The COVID-19 pandemic not only threatens our physical health, but it also has a profound impact on our lives as we know it, jeopardising our families and communities. our mental health and wellbeing, our social connections and our economy. It has put our health systems under enormous strain and worsened health and social inequalities worldwide. As the UN Secretary General Antonio Guterres has warned, “the whole of humanity” is in danger. This necessitates a thorough documentation of the nature and scope of all the short and long term consequences of this unprecedented health crisis. Isabelle Bonne, Senior Research Fellow, Head of the Electron Microscopy Laboratory and Angeline Rouers, Research Fellow, Singapore Immunology Network, A*STAR present an overview of the current COVID-19 situation in Singapore and beyond.
French scientists in Singapore are fully engaged in the fight against Covid-19, which prompted the Embassy of France in Singapore to create a scientific committee comprising such experts to coordinate the efforts. The scientific committee meets regularly to share the latest updates on the repercussions of the Covid-19 pandemic in Singapore and the measures taken to protect the population.
Despite the initial quick and efficient response by the Singapore government during the first cases of Covid-19 in the early months of 2020, it is a different story now for Singapore. As of 20 May, a total of 29,364 cases and 22 deaths have been reported. The “circuit breaker” introduced on 7 April 2020 was initially slated to end on 4 May but which has since been extended to 1 June. The aim is to bring down the number of infections in the community (excluding the cases in the foreign worker dormitories) to below 10 daily. The development of a vaccine would be a game changer and scientists over the world over are rushing to push out one. However, it would be realistic to say that this may not happen before one year at least. Until then, it is crucial to slow down the rate of transmission or the R0 (reproduction rate). One method is to employ diagnostic tests to identify and isolate infected subjects as quickly as possible. Such tests would also allow a better understanding of the disease to achieve better outcomes for patients. A large part of the research focuses on the treatment protocols for patients, with several clinical trials already ongoing or about to be put in place soon.
This urgency of the situation has diverted the scientists’ focus away from their current projects to participate in the efforts to fight COVID-19. To support this initiative, two new calls for grants have been recently offered by Singaporean agencies, one of which is the Agency for Science, Technology and Research (A*STAR) for the therapeutic development. This call is opened until 25 May.
Diagnostic and serological tests: two different tests
The vast majority of tests carried out to detect the presence of SARS-CoV-2 use the RT-PCR (Reverse Transcription-Polymerase Chain Reaction) test. This test detects the genetic material of the virus, by the amplification of its RNA strand, obtained from patient samples.
Now thanks to the joint efforts of A*STAR and Tan Tock Seng Hospital (TTSH), a RT-PCR diagnostic test called the Fortitude Kit 2.0 with a high degree of precision was rapidly developed in Singapore.
Other companies like Sensing Self also developed a pre-test to screen the population. This test is produces rapid results (10 to 30 minutes) and its reliability (92%) makes it suitable for mass screening. It will be available for sale to laboratories and research entities.
Despite the availability of diagnostic tests, the research continues to find alternative tests that are quicker and easier to use. Point-of-care testing is of high interest and is currently under development at the Singapore Immunology Network (SIgN, A*STAR) headed by Professors Lisa Ng and Laurent Renia. SIgN is also collaborating with hospitals in Singapore to obtain blood samples from COVID-19 patients. Th immune response of these patients will be investigated to identify the biomarkers that differentiate the more severe form of the disease from the less severe. This might eventually translate into more targeted care for patients. Professors Vincent Chow and Paul MacAry from the NUS Yong Loo Lin School of Medicine are also conducting their own research to identify the key cells and molecules that allow certain patients to fight off this infection. The vital information gleaned could be used in vaccine development or incorporated into new tests kits to diagnose and manage infected patients.
The second type of tests – serological tests – can detect antibodies to determine if someone has been exposed to the virus. Given the high transmissibility of the virus when even asymptomatic patients are contagious, the serological test is important and will be widely deployed in Singapore to identify such cases in an effect to stem the pandemic.
Several serological tests are under development in Singapore (as well as in Europe, China and the United States). In fact, the teams of Professor Wang Linfa and A/Prof Danielle Anderson from Duke-NUS Medical School developed two tests which have been available on the Singapore market since 1 March. The first test employs “viral neutralisation” with a response time of three to five days and is very reliable. The second test with a sensitivity of around 90% returns a result in few hours. Notably, serological tests have been carried out in contact tracing efforts from February and provide an estimate of the time when the person was infected.
Another player on the market is Biolidics, a Singapore-based company, which produced a fast serological test kit to detect the IgG/IgM antibodies against SARS-CoV-2. After obtaining an approval from Singapore’s Health Sciences Authority and the authorisation for sale in the European Union, Biolidics went on to get the nod on 20 April from the Food and Drug Administration (FDA) to commercialise their kit in the United States.
The need to find an appropriate therapy as soon as possible
SARS-CoV-2 infection can be roughly divided into three stages: an asymptomatic incubation period with or without a detectable virus; a non-severe symptomatic period with the presence of virus; and a severe respiratory symptomatic stage with a high viral load.
When a patient gets to the stage where severe symptoms are experienced, the viral load falls to almost zero. At this point, retroviral drugs are no longer useful. This is because the immune system goes into overdrive resulting in a cytokine storm. It is therefore necessary to define precisely the best window of action for the use of retroviral drugs and for those acting on the immune system.
There is currently no specific drug treatment for COVID-19. Existing drugs used to treat other conditions may be repurposed for COVID-19, and are undergoing clinical trials.
Developing and obtaining regulatory approval for new drugs can take years. Since the emergence of COVID-19, scientists have been working to identify key target sites on the virus for drug treatment and scanning existing drugs to determine if any may be potential candidates to effectively treat COVID-19 infections. Existing drugs have the benefit of already being approved as safe for human use and have established manufacturing arrangements.
NUS researchers are well positioned on the therapeutic development front. The use of Artificial Intelligence to discover new combinations of effective drug and dosing therapy is one of the projects leaded by NUS scientists.
More news on recent discoveries and current projects on COVID-19 led by A*STAR and NUS can be found on their respective websites.
COVID-19: How close are we to a vaccine?
Scientists from companies and universities are taking different approaches to fight the SARS-CoV-2 virus and more than 90 vaccines are now under development around the world.
Source: Fig. 2 in T. Thanh Le et al. Nature Rev. Drug. Disc. http://doi.org/ggrnbr (2020).
A vaccine’s goal is to expose the body to an antigen without causing the disease. However, the antigen will still cause an immune response that can block or kill the virus if a person becomes infected later. The immune system then learns how to fight off the infection if it occurs.
At least five different approaches are being used to increase the chances of finding an effective vaccine: (a) live-attenuated or weakened vaccines, (b) inactivated vaccines, (c) subunit vaccines, (d) DNA and mRNA vaccine, (e) viral vector.
Sources: Nature analysis based on: WHO COVID-19 Vaccine Landscape/Milken Institute COVID-19 Treatment and Vaccine Tracker/T. Thanh Le et al. Nature Rev. Drug. Disc. http://doi.org/ggrnbr (2020)/F. Amanat & F. Krammer Immunity 52, 583–589 (2020)/W. Shang et al. npj Vaccines 5, 18 (2020).
The COVID-19 situation is pushing scientists to accomplish something that was inconceivable a decade ago: create a vaccine against a previously unknown virus rapidly enough to put an end to the outbreak.
Typically, making a new vaccine takes at least a decade. However, new genetic technologies and strategies make researchers optimistic that they can shorten the timeframe to mere months. Even so, making a vaccine for the new coronavirus will take at least one to two years.
Source: Lurie N et al (2020) Developing Covid-19 Vaccines at Pandemic Speed. NEJM. Available at: https://www.nejm.org/doi/full/10.1056/NEJMp2005630 (accessed 7.4.2020)
Some of these technologies have not been applied in licensed vaccines.
A few teams have started clinical trials on humans while others have begun testing on animals.
In Singapore, the Duke-NUS Medical School and United States-based company Arcturus Therapeutics are now conducting pre-clinical studies on a vaccine candidate they have developed. If the vaccine is deemed safe for animals and if studies suggest that it will be the case for humans, it will be used on healthy adults next. Professor Ooi Eng Eong, the deputy director of the emerging infectious diseases programme at the school, said they hope to start clinical trials as soon as August 2020.