COVID-19, caused by SARS-CoV-2, currently has no available cure or vaccine (although not through lack of trying!). At the moment we have to rely on supportive treatments to alleviate symptoms; these can range from taking antipyretics like paracetamol at home to reduce a fever, to mechanical ventilation in intensive care units. It can be scary to face an illness where the only options for patients are to manage symptoms and wait for recovery, so are there any other treatments that could be explored? The Chinese government seem to think so: during the peak of the epidemic in China more than 85% of those treated for COVID-19 in hospitals also received treatment with traditional Chinese medicine (TCM).
What is traditional Chinese medicine?
TCM has been used for thousands of years to treat a whole host of illnesses. It differs a bit from the ‘old wives tales’ you might associate with alternative medicine in that it is based on a theory of ‘syndrome differentiation’; patients are treated according to their individual symptoms, using a holistic approach. This differs from the typical disease-specific treatment offered by conventional medicine, in which the patient’s diagnosis will determine their treatment. TCM can include physical therapies such as acupuncture or targeted exercise, but here we are focusing on herbal medicines, comprised of a mixture of ingredients tailored to an individual’s symptoms. These are usually taken in the form of teas, broths or powders. The Chinese government are currently endorsing a combination of conventional medicine and TCM to treat COVID-19, so could this have any benefit to patients?
Does it actually work?
A huge number of COVID-19 patients in China are receiving TCM. A variety of treatments are in use as each case is taken individually, so there is no standardised “treatment”against COVID-19. One of the more common suggested TCM formulations is Qing Fei Pai Du Tang, a composition of 21 different herbal substances claimed to aid in ‘ventilating the lungs’. This has been widely used in China by COVID-19 patients and is commercially available but contains ingredients which are banned in a number of other countries. The national administration of traditional Chinese medicine claims that after the treatment of a group of 214 patients with this remedy, 60% improved over the course of treatment, with 30% showing stabilisation of their condition. Supporters of TCM claim that remedies can shorten the duration of symptoms by up to 2 days, reduce the chance of illness becoming severe, and provide relief from symptoms such as cough and fever. Usually these claims are supported by anecdotal evidence, for example a bus driver in Wuhan who was admitted to hospital for COVID-19 symptoms. In additional to conventional supportive care he was given a herbal broth, and following a few days of treatment his symptoms subsided. These claims all sound very promising, but how much of this can we believe?
Headline taken from The Economist, 11 April 2020.
TCM makes bold claims about its ability to treat conditions like COVID-19, but how are these claims backed up? As explained above, anecdotal evidence is key in the claims proponents of TCM make. Often individual patients’ recovery after treatment is taken as definite evidence of its efficacy. In the case of COVID-19 in particular, this is suspect as the vast majority of cases resolve quickly and do not progress to severe illness; the patients who are held up as an example of the success of TCM would have likely recovered on their own without intervention. Clinical trials investigating the use of TCM do exist, including those conducted during the 2002-2004 SARS epidemic. However, these trials are frequently funded by those with a vested interest in proving the effectiveness of TCM and are poorly controlled with significant flaws in methodology. While at the time of the SARS epidemic it was claimed that TCM may be beneficial to patients, literature reviews since have shown no difference in mortality between those receiving both TCM and conventional medicine, and conventional medicine only. There are at least 50 ongoing clinical trials examining TCM in China, but again results from these will need to be taken with cation as these are not the double blind, placebo-controlled trails that are the standard in evidence-based medicine.
But it’s just herbs, right? What’s the harm?
Despite the lack of evidence for the efficacy of holistic treatments like TCM, many people are still tempted to try them because they are presumed to be ‘natural’ and therefore safe. Aside from not being proven effective, they can also be harmful. TCM is very poorly regulated in most countries; in the UK, TCM is monitored by the medicines and healthcare products regulatory agency (MHRA) but they aren’t actually tested before being put on the market. Instead, manufacturers are relied upon to accurately declare the contents of their products. One research group in Australia set out to test how reliable this information was. 26 different TCM formulations were purchased over the counter and examined for three key areas of non-compliance to the standards needed for legal sale: presence of undisclosed animal DNA, presence of heavy metals (lead, arsenic or cadmium), and adulteration with pharmaceutical products.
Their results were, frankly, frightening, 92% of the TCM remedies tested contained some form of contamination not disclosed on the ingredients list. Half the tested samples contained DNA of an animal not listed, ranging from snow leopard to rat. Ingredients derived from endangered species like leopard and shark are often added deliberately for their perceived therapeutic benefits, but others such as rat, mouse and cat DNA could indicate serious contamination issues during manufacture. The number of TCM formulations containing heavy metals was also concerning. More than 75% of the 25 tested samples contained at least one heavy metal, with 15 exceeding the recommended daily dose. Several samples even contained more than 10 times the maximum daily dose of lead!
Other research has indicated that up to a quarter of TCM formulations contain undeclared pharmaceuticals, but another study found that the true number could be closer to half. More than 50% of tested samples contained at least one pharmaceutical adulterant, many of which were at clinically significant doses. One such TCM contained six pharmaceutical products at doses which would normally require a doctor’s prescription, including amoxicillin and warfarin. None of these were mentioned on the label, and the interactions of a medicine containing analgesics, antibiotics, stimulants and antihistamines aren’t certain. As well as proving potentially dangerous to patients, pharmaceutical adulterants can distort the data from any clinical trials of these TCM formulations. It is very likely that any TCM product containing a clinically relevant dose of an undisclosed pharmaceutical would outperform a placebo, so this gives false data about the efficacy of the TCM formulation itself. These pharmaceuticals are often added to give the desired effect without being listed as part of the formulation of the TCM, so it is very difficult for patients to know what they are getting.
Adapted from Coghlan et al, 2015.
Overall, all but two of the 26 formulations tested were non-compliant with standards posed by Australian regulations, which are very similar to UK MHRA standards. It is concerning that these so-called medicines, which could actually pose a serious health risk in some cases, can be commercially available without a transparent ingredients list. Given TCM formulations are being given to patients ill with COVID-19, it is possible for them to cause harm. Holistic treatments marketed as ‘natural’ can have sinister effects or ingredients, so it is extremely important to discuss any alternative therapies with a doctor.
So why are we talking about it?
Although TCM may be ineffective or even dangerous, some ingredients could hold promise for treatments of viral infections including COVID-19. Natural products can be isolated from plant extracts that make up TCM remedies; some of these possess real therapeutic benefit. For example, artemisinin is a current frontline therapy used in the treatment of malaria. In 1971, Chinese scientist Youyou Tu extracted this compound from wormwood, a traditional remedy for fever, and found it was able to cure malaria in mouse and primate models. She later won a Nobel prize for her work. Another example is the finding that an extract from the common TCM ingredient liquorice root, known as glycyrrhizin, showed activity against a strain of coronavirus isolated during the SARS epidemic. When present in very high concentration (4000mg/L), glycyrrhizin was able to fully inhibit viral replication. This seems promising, but the mechanism for this isn’t fully understood and a lot more research is needed before any compound derived from TCM could be used as a treatment for SARS-CoV or indeed COVID-19.
TCM and other holistic therapies are clearly very divisive. Some wholeheartedly believe in their power, having heard anecdotes of miraculous cures. Others write it off completely due to the lack of good science or reliable evidence of its effectiveness. In truth, there is likely to be some benefit to investigating TCM as a potential treatment for COVID-19, just perhaps not in the way it would traditionally be applied. A huge number of potential drug candidates in the form of natural products may be present in the ingredients that make up TCM formulations. For these to be useful as medicines in the fight against COVID-19 and other viral infections, there needs to be rigorous testing, valid and reliable clinical trials, and thorough and transparent regulation of emerging treatments.
- Fung, Y. F. and Linn, Y. C. 2015. Developing Traditional Chinese Medicine in the Era of Evidence-Based Medicine: Current Evidences and Challenges. Evidence-Based Complementary and Alternative Medicine.2015, article no: 425037 [no pagination].
- Yang, Y., Islam, M. S., Wang, J., Li, Y., and Chen, X. 2020. Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective. International Journal of Biological Sciences.16(10), pp1708-1717.
- Ren, J. L., Zhang, A. H., and Wang, X. J. 2020. Traditional Chinese Medicine for COVID-19 Treatment. Pharmacological Research.155, article no: 104743 [no. pagination].
- Xu, X. W. et al. 2020. Clinical Findings in a Group of Patients Infected With the 2019 Novel Coronavirus (SARS-CoV-2) Outside of Wuhan, China: Retrospective Case Series. The bmj.8235, article no:2020;368:m606 [no pagination].
- Coghlan, M. L., Maker, G., Crighton, E. et al. 2015. Combined DNA, Toxicological and Heavy Metal Analysis Provides an Auditing Toolkit to Improve Pharmacovigilance of Traditional Chinese Medicine (TCM). Scientific Reports. 5, article no: 17475 [no pagination].
- Tu, Y. 2011. The Discovery of Artemisinin (Qinghaosu) and Gifts from Chinese Medicine. Nature Medicine. 17, pp1217-1220.
 Cinatl, J. et al. 2003. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. The Lancet. 361, pp2045-2046.
Viral diseases have shaped human history. A sudden emergence has the power to cause huge social changes, like ones we’re currently experiencing. But how do they do this? What causes a virus to jump, or ‘spill over’ into a new species?
What is an emerging virus and how do they emerge?
An emerging virus is a virus which has entered a new population where it previously didn’t exist or is expanding its geographical range. Global disease emergence is increasing for many reasons and we’ll discuss why this is occurring and why most emerging viruses that normally infect animals are now infecting humans.
What’s important to remember is there are no singular reasons for viral disease emergence, and we might never know what occurred to cause a disease to break into new populations. But there’s many ways this can happen, ranging from the virus’s genetics all the way through to human-environment interactions. Here we’re going to focus on RNA viruses as these are the viruses which most commonly cross species barriers1. Let’s start with the genetics first.
RNA viruses contain an enzyme called RdRp. This enzyme replicates RNA. RNA is a form of genetic code like DNA, so it encodes genes. However, RdRp is prone to making mistakes, it might miss a base, it might use the wrong one and its common for this to happen. This means a virus can be produced with different properties, this can range from being able to target a new cell type to replicating faster. One case where this occurred was during the 1918 Spanish Flu, where a mutation allowed the virus to replicate in tissues outside the respiratory tract2.
Reassortment of segmented genomes
Reassortment is the process where genetic material might get ‘mixed up’. When a cell is infected with two different but closely related viruses there’s a chance this might occur. Think of it like mixing your favourite drinks. It could work, and you might have a new flavour, or it might not! It’s easier for segmented genomes, so the genetic code is in multiple segments and is common in viruses like influenza. H1N1 is an influenza virus which is made up of bird, pig and human influenza strains3.
Recombination of RNA genomes
Recombination is a random event which occurs when RdRp, the enzyme which makes new RNA, falls off the genome its copying onto a different one. It ultimately will produce an RNA genome which is a combination of two different viruses. This is another common event and many virus families have evidence of this occurring, including Herpesviruses, HIV and even Coronaviruses4,5.
Changes in weather
Climate change isn’t only impacting our weather, it’s also changing disease distributions through temperature but also causing changes in host territory. Ultimately this changes how we interact with hosts of viruses as well as their biology. For example, Japanese Encephalitis Virus (JEV). This virus is carried by mosquitoes, so a higher temperature alters host territory as well as allowing for mosquito development to occur where it didn’t previously. This is because mosquitos have a minimum temperature where development will occur, and for the mosquito which carries JEV its 22-23 °C. However, viral diseases can have a minimum transmission temperature, and JEV has one of 25-26 °C. If more countries have temperatures above this range, then the virus can be transmitted in new populations. What this all means is as global temperatures rise it’s very likely countries will experience diseases they haven’t previously6.
Bush meat and live animal markets
Consumption of bush meat and live animal markets remove natural barriers in place, meaning that close contact between animals and humans now occurs. Outbreaks may occur due to consumption of an animal which died of a disease, and not of more natural causes. This is how Ebola outbreaks have started before. However, it is important to consider the socio-economic conditions found within regions where consumption of bush meat occurs. Protein sources in these regions can be expensive and the local population may not have the choices we do7. Reducing disease emergence from live animal markets can be done safely by reducing inter-species interactions, essentially handling the animals less and making the markets less crowded. However, it could also be done through limiting the days of operation8.
Changing land use and farming practices
Deforestation of land for farming and urban development is forcing disease hosts to come into closer contact with humans, one example where this is occurring is Australia. Here, horse farms are traditionally where fruit bats reside however urbanisation has resulted in loss of the natural habitat, forcing greater interactions with the human population9.
So, there we have it. Several mechanisms on how viruses can emerge into human populations. But what about SARS-CoV-2? Well, the jury’s still out. Though early cases were linked to a seafood market many weren’t, indicating the source of the virus likely wasn’t here. In the meantime, scientists will be hard at work hoping to solve many puzzles, including this! If you have any questions about what was discussed drop us a message below or on Facebook, Twitter or Instagram and we’ll get back to you.
For more information on the origins of SARS-CoV-2 read our blogpost breaking down a Nature paper by Dr Jordan Clark here.
For more information on viral disease emergence check out ‘Spillover’ by David Quammen.
1.J Woolhouse, M. E., Adair, K. & Brierley, L. RNA Viruses: A Case Study of the Biology of Emerging Infectious Diseases. Microbiol. Spectr.1, 10.1128/microbiolspec.OH-0001–2012 (2013).
2.Taubenberger, J. K. The origin and virulence of the 1918 ‘Spanish’ influenza virus. Proc. Am. Philos. Soc.150, 86–112 (2006).
3.Vijaykrishna, D. et al. Reassortment of pandemic H1N1/2009 influenza A virus in swine. Science328, 1529 (2010).
4.Fleischmann, W. J. Medical Microbiology. (University of Texas Medical Branch, 1996).
5.Su, S. et al. Epidemiology , Genetic Recombination , and Pathogenesis of Coronaviruses. Trends Microbiol.24, 490–502 (2016).
6.Wu, X., Lu, Y., Zhou, S., Chen, L. & Xu, B. Impact of climate change on human infectious diseases : Empirical evidence and human adaptation. Environ. Int.86, 14–23 (2016).
7.Kurpiers, L. A., Schulte-Herbrüggen, B., Ejotre, I. & Reeder, D. M. Bushmeat and Emerging Infectious Diseases: Lessons from Africa BT – Problematic Wildlife: A Cross-Disciplinary Approach. in (ed. Angelici, F. M.) 507–551 (Springer International Publishing, 2016). doi:10.1007/978-3-319-22246-2_24
8.Karesh, W. B., Cook, R. A., Bennett, E. L. & Newcomb, J. Wildlife trade and global disease emergence. Emerg. Infect. Dis.11, 1000–1002 (2005).
9.Plowright, R. K. et al. Urban habituation, ecological connectivity and epidemic dampening: the emergence of Hendra virus from flying foxes (Pteropus spp.). Proceedings. Biol. Sci.278, 3703–3712 (2011).