The virus hunters: leading the way in testing and diagnostics
The importance of Hong Kong’s research into zoonotic infectious diseases and the potential of this work to contribute to the battle against SARS-CoV-2 is personified by Professor Malik Peiris (Croucher Senior Medical Research Fellowship 2005), Chair of Virology at the University of Hong Kong’s (HKU), School of Public Health.
The on-going coronavirus outbreak is the fourth occasion that this eminent clinical and public health virologist has been at the centre of what he calls a “life-changing experience”. Peiris was responsible for hospital diagnostics during the avian flu epidemic (A(H5N1)) in 1997 and the severe acute respiratory syndrome (SARS) crisis of 2003-04 when he was credited with playing a key role in the discovery that a novel coronavirus was the cause of SARS, its diagnosis and pathogenesis. In 2009, he was involved in the response to the H1N1 pandemic.
This time he was alert to the potential threat, guessing “before it was official” that this was a coronavirus and already putting strategies in place for diagnostics. “We have been closely involved since January,” said Peiris, who also served as an expert adviser to the World Health Organisation (WHO) emergency committee assessing whether to designate the coronavirus a public health emergency of international concern and co-directs the WHO H5 Reference Laboratory at HKU.
Testing and diagnosis are at the heart of the work that Peiris and his team undertake, and he works closely with Professor Leo Lit Man Poon (Croucher Senior Research Fellowship 2017), head of the Division of Public Health Laboratory Sciences, who leads on diagnostic research.
The team is now almost exclusively focused on SARS-CoV-2, with Peiris having diverted funds from other sources and projects, while awaiting the outcome of emergency government funding applications.
The 50-strong laboratory team collaborates closely with the epidemiologists led by Professors Gabriel Leung and Ben Cowling, and with a global network reflected in Peiris’s roles as an investigator in the Centers of Excellence for Influenza Research and Surveillance (CEIRS) programme under the National Institute of Allergy and Infectious Diseases (NIAID) National Institutes of Health, US, and service to many standing and ad-hoc advisory committees of WHO and the Food and Agriculture Organisation of the United Nations (FAO).
Among the foremost priorities to facilitate public health policy is reliable laboratory diagnosis.
HKU’s School of Public Health team had reverse transcription polymerase chain reaction (RT-PCR) diagnostic tests in place for SARS-CoV-2 very early and these tests were immediately in huge demand.
Once the viral genome sequence was made available by the Chinese authorities on 10 January, in theory any number of laboratories could have made a RT-PCR diagnostic test but it needed a positive control to test against and there was no virus sample from a real patient at this initial stage. So the School of Public Health team used SARS as the control. Design and validation were enabled by the close genetic relatedness to the 2003 SARS-CoV virus and aided by the use of synthetic nucleic acid technology.
The test was one of the first of two to be posted on the WHO website and details were published in a collaborative paper in January in which Peiris and colleague Dr Daniel Chu were co-authors. In addition to the information published online for laboratories, in work led by Poon, the School of Public Health has supplied test materials to many developing countries and validated their early test results.
“We have supplied the test kit to about 45 countries so far and some nations like Sri Lanka, Cambodia and Egypt made their first COVID-19 diagnosis using the kit developed here at this lab,” Peiris said.
The test has since been updated and made more specific but the original test has proved robust. Peiris explained there is some merit in having a broadly reactive-based test for the virus. Too specific primers may miss the virus if it mutates.
The team is involved in many research aspects of SARS-CoV-2. Correspondence published in the New England Journal of Medicine in February 2020 and co-authored by Peiris with researchers in Guangzhou and Zhuhai revealed the maximum SARS-CoV-2 viral load detected by PCR testing occurred as symptoms developed or slightly before, a finding that makes contact tracing and containment more difficult.
This also makes this coronavirus different from SARS where viral load peaked by the end of the first week of symptoms, which made it easier to break the chain of transmission. “We were the one of the first to warn that this is more like flu then SARS,” Peiris said.
Critically, the small sample group in the study included one asymptomatic patient who tested positive several times, over several days, but did not develop symptoms. The viral load detected in this asymptomatic patient was similar to that in the symptomatic patients, which suggested the transmission potential of asymptomatic or minimally symptomatic patients.
Another piece of important research undertaken by Peiris, Poon, and their team, and published online as correspondence in March 2020 by The Lancet, indicated that the clinical spectrum of COVID-19 can be highly heterogeneous. Examining viral RNA shedding patterns observed in patients with mild and severe symptoms, the team discovered that the mean viral load of severe cases was around 60 times higher than that of mild cases, suggesting that higher viral loads might be associated with severe clinical outcomes.
Such research has also highlighted the importance of the team’s drive to develop antibody tests for population-based testing in order to establish how common the virus is at the population level.
It is important to distinguish between the PCR test, which requires a nasal or saliva swab to test for the presence of the virus and the antibody test that requires a blood sample and tests for the antibodies produced by the patient’s immune system. Those antibodies are long-term markers of infection and will establish how many have been infected including those who have (or had) mild symptoms and those who are asymptomatic.
Peiris said this will change the whole equation because currently the severity of the virus is based on tests of those patients who come to medical attention, which represents a pre-selected subset. It is necessary to know the “size of the iceberg below this subset” but at the moment no one does, he said. Estimates of fatalities range up to two per cent but the reality could be lower, he added.
Estimates of the fatality rate for 2009 swine flu pandemic were initially reported as 10 per cent in Mexico and later as two per cent. But when Peiris did extensive antibody testing in 2009, the case fatality rate was lower by a factor of a thousand. With COVID-19, it is unlikely to be as dramatic a difference, but it is also unlikely to be the same as the currently quoted figures, he said.
“Everyone is talking about herd immunity for which it is estimated that 50-55 per cent of the population must be infected. But no one has a clue where we are. So this is why this is so important,” Peiris said, advocating large-scale population-based virology as an urgent priority.
Peiris has proposed this scale of testing in the place where the information is most needed: in Hubei Province, the first region to be hit by the pandemic. Documentation of high “herd immunity” there would allow a faster normalisation of economic activity.
Meanwhile, serological testing in the community is starting in Hong Kong, helping to keep the city at the forefront of global developments in the pressing battle against COVID-19.
Professor Malik Peiris is a clinical and public health virologist with a particular interest in emerging virus disease at the animal-human interface including influenza, coronaviruses (SARS, MERS) and others. His current research encompasses the pathogenesis, innate immune responses, transmission, ecology and epidemiology of human and animal (poultry, swine, wild birds) influenza viruses. His research has provided understanding on the emergence and pathogenesis of the 2009 pandemic H1N1 virus and on avian influenza viruses H5N1, H9N2 and H7N9. His collaborative research has provided evidence-based options for the control of these viruses in poultry and in humans. In 2003, he played a key role in the discovery that a novel coronavirus was the cause of SARS, its diagnosis and pathogenesis. Currently he is researching the recently emerged MERS coronavirus. Professor Peiris received his Croucher Senior Medical Research Fellowship in 2005.
To view Professor Malik Peiris’s Croucher profile, please click here.