As of today, the COVID-19 outbreak has soared past 1.5 million cases across 213 countries, with over 92,000 deaths. What do we know so far from testing for the novel coronavirus to available treatments? We speak to Dr Vinod RMT Balasubramaniam, Virologist & Senior Lecturer at Jeffrey Cheah School of Medicine & Health Sciences, Monash University Malaysia to learn more.
What is the diagnostic kit used now?
“Currently, there are different forms of diagnostic kit being used or being manufactured by various biomedical science/biotechnology companies to detect the COVID-19. We can divide them into 2 main types. One is based on antibodies produced when someone is infected with the SARS CoV-2 (also known as rapid test kits) and another one is more specific which is based on the nucleic acid of the virus. For the first type, usually, when a person is infected, IgM antibodies to SARS-CoV-2 are generally detectable in the blood several days after initial infection, although levels over the course of infection are not well characterized currently (studies being done). IgG antibodies to SARS-CoV-2 become detectable later following infection. Positive results for both IgG and IgM could occur after infection and can be indicative of acute or recent infection. This is usually can be seen in the test strip with colourimetric reaction (similar to pregnancy test kit).
IgG : IgG is the most common type of antibody in our blood and other body fluids. These antibodies protect us against infection by “remembering” which germs we’ve been exposed to before.
IgM : Our body makes IgM antibodies when you are first infected with new bacteria or other germs. They are our body’s first line of defense against infections. When your body senses an invader, your IgM level will rise for a short time. It will then begin to drop as your IgG level kicks in and increases to protect us long-term.
For the second type. It involves the usage of a probe designed specifically complementary to a segment of the virus genome (the whole virus genome was first sequenced by Chinese scientists and its data made available) and detected via quantitative real-time PCR (monitors the amplification of a targeted DNA molecule) (qRT-PCR). Currently, the Ministry of Health is using this type of diagnostic method developed by IMR and CDC as it enables early detection of the SARS CoV-2 compared to antibody-based kits since human antibodies only appear after five to eight days following the coronavirus infection. There are various kits using this qRT-PCR method, for example, Fortitude Kit 2.0 (developed by A*STAR Singapore) and the Abbott’s ID NOWTM platform which is able to detect positive samples within 5 minutes.”
Singapore A*STAR has developed a diagnostic kit that can give a result in 5 min. Is anyone working on a rapid test kit in Malaysia?
“Apart from Singapore A*STAR, there are various Biomedical Science/Biotechnology vendors who have produced their own version of rapid test kits, both antibody and nucleic acid-based which is really fast. For example, is the Abbott’s ID NOWTM platform which is currently being distributed to the US. Similarly, we also have companies in Malaysia producing their own version of the kit, one example being ADT Biotech, which is a Malaysian Bionexus status company, produced “LyteStar 2019-nCoV RT-PCR Kit” for detection of SARS-CoV-2 (the virus which causes COVID-19) — an easy-to-use and sensitive first-line screening assay for the routine diagnostic laboratory. Apart from that, currently, there are various institutes in Malaysia including Tropical Infectious Diseases Research & Education Centre (TIDREC) in Universiti Malaya as well as Universiti Putra Malaysia who are working to produce their own version of the SARS CoV-2 detection kits.”
How do we do research on SARS-CoV-2 virus in Malaysia without a Biosafety Level 4 Lab?
“Biosafety Level 4 Lab is the highest containment system for Infectious diseases. There are only a few labs running in the world with such containment system due to the very high maintenance cost of the lab, examples include the lab in Wuhan Institute of Virology and another one in Galveston, Texas. It is used mainly for experiments involving Class IV pathogens such as Ebola and Marburg viruses. For SARS-CoV-2 work, the CDC (Atlanta) recommends that clinical laboratories handling patient samples such as respiratory specimens, blood (and blood constituents), and urine practice Standard Precautions within a BSL-2 facility. Additionally, work involving full-length genomic RNA should also be carried out at BSL-2. However, activities involving high concentrations of live virus (e.g. propagation or isolation), or large volumes of infectious samples should be performed in no less than a BSL-3 environment.
Most universities in Malaysia including our very own Infectious Disease Laboratory, Jeffrey Cheah School of Medicine, Monash University, Malaysia has the BSL-2 facility in place. Apart from that, selected government agencies such as the Institute for Medical Research (IMR), Veterinary Research Institute (VRI), and National Public Health Laboratory, Sungai Buloh has a completely efficient BSL-3 containment system in place. So, full-fledged research should go on full speed ahead on this virus since we have the facility. Our very own lab was also working on proteins of this virus before the Movement Control Order (MCO) was implemented. So, once the ban is off, research work on the virus can go ahead full speed.”
What are the available drugs out there to treat COVID-19?
“More than 100 off-the-shelf and experimental therapies are being tested either formally or informally for the COVID-19 disease, including hydroxychloroquine, and Remdesivir, an experimental drug from biotechnology company Gilead Sciences Inc. Apart from that, Favipiravir, a previously approved anti-influenza drug has also shown promise in a study conducted in China. However, most of these studies are done in small groups and some of it only in vitro. We need proper large randomized clinical trial data to support and evaluate the efficacy of these repurposed drugs. This should be faster since almost all of these drugs have been given approval by the Food and Drug Administration (FDA) previously.
One such effort being the one initiated by WHO (Malaysia included) which is currently planning to test global large scale efficacy of Remdesivir among COVID-19 patients. Remdesivir is currently being looked at as the most promising drug candidate by the WHO panel for further trials and testing. If these proven to be efficient it should be available for everyone, especially those who are immunocompromised (elderly, children, pregnant women etc). Until then, it is really hard to conclude the efficiency of these drugs especially its use in combination.”
“Remdesivir was originally designed to tackle Ebola by inhibiting an enzyme called RNA polymerase that is used by many viruses to replicate, though it never succeeded in that indication. In a 2017 Science Translational Medicine (journal) study, scientist found the drug could also kill SARS and MERS—two other coronaviruses that caused deadly outbreaks in the 21st century—in lab dishes. However, it’s efficacy in humans still needs to be carefully studied since it lacks randomized clinical trial data especially in COVID-19 patients. Therefore this effort by WHO to test its efficacy is much needed, if proven successful, it could save thousands of lives not only in Malaysia but globally.”
Chloroquine phosphate, an old drug for the treatment of malaria, has also shown to have apparent efficacy and acceptable safety against COVID-19. How effective is it?
“Chloroquine was first used as prophylaxis and treatment for malaria. Hydroxychloroquine is a more soluble and less toxic metabolite of chloroquine, which causes less side effects and is, therefore, safer. Several in vitro studies (Yao et al 2020 and Gautret et al 2020) report antiviral activity of chloroquine and hydroxychloroquine against SARS-CoV-2. In vivo data, although promising, is currently limited to one study with considerable limitations. On the basis of the weak evidence available to date, treatment guidelines have already incorporated the usage of chloroquine/hydroxychloroquine for certain patients with COVID-19. Further research should address the optimal dose and duration of treatment, and explore side effects and long-term outcomes. There is a higher risk of side effects in the presence of renal and liver impairment, and there have been isolated reports of COVID-19 disease-causing renal and hepatic injury. Over twenty in vivo clinical trials have already been registered to test the use of chloroquine and hydroxychloroquine for the treatment of COVID-19.”
A man in Arizona, US died after taking chloroquine phosphate, which is used in aquariums. What went wrong?
“The man in Phoenix, Arizona appears to have taken an additive version of the drug (which is also used to wash aquariums) and not the pharmaceutical grade in an attempt to cure himself from the COVID-19. So, misinformation/miscommunication regarding the substance played a role in this, since the use of the drug was touted as a possible treatment for COVID-19, in news and was even announced by President Trump without credible randomized human clinical trial data. The man died of obvious hepatotoxicity.”
Bionotes of experts
Dr Vinod RMT Balasubramaniam graduated from Asian Institute of Medicine, Science and Technology (AIMST) majoring in Biotechnology in 2007. During this period, he managed to publish several papers on plant genetic engineering, especially on genetically engineered orchids which have resistance towards fungus. In 2008, he worked as a research assistant with Associate Professor Sharifah Syed Hassan in her newly formed infectious disease laboratory in Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia. He embarked on his PhD course working on the various host cellular genes infected with Avian Influenza Virus H5N1 and their protein-protein interactions with viral genes. Graduated with merit in 2014, he continued to work as a post-doctoral fellow before joining Professor Adolfo Garcia-Sastre’s laboratory in Mount Sinai hospital New York, which is one of the leading Influenza research laboratory in the world. He has co-authored various publications (Cell Host Microbe, Nature Microbiology, Plos Pathogens) on various aspects of host response towards different types of viruses.
**All previous posts about COVID-19 here: https://sciencemediacentremalaysia.com/tag/covid-19/