• Several Covid-19 clusters have emerged here in recent weeks
• The authorities said investigations are still ongoing on how the outbreaks began 
• Experts said it may take weeks for investigations to conclude
• They also said that the first reported case may not be the source of the infection

SINGAPORE — The health authorities are still getting to the bottom of how the clusters of Covid-19 outbreaks began in recent weeks here, with the largest being the 40 cases at Tan Tock Seng Hospital (TTSH) as of Wednesday (May 5).

At a briefing held last week by the Government’s Covid-19 task force, the team was asked how the hospital cluster had started. 

In his reply, Associate Professor Kenneth Mak, the Ministry of Health’s director of medical services, said that there is no clear answer yet since investigations are still ongoing.

The process of drilling down to the index case, or the first identifiable case of a group of related communicable disease cases, is a long drawn one that could take weeks, infectious disease experts told TODAY.

Even when that is completed, they added that the findings may still be inconclusive after all avenues are exhausted, because the methods used to trace the index case are not entirely foolproof. 

The following are some burning questions surrounding the hunt for the original source of infection.

WHY IS IT CRUCIAL TO PINPOINT INDEX CASES?

An index case, or “patient zero”, is the first person known or believed to have introduced an epidemic or outbreak to a place. 

The infectious disease experts interviewed by TODAY agreed that it is important to identify the index case of an outbreak because determining the source of the infection will help the authorities in deciding what measures should be put in place to contain the transmission of the disease within the cluster and elsewhere.

Dr Vincent Pang, an assistant professor at National University of Singapore (NUS), said that identifying the infection source can help with better understanding the potential gaps in measures and protocols that may have started the cluster in a specific setting.

This is so that policies and practices can be further strengthened to prevent future outbreaks from occurring.

During the task force’s briefing on Tuesday, Assoc Prof Mak said that preliminary investigations into what led to the Covid-19 cluster at TTSH suggested that there were no specific lapses in process and protocols among hospital workers.

However, the authorities are considering hypotheses such as issues with air flow and ventilation at a particular ward in the hospital, since the infected cases had clustered around Ward 9D, he added.

Commenting on the hypotheses, Dr Pang said it is possible that there are air flow issues at the hospital.

“A technical measurement of air flow would be more appropriate to assess if air flow is indeed later determined to be one of the contributing risk factors that requires further enhancement,” he said.

The outbreak may be due to more than one risk factor and it is usually difficult to differentiate which factors greatly contributed to the transmission, he added.

“Furthermore, air flow in a healthcare setting is typically more controlled and well-established, from the building design stage, to prevent intermixing between red (hazardous) and green (non-hazardous) zones.”

Professor Paul Tambyah, president of the Asia Pacific Society of Clinical Microbiology, said that if the wrong index case is identified, some branches of the infection might be missed and the outbreak may continue to spread.

Failure to identify the right index case could also lead to a wrong understanding of how the disease is being spread.

He pointed to the example of the severe acute respiratory syndrome (Sars) outbreak at the Singapore General Hospital in 2003, which was difficult to contain initially because the index case was initially presumed to be a medical registrar at the hospital.

That index case turned out to be an elderly Chinese patient with prior illnesses and only after he was identified that investigations could be properly directed and the outbreak contained.

WHY FIRST CASE DETECTED MAY NOT BE ‘PATIENT ZERO’

Giving an update on the TTSH cluster a week ago, Assoc Prof Mak said that the nurse who was the first reported case of the outbreak “may not be the original patient that was infected, nor the cause for other patients and staff to be infected as well”.

Explaining why the first detected case in an outbreak may not necessarily be patient zero, Dr Pang said that the original patient who introduced the infection may have already recovered and is no longer shedding viral fragments. 

Hence, he or she will not be detected by the time the massive swab exercise is conducted when the first case was identified.

Dr Pang, who is also the director of the Centre for Infectious Disease Epidemiology and Research at the NUS Saw Swee Hock School of Public Health, pointed out that the index case may also be someone who is not living or working at the specific cluster setting, and therefore would not be involved in any mandatory surveillance programme conducted to sniff out cases.

Professor Leo Yee Sin, executive director of the National Centre for Infectious Diseases, said that if investigators cannot determine where or from whom the first case detected had been infected, they would have to look for other evidence to establish whether the first patient is indeed the source of an outbreak.

HOW DO INVESTIGATORS DETERMINE THE INDEX CASE?

The experts said that a combination of two methods are used to trace back to the index case of an outbreak.

The first would be the classic approach of contact tracing, which would be to take a detailed history on the onset of symptoms and use the known incubation period to determine the index case, Prof Tambyah said.

Professor Dale Fisher, a senior infectious disease consultant at the National University Hospital, said that investigators also take into consideration the places that an infected person has visited, as well as how long the person remained at the place, to trace an infected person’s close contacts.

The other method would be to use molecular epidemiology to identify the index case.  

This means looking at the gene sequencing of the virus samples to see if the samples from the cases within an outbreak are similar. 

Dr Pang said that these investigations usually involve massive exercises of active swabbing, serology screening, extraction of data, interviews and interpretations. So this would take up to a few weeks to complete.

ARE THESE INVESTIGATIONS 100% ACCURATE?

Prof Tambyah noted that in his experience being involved in a number of outbreak investigations, “luck” also plays a huge factor in how quickly an index case is identified. This is because investigations can never be entirely accurate.

“Sometimes, the index case is never identified,” he said.

Until today, for instance, the index case or animal origin of the Sars-Cov-2 virus that causes Covid-19, which first sprang from Wuhan, China, has yet to be identified. 

Agreeing, Dr Asok Kurup, an infectious disease specialist at Mount Elizabeth Hospital, said that index cases are sometimes detected incidentally.

The experts had mixed views on whether the public should be worried if the authorities are unable to determine an index case in an outbreak.

Dr Pang from NUS said that Singapore’s multi-pronged approach in detecting cases and the mass exercises to swab and to do serology testing for past infections mean that the risk of ongoing transmission at a specific setting would be minimal when all the cases test negative and there are no other cases reported from the cluster in the next 28 days.

“In addition, an infected case is likely more infectious during the first eight days of illness. As such, there would not be any public health concern even if we are unable to determine the primary case,” he added.

However, Prof Fisher noted that there have still been a handful of cases with no known sources of infection cropping up in Singapore, suggesting that “there may be something small going on in the background”.

That is why the authorities have not relaxed rules on mask wearing and physical distancing, because these measures would prevent the disease from spreading rapidly, he said.