Clinical management: lessons from SARS

15 April 2020

Hong Kong government medical adviser and respiratory disease expert Dr David Shu Cheong Hui describes the city’s approach to clinical management of COVID-19 and how it has learnt from past experience with SARS

On 31 December 2019, unusual cases of pneumonia in Wuhan, China, were reported to the World Health Organisation (WHO). The outbreak was associated with a seafood market where game meat was also sold.

A novel coronavirus, later named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was found to be the cause of this outbreak on 7 January 2020. There is 79.5% similarity of SARS-CoV-2 in genetic sequence to SARS-CoV and 96% similarity at the whole genome level to a bat coronavirus, as found by a recent study carried out by a Wuhan and Beijing joint research team and published in Nature.

Rapid characterisation, asymptomatic infections

The outbreak was quickly spread throughout China by travellers moving around nationally and to other countries. It was declared a Public Health Emergency of International Concern on 30 January 2020 and WHO announced a name on 11 February 2020 for the new coronavirus disease: COVID-19. On 11 March 2020, WHO announced the extent and evolution of the global outbreak of COVID-19 had reached a pandemic.

As a China-based study on the clinical characteristics of COVID-19 showed, and that I was involved in, common symptoms of COVID-19 include fever (43.8 per cent on admission and increased to 88.7 per cent during hospitalisation), cough (67.8 per cent), while diarrhoea is uncommon (3.8 per cent). The median incubation period is four days (interquartile range, two to seven). An article on our findings was published in the New England Journal of Medicine in February 2020.

The absence of fever in a high proportion of patients makes it easy to miss these cases in the community in the early stage of infection. However, there is evidence that patients in the pre-symptomatic stage and those with mild disease may transmit infection to others.

Viral kinetic studies have shown that the viral load peaks on day 2-3 of the patient’s illness, and this explains the high potential of SARS-CoV-2 in causing community transmission among close contacts. In contrast, the viral load of SARS-CoV peaked on day 10 during the clinical course, leading to hospital transmission infecting many healthcare workers in 2003.

Hospital readiness, learning from the past

The clinical experience in managing the outbreak of SARS in 2003 in Hong Kong has facilitated the city’s management of COVID-19 in 2020. Since 2005, double-door negative pressure isolation rooms to prevent room-to-room cross-contamination from airborne diseases have been installed in every acute public hospital and there are currently 1,400 beds in negative pressure isolation rooms.

In addition to a much safer ward environment, healthcare workers are familiar with infection control and prevention measures, wearing surgical masks in low-risk areas and upgraded to airborne precaution with N95 masks, protective gowns, eye shields and gloves when managing high-risk patients in the isolation rooms.

By the third week of March 2020, after two months of handling cases and over 300 hospitalisations, no nosocomial transmission of COVID-19 had occurred in Hong Kong.

Pathway to treatment, international clinical trial

Coronavirus contains a protease enzyme, which has become a target of therapeutics. A retrospective study of patients with SARS in Hong Kong, which appeared in the Hong Kong Medical Journal, has shown that a combination of protease inhibitors (lopinavir/ritonavir) and ribavirin was more effective in reducing the death rate [2.3 (0-6.8) per cent versus 15.6 (9.8-22.8) per cent] and intubation rate [0% vs 11.0 (7.7-15.3) per cent] versus a historical control group on ribavirin alone (n=634).

Another study by a Hong Kong-Beijing team has shown that lopinavir/ritonavir and interferon (IFN)-β1b were more effective in reducing viral loads and mortality in marmosets infected with MERS-CoV.

Based on the experience in managing SARS and the scientific data on treatment of marmosets infected with MERS-CoV, a combination of protease inhibitors, ribavirin +- beta interferon has become the local standard of care for patients with pneumonia due to SARS-CoV-2.

More recently, a US study in mice infected with MERS-CoV, published in Nature Communications, has shown that remdesivir (a RNA polymerase inhibitor) was more effective than protease inhibitors and beta interferon in reducing viral loads and lung damage. On 11 March 2020, three Hong Kong hospitals (Prince of Wales, Princess Margaret and Queen Mary) joined a multi-country, multi-centre clinical trial using a new drug, Remdesivir, for treatment of COVID-19.

Containing the second wave, renewed vigilance

Containment measures have been carried out effectively in Hong Kong since January 2020 to limit the spread of COVID-19 in the community. These include a) early isolation of suspected and confirmed cases; b) quarantine of close contacts and Hong Kong citizens who have returned from high risk areas (for example, the Diamond Princess cruise and Wuhan) for 14 days; c) social distancing measures (for example, cancellation of events involving mass gatherings, school closures, and working from home); d) public service promotions on maintaining good personal hygiene (for example, the wearing of a surgical mask on public transport/in crowded areas, and hand hygiene); and e) enhanced laboratory surveillance in testing in-patients and out-patients with febrile respiratory illness for SARS-CoV-2.

However, the return in mid-March of a large number of Hong Kong citizens from Europe and North America, where major outbreaks of COVID-19 have been occurring, has now posed a great challenge to the healthcare system in controlling the spread of the disease in the city.

A significant number of cases have been confirmed among the returnees recently and there are clusters of local transmission emerging without clear contact sources. Some of the confirmed cases have been linked to social gatherings in pubs and wedding dinners, and these high-risk activities must be avoided amid the city’s battle with the COVID-19 pandemic.

Apart from maintaining heightened vigilance and strict personal hygiene, social distancing measures are essential to reduce the risk of widespread and sustained community outbreaks, which may overload the public hospital isolation room facilities and compromise other medical services.

Concerted effort by the general public in complying with the containment measures during this “second wave” is urgently needed to prevent a major outbreak of COVID-19 in Hong Kong.

Dr David Shu Cheong Hui is Stanley Ho Professor of Respiratory Medicine and Chairman of the Department of Medicine & Therapeutics, Chinese University of Hong Kong. He is Director of the Stanley Ho Centre for Emerging Infectious Diseases and Associate Director (Clinical Liaison), both at the Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong. He was heavily involved in the clinical management of patients with SARS at the Prince of Wales Hospital during the major outbreak in Hong Kong in 2003. He has subsequently served as a regular World Health Organisation (WHO) adviser on the clinical management of severe acute respiratory infections.