

Now ready and protected, the team splits. Dr Ng and her colleagues for the shift walk to the low-risk screening zone. They won’t meet the rest until the end of their shift unless they chance upon each other during a brief moment of respite in the shared pantry. 

Walking into the screening area is much like entering an exam hall. Rows of single desks, each with a chair, fill the room. Between each desk and chair is a two-metre gap to reduce the risk of the virus spreading between people. The doctors move from patient to patient, carefully disinfecting any instruments like stethoscopes, and ensuring the outer gloves are replaced with a fresh pair between each patient. X-rays and blood tests are ordered, results reviewed and patients either released or admitted.

During the early days of the outbreak, Dr Tong described the mood among patients as anxious. The LKCMedicine graduate added that many people had come to be tested on the spot. However, results from testing for the virus are not available instantaneously. Samples have to be sent to a central lab for processing. In the lab, the samples undergo a polymerase chain reaction or PCR to confirm the presence of the virus.  

After the first cluster of local transmissions was discovered on 4 February, the mood changed considerably among patients. Since then, several local clusters have made headlines – erupting anywhere from a five-star hotel to a dormitory and private hire cars. 

“Weekend shifts have become much busier and people are now more worried than before,” said Dr Ng of the mood among the patients she has seen since cases of local transmission were first reported. 

Among the healthcare team, the mood, too, has changed. With the outbreak risk assessment raised to Orange on Friday 7 February, the prospect looms large that teams manning the screening centre are likely facing many more weeks at the front line. Companies and institutions have implemented regular temperature screening at office towers and shared public facilities. Large gatherings and classes have been suspended or moved online. Supermarkets are rapidly restocking shelves and rationing daily essentials. 
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Students queue to have their temperature screened before entering LKCMedicine's Clinical Sciences Building 

Maintaining morale among front line staff while facing a growing outbreak is crucial. To help, senior emergency physicians chip in to maintain an “encouragement fund” that sponsors “unhealthy but happy snacks” for those working at the screening centre, said A/Prof Tham.

“What we learnt from SARS and H1N1 is that morale among the team is very important,” she added. “Staff must be confident in knowing that PPE won’t run out when used as directed, instructions must be timely, clear and actionable, and that their bosses have their backs.” 

***

Dr Ng’s eight-hour shift has come to an end. She hands over to the next team and heads to the corridor to doff – remove – her PPE. Gloves, sanitise hands. Shower cap, sanitise hands. Goggles, sanitise hands. She pulls off the gown and rolls it up like a popiah to avoid accidentally spreading the virus from the gown onto her clean scrubs. The gown joins the rest of the disposable PPE in a biohazard bag. Then she sanitises her hands again.  

To return to the pantry and the rest of the world, Dr Ng has to go through an antechamber. Before she pulls open the door, she checks that no one is unmasked inside the room. Dr Ng enters, removes her N95 mask and washes her hands in the basin. She leaves the room through another door and re-emerges into the regular flow of life.

It is 4 p.m. and the next shift’s turn to continue the work.