The epidemiologists’ quest: tracking and halting transmission of COVID-19

11 April 2020

University of Hong Kong epidemiologists Professors Gabriel Leung and Ben Cowling discuss their leading research contributions to local, national, and global public health policy and the world’s “new normal” of pandemic containment and mitigation

Political leaders across the world are taking unprecedented action in the war against COVID-19. Science-based policy has become their new mantra and Hong Kong epidemiologists have come to the fore in advising them, and the general public, on the next moves to slow and eventually defeat the pandemic.

Among the most prominent of these internationally renowned experts is Professor Gabriel Leung, the Dean of the University of Hong Kong (HKU) Faculty of Medicine and Chair Professor of Health Medicine, informed by his prolific research and the strength of the faculty he leads.

He works closely with two colleagues that he recruited to HKU in the wake of SARS. Professor Ben Cowling (Croucher Senior Research Fellowship 2015) and Professor Joseph Wu Tsz Kei have been responsible for much of the data analysis and modelling and on the spread of COVID-19 done by the School of Public Health at HKU.

Their expertise focuses on how infectious diseases are transmitted from individual to individual, how epidemics develop in a population, how fast they spread, and how effective are the public health measures that could control them. That vital information is relayed to local, national, and international policymakers, with Leung an adviser on COVID-19 to the Hong Kong and Mainland China governments, and all three working closely with the World Health Organisation (WHO), among other agencies.

Leung has conveyed the message locally and globally that we are in for a long journey in the current pandemic. “This is the new normal,” he cautioned in an interview for the Croucher Foundation. “There is not going to be a definitive resolution until most people have natural immunity through past exposure, or conferred by vaccination.” Although HKU has joined the global efforts to develop a vaccine and the first human trials have begun, he does not expect one to be available for at least a year.

Yet he is under no illusions that allowing the disease to spread unchecked, to the point that so-called herd immunity has been achieved among the majority of the population, would involve a humanitarian catastrophe, particularly for the elderly and poor communities that lack access to adequate healthcare.

Instead, he has proposed a framework for interventions, such as lockdowns and social distancing, to manage the disease.

“The ultimate objective must be to bring the epidemic down to a slow burn so as to buy time for the world’s population to acquire, one way or another, immunity to COVID-19,” he recently wrote in a New York Times article. Yet draconian lockdowns could not be the long-term answer, given the economic consequences, and social resistance that would emerge.

Leung thus put forward a formal framework for how governments could balance the tensions between limiting the transmission of the disease and continuing with normal life. This involves more accurately monitoring the pandemic in its successive waves, and using that evidence to tune the interventions in what he describes as a cycle of “suppress and lift”. This echoed research, published on 8 April 2020 in The Lancet, analysing cases in China. The study by Wu and Leung showed the potential effects of relaxing containment measures after the first wave of infection, in anticipation of a possible second wave – highly relevant as governments across the world struggle to balance the need to contain the disease and resume normal economic activity.

The framework builds on Cowling and Leung’s research that determines real-time transmission rates (Rt), rather than reported cases – the latter inconsistent across countries due to different testing policies and time-lags for incubation and time when people may eventually be tested. The Rt, along with estimates of the case fatality risk (CFR), are vital for the “nowcasting” needed to pinpoint the pandemic’s progress.

HKU’s School of Public Health has provided a dashboard for real-time Rt for Hong Kong since early February, with the epidemic curve corrected by statistical methods to reduce the time lag between the onset of infection symptoms and the official reporting of new cases. The team plans to enhance the estimates by incorporating location-based data from the Octopus payment card used widely in Hong Kong to reveal, anonymously, how people are mixing, from which it can be inferred how likely they may pass on the virus.

Leung, Cowling and Wu began working on COVID-19 in earnest towards the end of January 2020, when they and other colleagues were invited by the Chinese Centre for Disease Control and Prevention (CDC) to travel to Beijing to assist in the analysis of data from the Wuhan outbreak.

They investigated the first 425 confirmed cases to determine the epidemiologic characteristics of the new coronavirus, later called SARS-CoV-2. The resulting collaborative paper, published in the New England Journal of Medicine on 29 January 2020, established its transmission dynamics for the first time and affirmed the evidence of human-to-human transmission. From this, they recommended preventive measures to limit the spread of the disease, including the lockdown of Wuhan adopted by local policy leaders.

The three experts have explained the key factors for predicting and tracking the spread of an infectious disease. These include the basic reproductive number (R0 at time zero and pronounced R-nought) and the generation time, reflecting the time between subsequent infections in chains of transmission. This indicates how many other individuals each infected person infects on average, and the average time or interval it takes for these transmissions to occur. The effective reproductive number at time t (Rt ) represents the average number of secondary cases per one case in a population over time – the real-time transmissibility – which may change for reasons such as immunity after infection and the reduction in transmission because of effective control measures and behavioural changes.

“Our initial study was really important because we estimated the R0 in Wuhan to be 2.2. That was done on Joe’s (Wu’s) laptop on the night of 23/24 January,” Cowling said. The team estimated the average generation time as 7.5 days. This corresponded to a doubling in the number of infected people every week. “The results were alarming but we weren’t sure at that point how much it would spread around the world,” Cowling said.

At the time of the data analysis in Beijing, there were some 400 cases in Wuhan that had caused acute pneumonia but the team didn’t yet know how many total infections those cases corresponded to. “It took us to mid-late February to get a handle on that,” Cowling said. It is now thought the 400 cases corresponded to perhaps 4,000 or more total infections, although there is still uncertainty based on the unknown numbers of individuals who are asymptomatic, which Leung said needed to be investigated through serological antibody tests.

After the Beijing visit, the School of Public Health’s large team of epidemiologists switched their attention from influenza research to coronavirus and most on-going projects were suspended. Their COVID-19 team, consisting of nine academic staff, three postdocs and 21 technical staff and students, work closely with the laboratory-based team at the School of Public Health, which consists of dozens of staff. “It’s a massive effort,” Cowling said.

The growth rate of the COVID-19 epidemic, calculated from the December data from Wuhan, has proved to be largely consistent with what has been observed elsewhere, though in Malaysia, Indonesia and Thailand, it did not grow as fast as in Europe, suggesting some variation in transmission by location, perhaps influenced by weather.

The early data allowed the forecasting of the spread of the virus to be undertaken more accurately and for governments beyond the Mainland, such as Hong Kong, to take appropriate containment and mitigation measures.

Containment has different components designed to stop the exponential transmission of the virus, the first being a “case-based approach” that requires intensive testing, tracing of contacts, and isolation. The key is to start early and to be aggressive with testing and tracing. The second component reduces physical contact in the community by social or physical distancing measures, such as requiring individuals to stay at home as much as possible.

This necessitates public support or compliance. But, despite early success in containment in Hong Kong and Singapore, Cowling said it is too early to determine if the measures have worked or not, and which component is more effective. Steady increases in case numbers in Singapore are now a cause for concern.

Mitigation has a different objective. It assumes that preventing an epidemic is impossible but tries to slow it down to reduce the impact on individuals and the pressures on health systems to cope within their capacities.

“We know lots of people will get very ill but we don’t want them all to be ill at the same time because that will overwhelm the healthcare system,” Cowling said, adding that the public health response to SARS-CoV-2 in terms of containment and mitigation in many Western countries has been unprecedented.

Cowling recently participated in a major WHO review of all potential interventions and public health measures available to governments in the event of a pandemic. There were 20 different measures on the list of government actions, he said. But a so-called “lockdown” was not included as an option because it was generally considered to be too economically disruptive.

Lockdowns in countries such as Italy and Spain have been introduced much later in the epidemic cycle as a containment measure to reduce transmissions. This, Cowling said, was highly unusual. More commonly, countries focused on containment in the early stages, as the Hong Kong Special Administrative Region also did, and then switched to mitigation measures later if they failed to prevent an epidemic.

For COVID-19, it has been the other way around in many countries, due to the gravity of the pandemic.

Leung has explained how advanced epidemiological methods, using real-time analyses to determine the Rt and case-fatality risk in different contexts can be used to inform a “suppress and lift” policy approach adjusted to the choices, priorities, and capacities in different societies.

He cited China as an example. The country may experience a second wave as economic activity resumes and from imported cases among travellers returning from other infected areas. “With its testing and tracing strategy, even if there is a second wave, it can be a controlled one, and the magnitude smaller,” he said.

As such, Leung appears to see no choice but to remain positive. “Keep calm, stay sane, and carry on,” he said.

Professor Benjamin Cowling joined the School of Public Health (SPH) at HKU in 2004. Prior to moving to Hong Kong, he graduated with a PhD in medical statistics at the University of Warwick (UK) in 2003, and spent a year as a postdoc at Imperial College London (UK). Professor Cowling has been the Head of the Division of Epidemiology and Biostatistics since 2013. He is responsible for teaching the introductory module in epidemiology on the MPH curriculum, and is the chairman of the Departmental Research Postgraduate Committee. He is a co-director of the WHO Collaborating Centre for Infectious Disease Epidemiology and Control at HKU SPH. Professor Cowling received his Croucher Senior Research Fellowship in 2015.

To view Professor Benjamin Cowling’s Croucher profile, please click here.