Expert Reaction on COVID-19

By Dr Vinod A/L RMT Balasubramaniam

What is the diagnostic kit used now? How does it work? Who produced it?

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 two 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 the initial infection. However, levels throughout infection are not well characterised 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 seen in test strips 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 defence 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. Various kits are using this qRT-PCR method, for example, Fortitude Kit 2.0 (developed by A*STAR Singapore) and the Abbott's ID NOWTM platform which can detect positive samples within 5 minutes.

Singapore A*STAR just 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, various Biomedical Science/Biotechnology vendors have produced their version of rapid test kits, both antibody and nucleic acid-based, which is fast. For example, is Abbott's ID NOWTM platform, which is currently being distributed to the US. Similarly, we also have companies in Malaysia producing their 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 TIDREC UM and UPM who are working to produce their version of the SARS CoV-2 detection kits.

How do we research SARS-CoV-2 virus in Malaysia without a Biosafety Level 4 Lab?

Biosafety Level 4 Lab is the highest containment system for Infectious diseases. Only a few labs are 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 MCO was implemented. So, once the ban is off, research work on the virus can go ahead full speed.

WHO has chosen Malaysia as one of the countries that will conduct joint research on the Remdesivir drug that is used to treat the Covid-19 infection. What is the significance of this?

Remdesivir was initially designed to tackle Ebola by inhibiting an enzyme called RNA polymerase that's 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 randomised 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, is shown to have apparent efficacy and acceptable safety against COVID-19. How effective is it? A man in Arizona, US died after taking chloroquine phosphate, which is used in aquariums. What went wrong?

Chloroquine was first used as prevention 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. Based on 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. 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 of 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 the news and was even announced by President Trump without credible randomised human clinical trial data. The man died of obvious hepatoxicity.

Health DG, Dr Noor Hisham Abdullah said chloroquine, hydroxychloroquine and a combination of lopinavir and ritonavir could be used to treat Covid-19. This includes imported Favipiravir dan Remdesivir. Which is the most effective and who should take them?

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 extensive randomised 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 approved by the 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 presently 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 tough to conclude the efficiency of these drugs, especially its use in combination.

WHO is considering "airborne precaution" for medical staff. Is the Covid-19 airborne? If yes, how long does it stay in the air and how far can these viral particles travel?

COVID-19 spreads through human-to-human contact, droplets carried through sneezing and coughing as well as germs left on inanimate objects. The coronavirus can go airborne, staying suspended in the air depending on factors such as heat and humidity. New studies show that the virus was detectable in aerosols for up to three hours, up to four hours on copper and up to 24 hours on cardboard. The new coronavirus can also last up to three days on plastic and stainless steel, adding the amount of the virus left on those surfaces decreases over time. Aerosols are solid or liquid particles that hang in the air, including fog, dust, and gas commonly used in medical procedures like ventilation and nebulisers (published in New England Journal of Medicine, N van Doremalen, et al. 2020). It is also postulated that the virus particles can travel up to 6 feet in distance.

How long does the virus survive on surfaces such as hair, clothes, materials, hands, packages, etc.?

Generally, smooth, nonporous surfaces like doorknobs and tabletops are better at carrying viruses in general. Porous surfaces – like money, hair, and fabric – don't allow viruses to survive as long because the small spaces or holes in them can trap the microbe and prevent its transfer.

Can COVID-19 be passed from a pregnant woman to the fetus or newborn? Is there any guidance on breastfeeding for mothers with confirmed COVID-19?

According to the CDC, it is still unknown if a pregnant woman with COVID-19 can pass the virus that causes COVID-19 to her fetus or baby during pregnancy or delivery. No infants born to mothers with COVID-19 have tested positive for the COVID-19 virus. In these cases, which are a small number, the virus was not found in samples of amniotic fluid or breastmilk. Studies are being carried away to test this. Hence, for now, there are no restrictions on mothers who have tested positive for COVID-19 to breastfeed their babies. However, the following precautions should be taken:

  • Practice respiratory hygiene during feeding, wearing a mask where available;
  • Wash hands before and after touching the baby;
  • Routinely clean and disinfect surfaces they have touched.

Can Vitamin C supplements stop you from catching COVID-19?

This is a myth which is currently going on around the people. Vitamins C is essential in general health well-being. However, it has no role or efficacy in "boosting" the immune system nor stopping people from catching the COVID-19. This is an infectious disease caused by the pathogen SARS CoV-2. The virus has animals as intermediates (such as bats and pangolins) which can transmit the virus - hence causing the disease.

Apart from masks, we start to see people wearing gloves in supermarkets. Will wearing gloves protect you from Covid-19?

Generally, proper PPE (Personal Protective Equipment) help to contain the spread/transmission of the SARS CoV-2. However, it should be appropriately administered and disposed of. The use of a proper rubber/latex gloves generally protects us from getting COVID-19 since the virus responsible, SARS CoV-2 can remain active/viable in most surfaces especially in a place like supermarkets where there will be a crowd and lots of movements. However, the use of gloves should only be single-use and should be complemented with proper face masks for better protection.