Issue 3 • 2021

COVID-19 and the role of Science and Leadership: Reflections from 2020 and looking to the future

Professor Sharon Lewin AO is an infectious diseases physician and scientist who is internationally renowned for her research into all aspects of HIV disease and pathogenesis. She is the inaugural director of the Doherty Institute for Infection and Immunity; Melbourne Laureate Professor at the University of Melbourne; consultant physician at the Alfred Hospital and Royal Melbourne Hospital; and an Australian National Health and Medical Research Council (NHMRC) Practitioner Fellow.
At the recent RACP Congress 2021 in Melbourne Professor Lewin delivered the Priscilla Kincaid-Smith Oration. She commenced the oration from a personal perspective, highlighting the work of Priscilla Kincaid-Smith and the support of her husband in a time when support was not always forthcoming to women trying to forge careers. This support was also very important in her own career as she reflected on what she had learnt through her work in HIV at the Doherty Institute and the key learnings from 2020 and the future. Straight off the bat, she noted that “we all sort of think the future is grim, post COVID-19, but I strongly believe there is a silver lining”.
After a brief recap of her early career, she dived headfirst into the HIV epidemic, with the iconic grim reaper image representing the future people with HIV faced from the 1980s through to the mid 1990s. She contrasted this with the pandemic of 2021 and the very different campaigns focused on treat early, test more, stay safe.
Professor Lewin spoke of her interest in HIV, and how it stemmed from an early trip to Kenya in 1989 where she felt the “reality of HIV that was emerging as a major global problem across Africa”. She spent two very formative years in New York City (NYC) where she worked with Time Magazine Man of the Year, Dr David Ho. Dr Ho had discovered the secret to the treatment of HIV, “which was to use a combination of anti-viral therapy in one go and this led to the major changes in health outcomes which people experienced”. It was during this period that her lifelong interest in finding a cure for HIV began.
The discovery of the latent form of HIV became her focus for the next 20 years and the NYC experience provided her with an “international network of collaborators and mentors, which not only inspired me then but inspires me now and have made a very big difference” to her research career. She encouraged young research students to take such opportunities away from the more comfortable environment of Australia, find the best place possible and meet the important leaders in their field.
Professor Lewin explored the significant role of partnerships and advocacy and how important it is, as not only clinicians but also as researchers, to deliver an impact from what they do. “We can’t do this work alone in hospitals or in ivory towers, we need to work with the people that really are affected by the diseases we work on, and we need to engage with clinicians and leaders because that’s where we get the biggest impact.”
It is vital to not only deliver the science, but deliver it to communities, and really change people’s lives beyond high income countries. “We must have these same sorts of principles as we approach COVID-19.” While HIV was the pandemic of Professor Lewin's time, and still remains a major challenge, she reflected how extraordinary it has been to look at what’s happened in controlling infectious diseases over subsequent decades, not only HIV, but also emerging and re-emerging infectious diseases and their causes, including inequity.
Speaking of her time at the Doherty Institute, Professor Lewin reflected on the early challenges in assembling a team that was ideally placed to be able to respond to COVID. She proudly noted that the Doherty Institute is one of the few institutes that brings together research, education and public health. “Public health can’t just exist as a government laboratory, underfunded, churning through diagnostic tests. It needs to be in an environment where you can capitalise on those discoveries.” She spoke of how the new COVID virus was difficult to grow and why they needed to grow the virus in order to establish new diagnostics, vaccines and therapeutics. Using previous decades of experience, they were able to isolate the virus, and because they knew of the high demand, they chose to share it globally. It was this early response that had a huge impact on managing the virus, not only in Australia, but in various parts of the world.
About 50 per cent of the 700 people working in the institute are working on COVID-19. This work includes early isolation of the virus, developing models to inform government response, and characterising the immune response to COVID-19. Speaking of the pre-approved protocols in place for studying people with infectious diseases, Professor Lewin said that this preparedness meant that they had been able to collect samples from patients presenting with COVID-19 as early as 13 January 2020. This shows that being prepared made a very big difference, not just for research but for all information used to inform government decisions. She was also pleased to note that the institute is currently leading the largest clinical trial of interventions for COVID-19, the ASCOT trial, which is proving to be very interesting. Their focus is on developing a range of vaccine candidates and developing antibodies for therapeutics.
Identifying internal communication as a key response meant that everyone who was receiving information from different pathways was able to share knowledge. Using daily meetings for the first six months ensured that everyone had access to all the information, and steps were also taken to communicate information to the public. The sharing of information allowed them to have a great many spokespeople who could speak on a range of things, from modelling, virology and vaccinology to clinical outcomes for public health.
What were some of the key learnings for 2020? “First of all, we saw the real power of genomics in infectious diseases was revealed with COVID-19. We learned that by sequencing every single isolate in Australia, we could very carefully map outbreaks across the country.” This was very important in the second outbreak in Melbourne. They were able to identify new strains and in the second wave they were also able to identify a mutation in that isolate which allowed infection in mice. Though a problematic issue, changing which animals it can infect, was also enormously helpful in developing an animal model. Professor Lewin spoke of the need for more countries to be able to do the sequencing.
The ability to make vaccines with lightning speed and now being able to compare them to previous vaccines is astonishing. Professor Lewin noted that eight vaccines were currently licensed and spoke of the timeline for the Moderna vaccine and how the lessons learned in the stabilising of spike proteins for the MERs vaccine allowed a good immune response. As a result of that, they used the same approach for COVID-19. From the publication of the sequence for COVID-19, even without the isolate on 10 January, to phase one studies for the Moderna vaccine was only six weeks. This didn’t just happen, but was built on prior thinking. Professor Lewin pointed to the work of the Coalition for Epidemic Preparedness Innovations (CEPI) in funding platform technologies, particularly vaccines, which could be rapidly adapted for a new infectious disease.
Looking at advances in COVID-19 therapeutics, the news was less rosy with advances being much slower than was hoped. There are currently only three interventions that have shown success. This is still good, but despite over 50,000 clinical trials being registered, without having a direct acting antiviral drug this enormous effort suggests improvements need to be made in preparedness in this arena for future pandemics.
Professor Lewin spoke about her collaboration with groups at the Peter MacCallum Cancer Centre which focused on novel antiviral approaches that aren’t small molecules and take advantage of advances in gene technologies. She spoke of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), or gene editing of DNA, which is used for genetic diseases, and how the same approach could be used to target RNA using a different type of delivery system, Cas13. They are looking at how they could use this delivery system as a strategy for an antiviral drug as all that is needed is a sequence of the virus, exactly the same as for the Moderna mRNA vaccines. It shows promise with the inhibition of viral replication, using the different guide RNAs to edit the SARS COVID2 virus rather than using an antiviral drug.
Professor Lewin also spoke of the leadership, and the impact of an elimination strategy over a mitigation strategy. This involved comparisons of the economic impact of the two strategies and data showing that the elimination strategy had proved more effective on the impact of the virus. She also noted with pleasure that women led countries also seemed to have fared better in the handling of the response, and that the power of community and the stories that emerged made a difference to how they responded to the challenges. What does the future hold? Avoiding the usual topics, Professor Lewin noted that faith in science, at least in Australia, is high, and the benefits for both government and communities of investing in science and partnerships are clearer, while new technologies will have benefits for other infectious diseases. The impact globally can be envisaged, both resource and knowledge gaps are now better understood, and the way we work, in terms of flexibility, will have an impact on women in the workforce.
The transformational legacy of the 1917 pandemic was the establishment of the Commonwealth Serum Laboratories and we must now look to see what the legacy of COVID-19 will be. “We certainly don’t want to go back to business as usual. We need to be far better prepared, and Australia needs to play a very major role in the region and is certainly something that needs a lot of debate and discussion.” Despite the fragmentation across state lines, Australia’s response was excellent, but can still be better. “We need research networks in place in peace time to mobilise in war time and clinical trials.” Professor Lewin also noted that clinical trials, diagnostic evaluation and data were fragmented and in competition across the country, and this needs to change. This also highlighted the gaps in core capabilities needed to rapidly test and manufacture drugs and vaccines. She also noted that Australia’s role as a global citizen has been questioned during the pandemic and that we really need to do better.
What is clear, Professor Lewin said, is that global partnerships will need massive transformation. “This was made abundantly clear when the first COVID-19 cases emerged.” The public release of genomics was delayed, and precious time was lost. Better detection and alert responses and true trusting partnerships are urgently needed. The images from India highlight the challenges of equity and one must ask, could this have been prevented? Despite the various agencies, no one agency had a system in place to manage the scale of this pandemic. The major challenges we are now seeing lie in the manufacture and supply of vaccines and technology transfer, as well as access to basic medical equipment. The lessons learned show that we do need massive global change. Professor Lewin brought the session to a close with this reminder, “no one is safe until everyone is safe from COVID”. She also paid her respects to all the frontline health workers and College members for their effort, work and commitment during the pandemic.
© 2021 The Royal Australasian College of Physicians