On the front line of the response to COVID-19

The Peter Doherty Institute for Infection and Immunity has been at the forefront of the response to COVID-19 since January 2020 and continues to lead the way in research and policy advice.

The Doherty Institute has been at the forefront of the response to COVID-19 since January 2020 and continues to lead the way in research and policy advice. The Institute is a joint venture between the University of Melbourne and The Royal Melbourne Hospital, combining research, teaching, public health and reference laboratory services, diagnostic services and clinical care in infectious diseases and immunity.

Doherty Institute

THE CUTTING EDGE OF COVID-19 RESEARCH

COVID-19 changed the world in 2020, infecting millions and killing hundreds of thousands globally. Those who did not become ill were physically isolated, while many lost their jobs or juggled home schooling with working from kitchen tables and lounge rooms around the world.

From the moment news reports surfaced about SARS-COV-2, the virus that causes the disease COVID-19, in Wuhan, China, the Doherty Institute team swung into action to do what it was conceived and purpose-built to do – investigating infectious disease threats to human health and developing ways to treat and beat them.

It showed the spirit of the Institute’s namesake, University of Melbourne Laureate Professor Peter Doherty AC (Hon LLD 2012) who shared the 1996 Nobel Prize with Rolf Zinkernagel for their discoveries of transplantation and ‘killer’ T cell-mediated immunity, which ultimately translated into new cancer treatments.

The Doherty Institute has shown phenomenal global leadership through this challenging and uncertain time and has helped put Melbourne and indeed Australia on the map as a world leader in infectious disease preparedness and response.

Among other things, the Doherty Institute was the first lab outside of China to grow the virus, and the first to share it with public health laboratories globally in January 2020. It has modelled infection projections to help policy makers in government, and continues to work towards a possible vaccine and identify potential treatments.

Doherty Lab

LEADERSHIP THROUGH ADVERSITY

The Doherty Institute was thrust into the international spotlight when COVID-19 emerged, and its research has since contributed to global knowledge about the pandemic. Director Professor Sharon Lewin AO and her team played a big role in educating the public and dispelling myths.

Professor Lewin was integral in mobilising government and philanthropic funding while pivoting the Institute’s attention to COVID-19, and maintaining its other important work. In April 2020, she explained that 300 clinical trials had already begun around the world. Many involved existing drugs for other conditions, such as HIV and Malaria.

“We have a range of antiviral drugs and a range of drugs that modulate the immune system and they need to be tested in clinical trials,” she said. “We have two big clinical trials now happening across the country.”

“One of them is REMAP-CAP which is looking at antiviral drugs and drugs that modulate the immune system in hundreds and thousands of people in intensive care across Australia and around the world. And the other is a large clinical trial called ASCOT, led out of the Doherty Institute.”

Professor Doherty also helped to inform the public throughout the COVID-19 crisis by appearing in the media, using social media and producing a blog on the Institute’s website. In late May 2020, he said that after doing well to contain the spread, Australia was heading into unknown territory.

“At the Doherty Institute, our scientists and medical professionals who are involved in community testing, in the development of drug and vaccine strategies, and in co-ordinating with diagnosticians, researchers and physicians locally, nationally and internationally (a key information stream), are immensely grateful to our political leaders and to our fellow citizens for the respite of this lockdown period,” he wrote.

“For the immediate future: our best hope is, I think, that we can keep the incidence of infection down to ‘spot fires’, to limited ‘cells of SARS-CoV-2 terrorism’. Whatever happens, many lives will have been saved.”

Speaking to the University of Melbourne’s Pursuit, Professor Doherty agreed that trialling existing drugs would potentially mean a faster solution for the pandemic. “I think it’s very likely we’ll get to good drugs even quicker than we’ll get to a good vaccine,” he said.

GROWING AND SHARING THE VIRUS

In January 2020, Doherty Institute scientists became the first outside China to grow the 2019 novel coronavirus (COVID-19) in cell culture, and the first to share the virus with other labs around the world. They successfully grew it from a patient sample, which provided international laboratories with crucial information.

The sample had arrived at The Royal Melbourne Hospital’s Victorian Infectious Diseases Reference Laboratory (VIDRL) at the Doherty Institute.

The breakthrough allowed accurate investigation and diagnosis of the virus globally. Chinese officials had released the genome sequence, but having the real virus allowed scientists to validate and verify all test methods and compare their sensitivities and specificities. This was a game changer for diagnosis.

The Royal Melbourne Hospital’s Dr Julian Druce, who is the Virus Identification Laboratory Head at the Doherty Institute, said the virus was used as positive control material for Australia’s network of public health laboratories, and shipped to expert laboratories working closely with the World Health Organization (WHO) in Europe.

Doherty Institute Deputy Director Dr Mike Catton said possession of a virus isolate extended what could be achieved with molecular technology. It could also be used to generate an antibody test that detects the virus in non-symptomatic patients who were unaware they had it.

“An antibody test will enable us to retrospectively test suspected patients so we can gather a more accurate picture of how widespread the virus is, and consequently, among other things, the true mortality rate,” Dr Catton said. “It will also assist in the assessment of effectiveness of trial vaccines.”

COVID-19 Virus

MODELLING A RESPONSE

In February 2020, a collaboration of epidemiologists from around Australia, led by the Doherty Institute were asked by the Commonwealth Government to model the impact of COVID-19 on Australia’s healthcare system, to inform transmission reducing measures and health system preparedness.

Released in April, the modelling was based on preparedness scenarios to inform planning and actions taken to slow the spread and prepare the health system. The results were not predictions.

Led by Doherty Institute and University of Melbourne experts including Professor Jodie McVernon and Professor James McCaw (BSc (Hons) 2001, PhD 2005), the work was used by the Australian Government in its public health response to COVID-19. Their draft manuscript found that an unmitigated COVID-19 epidemic would dramatically exceed the capacity of the Australian health system, over a prolonged period.

“Overlaid social restrictions will need to be applied at some level over the course of the epidemic to ensure that systems do not become overwhelmed, and that essential health sector functions, including care of COVID-19 patients, can be maintained,” it found.

“Attention to the full pathway of clinical care is needed to ensure access to critical care.”

TRIALLING EXISTING DRUGS

Quickly finding an effective treatment for COVID-19 is paramount but comes with many challenges.

As COVID-19 is a ‘new’ disease, there are no treatments with established effectiveness. However, there are multiple treatment options, and combinations, that could be effective.

The antiviral drug remdesivir has shown to be effective in reducing the time to recovery, and is now considered the standard of care for patients in hospital with hypoxia (low oxygen levels). In addition, dexamethasone – a steroid agent – has been shown in a large overseas trial to reduce mortality of patients and is being broadly used as part of standard of care in hospitals. Also in April, Monash Biomedicine Discovery Institute (BDI) led a collaborative study with the Doherty Institute that showed an anti-parasitic drug killed SARS-COV-2 within 48 hours.

The BDI’s Dr Kylie Wagstaff led the study, in which scientists showed that the drug, Ivermectin, stopped the SARS-CoV-2 virus growing in cell culture within 48 hours. Ivermectin is an FDA-approved anti-parasitic drug that has also been shown to be effective in vitro against a broad range of viruses including HIV, Dengue, Influenza and Zika virus.

Convalescent plasma has been introduced to the AustralaSian COVID-19 Trial (ASCOT) and Randomised, Embedded, Multi-factorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) clinical trials in a bid to identify the best strategy to treat patients hospitalised with COVID-19.

As part of the immune response, people recovering from COVID-19 can develop antibodies targeting parts of the SARS-CoV-2 virus. These antibodies are contained in the liquid part of the blood, the plasma, and can be given to patients newly infected with COVID-19 via plasma transfusion, potentially resulting in more rapid control and clearance of the virus.

Led by Associate Professor Steven Tong (MBBS (Hons) 1998) a Royal Melbourne Hospital infectious diseases clinician and co-lead of clinical research at the Doherty Institute, ASCOT attracted generous philanthropic support. With its first site at The Royal Melbourne Hospital, it planned to recruit patients at more than 70 hospitals in every state and territory, plus 11 hospitals in New Zealand.

Professor Lewin said the ASCOT aimed to test whether using a combination of existing drugs could prevent patients needing a ventilator in the intensive care unit. This would ultimately save lives.

The Doherty Institute also made a significant contribution to the REMAP-CAP, another COVID-19 platform for evaluating the efficacy and safety of particular drugs in a clinical setting.

MAPPING THE IMMUNE SYSTEM RESPONSE

One of the early Doherty Institute breakthroughs that gained significant international attention was the successful mapping of the immune response from one of Australia’s first COVID-19 patients, demonstrating the body’s ability to fight the virus and recover from the infection.

Doherty Institute researchers conducted four blood tests on an otherwise healthy woman in her 40s, who presented with COVID-19 and had mild-to-moderate symptoms requiring hospital admission.

The detailed immune response report – a first for COVID-19 – was published in Nature Medicine.

The research team was able to act rapidly thanks to SETREP-ID (Sentinel Travellers and Research Preparedness for Emerging Infectious Disease), led by Royal Melbourne Hospital Infectious Diseases Physician Dr Irani Thevarajan at the Doherty Institute.

SETREP-ID is a platform that enables a broad range of biological sampling in returned travellers. “We already had ethics and protocols in place so we could rapidly start looking at the virus and immune system in great detail,” Dr Thevarajan said. “We now plan to roll out SETREP-ID as a national study.”

Working with University of Melbourne Professor Katherine Kedzierska, a Doherty Institute laboratory head and world-leading influenza immunology researcher, the team’s COVID-19 immune response work might be the secret to finding an effective vaccine.

“We showed that even though COVID-19 is caused by a new virus, in an otherwise healthy person, a robust immune response across different cell types was associated with clinical recovery, similar to what we see in influenza,” Professor Kedzierska said.

Lab work

THE EFFORT TO DEVELOP A VACCINE

A vaccine has widely been described as a silver bullet in the COVID-19 fight, but the path to its success is not without its hurdles. Normally a complex and lengthy process, Doherty Institute researchers were at the global forefront as efforts to develop a vaccine accelerated across the world.

In May 2020 they contributed to a Rapid Research Information Forum (RRIF) report on promising vaccines for COVID-19. Convened and chaired by Australia’s Chief Scientist, Dr Alan Finkel AO, it was led by the Australian Academy of Science and supported by a collaboration of participant organisations.

The forum answered pressing questions from Ministers and other key decision makers, and supported the Chief Medical Office, the Australian Health Protection Principal Committee, and the National COVID-19 Coordination Commission. The RRIF report contained the latest vaccine developments nationally and globally.

It found that technological advancements had enabled the rapid sequencing of the SARS-CoV-2 genome and provided essential groundwork for a globally effective vaccine. Another challenge was the possibility that the virus would mutate and render a vaccine ineffective.

The contributing authors were Professor Peter Doherty AC, Professor Dale Godfrey (Department of Microbiology and Immunology) and Professor Damian Purcell (BSc (Hons) 1983, PhD 1988) (Department of Microbiology and Immunology).

Despite many challenges, including the lack of any human coronavirus vaccine, Australian experts are positive a COVID-19 vaccine will be produced and possibly in our own backyard. Professor Ian Frazer AC (MD 1988), a Brisbane-based immunologist who co-created the HPV Cervical Cancer vaccine said, “It very well could be Australians who beat this thing.”

Professor Doherty agreed. “We’ve got really good science here,” he said. “We’ve got some really good people. In fact, I don’t think I’ve really appreciated how good they are until now.”

SEQUENCING GENES TO FIND ANSWER

In late May 2020, Doherty Institute researchers announced they had used whole genome sequencing to identify genetic mutations in Victorian COVID-19 cases and pinpoint clusters and transmission networks. This could also help limit the spread of the virus.

Whole genome sequencing of pathogens in real-time is an important tool in managing public health responses to infectious disease outbreaks. The team included researchers from the Doherty Institute’s public health laboratories and the Victorian Department of Health and Human Services (DHHS).

University of Melbourne’s Professor Benjamin Howden, Director of the Microbiological Diagnostic Unit Public Health Laboratory (MDU-PHL) at the Doherty Institute, said they sequenced a large number of Victoria’s cases. “We found that most of Victoria’s cases were imported with limited onward transmission,” Professor Howden said.

“Sequencing allowed us to identify large clusters from social venues, healthcare facilities and cruise ships, and, importantly, see how enforced social restrictions impacted transmission. Finally, we were able to demonstrate how the application of genomics will become critically important to rapidly identify SARS-CoV-2 transmission chains as social restrictions ease globally.”

Victoria’s Chief Health Officer and University of Melbourne alum, Professor Brett Sutton (MBBS 1993), said public health responses had to be swift, highly focused, and effective. “Working so closely with the team at Doherty Institute, who rapidly shared the sequences they found, has had a huge positive impact on Victoria’s successful response to limiting transmission of SARS-CoV-2,” he said.

WHERE TO NOW?

The COVID-19 pandemic continues to test Australia’s scientific community, political leaders, and the public. Australia’s response, led by organisations such as the Doherty Institute and other University of Melbourne experts, has been widely considered first class.

As we begin to adapt to our new normal, our world class researchers and clinicians continue to work on possible treatments, a vaccine and other ways to help people whose lives were affected by the pandemic.

Keep up to date with the work of the Doherty Institute by visiting the website or tuning into Life Beyond Coronavirus: The Expert View.