Looking to 2022: What lies ahead in the COVID-19 pandemic
| By Professor Paul Tambyah and Assistant Professor Lionel Lum |
COVID-19, the third coronavirus outbreak in the past 2 decades after SARS and MERS, has severely tested the global healthcare infrastructure over the past two years and Singapore has not been an exception. We have had waves of infection beginning with imported cases leading to community transmissions and occasionally clusters in health institutions and long-term care facilities and a huge outbreak in our migrant worker dormitories in 2020.
Intensive research by many global institutions including NUS have led to constantly changing paradigms in clinical management and public health policies, as we dealt with a new way of life with social restrictions, digital interactions and unending cycles of evolving safe management measures.
Tight contact tracing, isolation and quarantine were widely used in the “zero covid era” as Singapore and other countries tried to eliminate the virus. Once that proved impossible, the focus was on mitigating the effects of the pandemic by ensuring the smooth functioning of the healthcare system. As with any infectious disease, infection control, vaccines and therapeutics took centerstage.
While oral antiviral therapies such as Paxlovid and Molnupiravir have been licensed for early outpatient use, their real world efficacy has not been proven yet. For outpatient drugs like these, the challenge, is also to ensure that diagnosis is made early in the outpatient setting so they can be used appropriately. Several NUS groups from the NUS Yong Loo Lin School of Medicine (NUS Medicine), NUS Saw Swee Hock School of Public Health and our partners have made great strides in the development and evaluation of COVID-19 test kits.
We have also conducted a large scale prophylaxis study using repurposed agents which waits for reproduction in other settings. This study led by Associate Professor Raymond Seet led to nationwide distribution of a topical povidone iodine product. In the coming year, we can see a more thorough evaluation of these and other antiviral agents for both early treatment and possibly prophylaxis.
One piece of good news is that thanks to the release of patents to low and middle income countries, both Paxlovid and Molnupiravir are more likely to benefit more people globally especially where logistical limitations prevent the early use of intravenous monoclonal antibodies. While these antibodies have the potential for prophylactic and therapeutic use their cost and complexity effectively currently limit their widespread use to higher income countries.
The next steps in vaccine development and distribution
The prevention of COVID-19 has largely been centered around the use of COVID-19 vaccines in addition to infection control. Singapore is one of the most highly vaccinated nations with 89 per cent of the total population fully vaccinated predominantly with the mRNA vaccines or the inactivated viral vaccines. There is currently a further drive to extend vaccinations to children and to roll out boosters for possibly enhanced protection.
However, vaccine inequality in resource poor countries remains a gap which needs to be closed. Next generation vaccine candidates such as protein-based vaccines which do not need a cold chain may make a breakthrough in resource-limited settings. The newer vaccines in addition may be more effective in preventing transmission or disease instead of just reducing the severity of disease. Needle-free vaccines, in the form of nasal spray, oral tablets or patches are in development and again, many NUS multidisciplinary programs are exploring these alternative vaccine approaches.
With emerging variants exhibiting immune escape and rapidly waning immunity from current mRNA and other licensed vaccines, developing multivalent vaccines which protect against multiple variants or ideally using vaccines that prevent transmission of the virus like most other licensed vaccines may contribute significantly to the management of COVID-19 in the future.
The end of the pandemic?
New and more effective vaccines will remain important even if the virus becomes simply the fifth seasonal coronavirus. Older institutionalized individuals are still vulnerable to seasonal coronaviruses and more targeted routine vaccination programs may be rolled out once the World Health Organisation declares this current pandemic over. That declaration that we are all waiting for would depend a great deal on a better understanding of how the virus interacts with humans.
Coronaviruses in general and SARS CoV2 in particular do not appear to mutate as fast as influenza viruses probably due to a viral checking mechanism which prevents mutation causing errors in viral replication. However there are still many factors that need to be taken into consideration about our immunity to the virus from vaccination, disease and possibly other viruses.
All of these have implications as to whether we will need annual COVID-19 vaccinations similar to what is done with influenza or whether a single vaccination series would be adequate as with measles or the bacterial pneumococcal vaccine.
The next pandemic on the horizon
While this pandemic will most certainly end either this year or the next, there is every likelihood that another will soon arise, most likely influenza which has lain dormant for a while.
The question arises about how we will respond – will there be more “circuit breaker” style lockdowns with the first few cases of the next pandemic virus in some country nearby in a bid to flatten the epidemiology curve and to safeguard our healthcare resources and capacity? We have learnt from experience this drastic measure may be detrimental to the economy and morale of people and may also lead to unintended effects on mental health and other medical care.
Rather we will most likely shift to more sustainable and balanced public health approach. This will include a combination of non-pharmaceutical interventions including mask wearing, isolation and quarantine especially in selected higher risk settings such as near the ports and airport, healthcare or learning institutions or mass gatherings, as well as the rapid deployment of rapid diagnostics, vaccines and therapeutics.
These interventions will all take time and the temptation will remain to lockdown hard and fast. Governments will not want to be seen to be taking the next pandemic virus lightly and it will be difficult to come up with a calibrated approach in the face of another novel threat.
Transparency and international data sharing will be critical. Social science thought leaders from NUS have contributed to this discussion but there are few answers readily available.
The open questions
Despite the explosion of knowledge in COVID-19, many questions remain unanswered. It is still not clear why children do not get severe disease; are there other measures of immune protection besides antibody titres that may determine acquisition and the clinical course of COVID-19?
The sequelae of COVID-19 such as long COVID and organizing pneumonia – are also not well characterized. Are these merely the tip of an iceberg of a post-infective inflammatory process triggered by COVID-19?
The mode of transmission of COVID-19 has been described to range from close contact to aerosol routes but the circumstances surrounding the different transmission modes needs redefinition – this has important infection control implications.
Further studies on immunological responses and biology of the virus will be paramount in delineating our understanding in these aspects. The NUS Medicine Infectious Diseases Translational Research Programme brings together clinicians and scientists from across the school of medicine to try to answer these and other pressing questions.
While there are many uncertainties about this virus and the next pandemic, we know for certain, that science has advanced with positive changes such as better vaccine options, better clinical trial networks including one focusing on Asia and based in NUS to evaluate the different treatment options, and more critical evaluation of public health measures.
These will remain crucial in controlling this pandemic and in responding to the next one. Despite the significant human cost and all the negative discourse surrounding this pandemic, hopefully the world is armed with a new level of preparedness and resilience to face the virus when (not if) it comes.
About the authors
Dr Paul Ananth Tambyah is Professor of Medicine and Clinical Programme Lead for the Infectious Diseases Translational Research Programme at the NUS Yong Loo Lin School of Medicine. He is also a Senior Consultant at the Division of Infectious Diseases at the National University Hospital. He is President of the Asia Pacific Society of Clinical Microbiology and Infection, and also President of the International Society of Infectious Diseases.
Dr Lionel Lum is Assistant Professor and Clinical Tutor at the NUS Yong Loo Lin School of Medicine. He is also a Consultant at the Division of Infectious Diseases at the National University Hospital.
Looking to 2022 is a series of commentaries on what readers can expect in the new year. This is the fifth instalment of the series.
Click here to read Professor Tommy Koh's commentary on three upcoming anniversaries that will be key to international geopolitics.
Click here to read Professor Danny Quah's article on how societies can build back stronger from the pandemic.
Click here to read Professor Freddy Boey's views on opportunities for start-ups in the New Normal.
Click here to read Associate Professor Tan Ern Ser's commentary on enhancing retirement financial adequacy for our seniors.