The global COVID-19 pandemic picture is still unclear as the novel coronavirus outbreak shifts constantly around the world. While the number of cases rise critically in South America’s first wave, the UK and European countries have begun to lift their lockdown measures amidst this COVID-19 pandemic. At the same time, South Korea and China, where coronavirus cases seemed to have disappeared, have seen a second wave of infections. However, a common question emerges among this COVID-19 rollercoaster: Will we have a vaccine soon?
A matter of time
Timing is crucial in vaccine research. More than five months have passed since the genetic sequence of SARS- CoV-2, the virus that causes COVID-19, which was published on 11th January 2020. This discovery sparked an unprecedented global research effort to develop a vaccine against this disease1, involving next-generation technology platforms and novel approaches with a hope to speed up this process. However, vaccine development involves a multi-stage process of research and testing, which typically takes more than ten years to be completed2 (Fig. 1). Therefore, we must remain cautious in light of a new vaccine.
What is the current picture?
A recent overview of the global landscape of COVID-19 vaccines by the World Health Organisation (WHO) included more than 140 vaccine candidates from different research groups and developers around the world3. From those, 129 candidate vaccines are under preclinical evaluation, which means a preliminary laboratory exploration but not yet in human trials. On the other hand, 13 candidate vaccines have entered the clinical evaluation stage, which is a three-phase process involving human subjects (Fig. 2).
OK, but can we speed up this process?
In terms of vaccine research time we are progressing at super-fast speed in this scenario. Just consider that the first set of COVID-19 cases, a new type of viral pneumonia, were reported to WHO on 4th January 2020 (Fig.3). Two months later, the first COVID-19 vaccine entered first-in-human trials within record breaking time on 16th March 2020. Scientists and international organizations around the world are still racing to produce and deliver a safe and effective vaccine within an 18-month period1-3.
So, do we have a vaccine yet?
From the array of advanced COVID-19 candidates under clinical development, only one promising study has started their phase 3 trial in Brazil4 (Fig. 4). This a non-replicative viral vector vaccine developed by the University of Oxford and the British-Swedish company AstraZeneca5. As we previously described, this candidate works as an inactive vaccine by using a different non-live virus to deliver coronavirus genes into our cells. In other terms, it can´t reproduce itself but it can still provoke an immune response.
Currently, this vaccine is also moving to Phase II/III in England and will hopefully deliver positive results by next year. A different approach has been employed by The Murdoch Children’s Research Institute in Australia. The experimental coronavirus vaccine, which is currently in phase 3 trial, utilises the Bacillus Calmette-Guerin vaccine6. The BCG vaccine is made from a weakened strain of tuberculosis bacteria and been widely used since the 1920s to fight TB7.
Researchers expect to observe partial protection against SARS-COV-2 as observed for other diseases7,8. Only data and results will decide if the remaining vaccine candidates could progress to phase 3 human trials and if this global effort could be translated into a successful vaccine by early 2021.
Usher AD. COVID-19 vaccines for all?. Lancet. 2020;395(10240):1822-1823. doi:10.1016/S0140-6736(20)31354-4
Thanh Le T, Andreadakis Z, Kumar A, et al. The COVID-19 vaccine development landscape. Nat Rev Drug Discov. 2020;19(5):305-306. doi:10.1038/d41573-020-00073-5
On May 10th, 2020 the UK Government announced that Secondary Schools, Sixth Forms and Further Education Colleges could provide some face-to-face support for year 10 and year 12 students after June 1st 2020. This was subsequently deferred to start on 15th June (1). Students in these year groups have national exams in Summer 2021. This means this time in year 10 and year 12 is critical as the bulk of the curriculum is delivered.
To reduce the spread of COVID-19 in schools on the return of students, the government has advised the regular cleaning of frequently touched surfaces, changing classroom layouts to reduce student contact and to stagger timetables (2). However, what are the students’ views on returning to school?
It was important to me to get this question answered, so I designed a study in aim to voice the views of students.
Why is this research important?
It is not apparent that the Government has engaged with the school students affected most by this decision. Students have not been given a platform to raise their concerns about returning to education. Their views have not been heard.
This motivated me to conduct a prospective study to collate the views of young people and publicise their concerns. It is important to involve young people in decisions that affect their situation so that they engage with the policy (3). Year 10 and year 12 students are also of an age where their opinions should be taken into account.
Aims of the research project:
This study was conducted to explore the opinions of year 10s and 12s concerning returning to partial school after the first wave of the covid-19 outbreak in June 2020. The aim was to provide a voice to young people on returning to partial schooling in June 2020.
Students were invited to express:
Their preferences on returning to school
Their views about safety with respect to government guidance on return to school
How they feel COVID-19 will impact on their future
How COVID-19 has impacted on their education
This study will inform members of the public and policy makers about the opinions of year 10 and 12 students returning to school in the UK at the end of the first wave of the SARS-CoV-2 outbreak.
How the research was conducted:
The aims of this study were addressed with qualitative research using a prospective survey conducted from the 20th to 27th May 2020. Participants were year 10 (age 14 to 15 years old) and year 12 (age 16 to 17 years old) school students in the United Kingdom.
A 12-question survey was compiled on Google Forms™ with 9 close-ended questions and 3 open-ended questions. The survey was distributed to the students via two online Facebook™ forums specific to their year groups: The A level Forum (6,500 members) and a GCSE forum (36,000 members). The survey was accessible on multiple platforms (computers and smartphones) and multiple web browsers.
The 3 open ended questions were subject to Braun and Clarke themed analysis. Thematic analysis is a method for identifying and interpreting patterns of meaning across qualitative data. This meant recurring themes in the written data could be addressed and the reasons behind students’ answers could be found without influence. Braun and Clarke analysis provides a qualitative six phased method of thematic analysis. Firstly, I familiarised myself with the qualitative data and noted general ideas. NVIVO (v12) software was used to group the qualitative data into codes (similar patterns in the data). Themes were then put together by grouping the codes. I then reviewed and defined each theme in relation to the research measures.
There was a rapid uptake from students with 1534 responses in 7 days.
Year 10 and 12 school students are evenly divided in opinion about whether they should return to school on 15th June. This uncertainty appears based on the majority of students having concerns about schools’ ability to comply with government guidance, particularly around social distancing and the risk of transmission. Some students recognised a need to return to education despite this perceived risk. This uncertainty could be addressed by better engagement from policy makers with school students. School students expressed desire that their students’ concerns are addressed by the Government and better explanation of the reasoning behind returning certain students to school at this time whilst other members of the community continue to isolate.
Policy makers should standardise remote learning. This will ensure all students receive some educational support during pandemics, ensuring the educational divide caused by a lockdown is minimized.
1. Actions for schools during the coronavirus outbreak [Internet]. GOV.UK. 2020 [cited 2020 Jun 9]. Available from: https://www.gov.uk/government/publications/covid-19-school-closures/guidance-for-schools-about-temporarily-closing
2. Coronavirus (COVID-19): implementing protective measures in education and childcare settings [Internet]. GOV.UK. 2020 [cited 2020 Jun 9]. Available from: https://www.gov.uk/government/publications/coronavirus-covid-19-implementing-protective-measures-in-education-and-childcare-settings/coronavirus-covid-19-implementing-protective-measures-in-education-and-childcare-settings
3. Mitchell C. “The Girl Should Just Clean Up the Mess”: On Studying Audiences in Understanding the Meaningful Engagement of Young People in Policy-Making. Int J Qual Methods [Internet]. 2017 Dec 1 [cited 2020 Jun 6];16(1):1609406917703501. Available from: https://doi.org/10.1177/1609406917703501
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.