As we delve into this new series – a scientists’ toolkit, we start with the microscope. From its history through to its applications. Its uses are endless and we will show you why!
There are many different types, from light to electron, some are binocular others are not. There are digital, stereo, USB and pocket microscopes. Here are just a few of them below. Depending on the purpose different microscopes may be used, it is just about picking the right one for the job! (7)
Digital light microscope: invented in Japan in 1986. Uses principles of light microscopy, but connects to a computer similar to a printer/ Allowing for ease of observation. (7)
Stereo light microscope: Also known as a dissecting microscope, is used to view images three dimensionally by having 2 optical paths. (7)
Electron microscope: more powerful than a light microscope, and allows scientists to see things at nano size, there are two types; the scanning and transmission type. (7)
Microscopes are used by scientists for lots of different reasons- primarily to observes microscopic structures, and changes that cannot be seen by the naked eye. Allowing scientists to understand structure and physiology. This can help when trying to understand normal processes in the body, as well as changes due to disease, the effect of different therapies on the body, and possible therapeutic targets.
They can be used to visualize structures, conduct cell counts, diagnose disease and conduct qualitative scoring.
A second simultaneous Ebola outbreak has been confirmed in the Democratic Republic of Congo (DRC), (World Health Organization, 2020). This marks the 11th Ebola outbreak in central Africa which comes at a time when the continent also battles the COVID-19 pandemic.
First discovered in 1976, ebola viruses have since re-emerged across the African continent. The virus reached international attention during the longest and most extensive Ebola outbreak in West Africa between 2013 – 2015.
Historical Ebola outbreaks have fatality rates as high as 88%, almost 9 out of 10 people would die as a result of infection. The West Africa outbreak, however, saw a drastic reduction in fatality rate, to around 40%. The reduction in fatality rate was likely a result of the increased basic support, advanced and more appropriate care for those infected and earlier case detection, allowing for better management of both patients and outbreak spread (Baseler et al., 2017).
The most recent outbreak is in Mbandaka in the Équateur region, 600 miles from the ongoing Kivu Ebola epidemic in the North Kivu and Ituri provinces. The cases in Mbandaka are thought to be separate from the Kivu Ebola epidemic and instead the result of a new ‘spillover’ event from an animal reservoir to humans.
As of the 10th of June, a total of 12 cases have been reported; 9 confirmed cases, 3 suspected cases and 6 deaths, (Bujakera, Holland and Heavens, 2020)*. Positive samples were confirmed via testing at the Institut National de Recherche Biomédicale (INRB) – the countries national medical research organisation.
Although case number is relatively small at present, this is likely to rise as contacts are traced and the incubation period of 2-21 days elapses. Whilst the outbreak has presented at an already challenging time, scientists and doctors are on the ground with capacity to trace and diagnose. This service was expanded and refined in 2018 in response to previous outbreaks (World Health Organization, 2020).
The Kivu Ebola epidemic began in August 2018, over 3,400 people have been infected and sadly 2,200 lives lost despite the implementation of aggressive control measures. A number of factors have hindered this operation including; stigmatization, civil unrest and logistical issues.
Community level prevention and outbreak measures are dependent on the public trusting local authorities, however 31.9% of 961 individuals surveyed in North Kivu trusted that local authorities were acting in their best interests. The same survey reported 25.5 % of those surveyed believed the outbreak was a hoax, (Vinck et al., 2019). Complicating this were populist politicians publishing their own doubts on the outbreak validity to gain support in the 2018 elections. The country had not yet had a peaceful transition of power since decolonialisation in 1960, (Moran, 2018).
However, deployment of an experimental vaccine, coupled with rapid diagnostics helped to halt the outbreak. Following emergency use in 2016, the Ervebo vaccine was finally approved for use in 2019, after clinical trial demonstrated safety and efficacy; 97.5% efficacy in preventing Ebola infection compared to no vaccination, (Regules et al., 2015; World Health Organization, 2019).
Although an effective vaccination is now available, this is by no means the end of the problem. Availability, difficulties in contact tracing and public perception are all challenges that must be addressed to manage the outbreak during an already arduous time.
It is hoped that authorities and individuals alike can action their learnings from previous outbreaks, to bring this new outbreak to a swift end.
The DRC is currently contending with outbreaks of cholera, SARS-CoV-2, measles and two separate Ebola clusters. This serves as a stark reminder that whilst the world fights against the SARS-CoV-2 pandemic, Ebola outbreaks will stop for no country and no person.
Viruses emerge, or spillover often in nature, ebola virus is an example of this. Check out our blog on viral emergence here, or our post about bats and viruses.
*Please note that this article is not by a scientific body and reports figures from a WHO press conference which could not be confirmed on WHO.int.
Written by Charlotte Rigby
Baseler, L. et al. (2017) ‘The Pathogenesis of Ebola Virus Disease’, Annual Review of Pathology: Mechanisms of Disease, 12(1), pp. 387–418. doi: 10.1146/annurev-pathol-052016-100506.
Bujakera, S., Holland, H. H. and Heavens, A. (2020) Up to 12 infected in Congo’s new Ebola outbreak: WHO, Reuters.
Moran, B. (2018) ‘Fighting Ebola in conflict in the DR Congo’, The Lancet. Elsevier, 392(10155), pp. 1295–1296. doi: 10.1016/S0140-6736(18)32512-1.
Regules, J. A. et al. (2015) ‘A Recombinant Vesicular Stomatitis Virus Ebola Vaccine’, New England Journal of Medicine. Massachusetts Medical Society, 376(4), pp. 330–341. doi: 10.1056/NEJMoa1414216.
Vinck, P. et al. (2019) ‘Institutional trust and misinformation in the response to the 2018–19 Ebola outbreak in North Kivu, DR Congo: a population-based survey’, The Lancet Infectious Diseases, 19(5), pp. 529–536. doi: https://doi.org/10.1016/S1473-3099(19)30063-5.
World Health Organization (2019) Preliminary results on the efficacy of rVSV-ZEBOV-GP Ebola vaccine using the ring vaccination strategy in the control of an Ebola outbreak in the Democratic Republic of the Congo: an example of integration of research into epidemic response. doi: 10.1016/j.surfcoat.2019.125084.
World Health Organization (2020) New Ebola outbreak detected in northwest Democratic Republic of the Congo; WHO surge team supporting the response. Available at: https://www.who.int/news-room/detail/01-06-2020-new-ebola-outbreak-detected-in-northwest-democratic-republic-of-the-congo-who-surge-team-supporting-the-response (Accessed: 2 June 2020).
Written by Rebekah Penrice-Randal and Lucia Livoti
Features of 20,133 UK patients in hospital with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study 1 was published in The British Medical Journal (BMJ) this week. This report defines clinical characteristics of patients in hospital in the UK, using the ISARIC WHO Clinical Characterisation Protocol. We have written a brief summary to define what this means, discuss the report itself and highlight the key findings to aid public understanding.
You can follow the study on twitter for more updates: @CCPUKstudy
What is the ISARIC WHO Clinical Characterisation Protocol?
A research protocol is the set of documents that includes the instructions for conducting a study, the participant information sheets and consent forms. A clinical research protocol has to be approved by an independent Research Ethics Committee to ensure patient safety and dignity, and in the UK, by the Health Research Authority to ensure that health care resources are used appropriately.
In other words, the study was set up in advance of an outbreak to ask the “who, what and why” of a new disease. Who is affected means, age, sex, ethnicity and underlying medical problems. What means, what does the disease cause any of: breathing problems, diarrhoea, vomiting, sepsis or bleeding.
The ISARIC WHO CCP allows for the collecting of clinical data and biological samples, and their analysis and processing to be done in a globally-harmonised manner. This protocol has been curated by multidisciplinary experts across the world 2, and employed in response to outbreaks such as:
Middle Eastern Respiratory Virus Syndrome coronavirus (MERS-CoV) in 2012,
Influenza in 2013,
Ebola virus in 2014,
Monkeypox and MERS-CoV in 2018,
Tick-borne encephalitis virus (TBEV) in 2019 and
SARS-CoV-2 in 2020.
The ISARIC WHO CCP has been central to the swift and cohesive research response to COVID-19. As a free, readily available resource it has been instrumental in the standardised collection of samples and data for the COVID-19 outbreak. This in turn has allowed clinical investigation to progress as quickly as possible. Global generic documents can be accessed here. Countries are also encouraged to develop “localised” instructions and seek local research permissions. The documents pertaining to UK protocols are available here.
Cohort: a cohort of patients are a group of individuals affected by a common factor, such as a disease, treatments or environmental factors.
Cohort study: cohort studies are central to the study of epidemiology and are often used in the fields of medicine, nursing, psychology and social sciences.
Comorbidity: presence of one or more medical conditions in addition to the condition being studied.
Epidemiology: the study and analysis of factors contributing to disease and health outcomes. In this case it may refer to the frequency and pattern of COVID-19 infection, risk factors, super-spreader events and study of specific populations.
Median: the median is defined as the ‘middle’ value of a data set, such that other values are equally likely to be above or below.
Risk factor: a factor that increases an individual’s risk or susceptibility to a disease.
Aim of the study:
To rapidly understand the clinical characteristics of people severely affected by COVID-19. Severely affected, meaning those who need hospital care.
Why is this work important?
This work is essential to appreciate the clinical features of patients that present with COVID-19 and identify risk factors associated with poor outcome. It is only through the understanding of such aspects that public policy can be informed, particularly around shielding of vulnerable groups and planning of resources such as oxygen and ventilator provision.
Who took part?
20,133 hospital in-patients with COVID-19 from 208 acute care hospitals across the UK were enrolled into the study. Clinical data was collected from patients admitted to hospital between 6th February and 19th April 2020. Patient outcomes are described as known on 3rd May 2020, as people admitted on the 19th April need at least 14 days to complete their admission or “declare the nature of their illness”.
The ISARIC WHO CCP-UK is a large ongoing study of patients hospitalised with COVID-19. This study found that the mortality rate was high in those admitted to hospital. Certain risk factors were associated with higher mortality rate such as; increasing age, male sex, and chronic comorbidity, including obesity. This report provides the first clinical insight of hospital patients with COVID-19 in the UK. The data gathered throughout this study will assist decision-making in the management of COVID-19, from patient to nation.
This report acknowledges the 2648 frontline NHS clinical and research staff, volunteer medical students and many researchers, who have worked tirelessly to make this study happen. Thank you to all involved and congratulations from The Science Social.
A note on ‘open access’
Open access journal articles are available to everyone and are not behind a pay wall. This article is freely available to all, if you would like to read the original article click here.
1 Docherty, A. B. et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ369, m1985, doi:10.1136/bmj.m1985 (2020).
2 Dunning, J. W. et al. Open source clinical science for emerging infections. The Lancet Infectious Diseases14, 8-9, doi:10.1016/S1473-3099(13)70327-X (2014).
Thank you to Professor Calum Semple (@tweediechap), an ISARIC investigator and co-author of the original article for permission to write this blog, and for the valuable comments.
All feedback and comments are welcome, get in touch:
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.
“SARS-COV-2 was already spreading in France in late December 2019” – A Scientific Perspective.
A French study has recently made the claim that SARS-CoV-2, the causative agent of COVID-19, was detected in France on December 27th after re-testing samples from patients diagnosed with unknown pneumonias. A single sample, belonging to a French man, tested positive for SARS-CoV-2 DNA multiple times by PCR.
Figure 1: The original paper published in ‘International Journal of Antimicrobial Agents’.
Does this explicitly mean he had COVID-19?
Not necessarily, however, more evidence is required before drawing any final conclusions. The claim is based on a PCR experiment which suggested segments of the SARS-CoV-2 genome were present in this sample. False positives can occur in this type of experiment. The investigators compensate for this by running the PCR twice. Other methods the investigators could have used to further validate this claim include are viral genome sequencing, use of phylogeny to study how closely related this viral genome is to others that the science community have sequenced and finally serology, to detect antibodies that would have been produced by the immune system during infection.
Sequencing is the process of determining the sequence of nucleotides within DNA or RNA. Knowing this can mean the virus can be compared to ‘reference genomes’ of other viruses to see if there is a match. This sequence can also be used to construct phylogenetic trees which show the evolutionary relationships between organisms, including viruses. The more closely related the virus is the more similar it usually is. These methods would show that the virus was present in the sample and also confirm where the virus belonged on the evolutionary tree, allowing scientists to pinpoint whether this virus was closely related to the viruses observed at the beginning of the outbreak.
Finally, serological evidence would prove that infection had occurred. Serological evidence is based on antibodies, a protein produced during the innate immune response to neutralise pathogens. The presence of RNA doesn’t necessarily mean infection (see the recent stir created by RNA being detected in dogs for example), antibody production does as it proves an immune response was mounted. Scientists would require a blood sample from this patient, many different tests can be performed but for SARS-CoV-2 it’s likely a simple colour change test would be used – similar to a pregnancy test(1).
Figure 2: Methods for validating identities of infectious diseases.
So, should we discount the study?
No, we shouldn’t. A result is still a result and knowledge of this is important. However, when information isn’t communicated well, or an incomplete picture is presented a wave of misinformation can occur. It’s important now more than ever to think critically about information and our sources of information. Ultimately, this is what the Science Social is about – communicating science with non-scientists and encouraging critical thinking.
Have any questions about the content covered today? Drop us a message on any of our platforms.
1. Amanat F, Stadlbauer D, Strohmeier S, Nguyen T, Chromikova V, McMahon M, et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. medRxiv [Internet]. 2020 Jan 1;2020.03.17.20037713. Available from: http://medrxiv.org/content/early/2020/04/16/2020.03.17.20037713.abstract
We discussed the latest updates on drug therapies as countermeasures for COVID-19 here. Instead of treating diseases, vaccines have the capacity to prevent them.
No, really what is a vaccine and how do they work?
Like natural infections, vaccines work by initiating a first line immune response, known as the innate immune response. In turn this allows the body to remember the pathogen, preparing the body to defend itself on the pathogens next attack, known as an adaptive immune response 1. Each pathogen (or vaccine) contains unique and specific shapes that the body’s immune system is able to recognise. Once the pathogen is dealt with, the adaptive immune response establishes what we call immunological memory, which is essentially the main goal of vaccination 1.
There isn’t just one type of vaccine either, scientists have found different ways of getting your immune system ready and prepared for infectious diseases.
Two main types of vaccines
Vaccines can be split into two main categories 2:
Live attenuated vaccines
This is when scientists take the causative agent of the disease, i.e. the virus or the bacteria and weaken it so it can no longer cause disease in healthy people. This is not an appropriate vaccination method for those with an immune system that does not work 1,2.
Live attenuated vaccines tend to be produced for viral diseases, as viruses have fewer genes and weakening these pathogens can be achieved more reliably 1.
Examples of Live Attenuated Vaccines used in the UK are as follows:
Measles Mump and Rubella Vaccine
If you are big on your travelling, you may have had the Yellow Fever Vaccine or the oral typhoid vaccination.
These types of vaccines contain either; the whole bacteria or virus that have been “killed”. OR, small elements of the disease-causing agents such as associated proteins or sugars. All of which cannot cause disease, even in those with severely weakened immune systems. The immune response produced by these vaccines aren’t always as powerful as those observed in a live attenuated vaccine, and because of this may require boosters 1,2.
Adjuvants are often added to inactivated vaccines to help boost the immune response and thus make them more protective.
So, an adjuvant is actually an aluminium salt that is added to vaccines to help produce an immune response, such as aluminium hydroxide, aluminium phosphate or potassium aluminium sulphate.
This is not like injecting an aluminium can into your body, by the way. Aluminium is actually a very natural metal found naturally in water, food and the earth itself. The amount used in vaccines is very tiny and is a vital element for these types of vaccines to protect you2.
“Whole killed” vaccines
Some examples of diseases prevented with inactivated “whole killed” vaccines are; poliovirus, hepatitis A, Rabies and Japanese Encephalitis 2.
There are 3 types of subunit vaccines; toxoid, conjugate and recombinant vaccines. All of which essentially take a subunit of the pathogen and turn this into a vaccine 2. When scientists say subunit, they are referring to only a part, or an element of the pathogen as opposed to the whole thing.
Many bacteria release toxins during an infection. Our bodies are able to recognise these toxins and produce an immune response. Therefore, making these a good target for vaccines. Examples of toxoid vaccines are Diptheria, tetanus and pertussis (whooping cough) 2.
The work “conjugate” means connected or joined. Sometimes, the subunit of a pathogen doesn’t elicit a good enough immune response by itself, so the subunit is joined to something else. Quite often the subunit is joined to the tetanus or diphtheria toxoid. Examples of conjugate vaccines are Haemophilus influenzae B, Meningitis C, Pneumococcal and Meningococcal vaccines 2.
These types of vaccines take the genetic code (DNA) from the virus or bacteria that we want to protect ourselves from. In the case of the Hepatitis B vaccine, the DNA is inserted into yeast cells, which are able to produce surface proteins of the pathogen. This is then purified and used as the active part of the vaccine. Examples of recombinant vaccines: Hepatitis B, Human Papilloma Virus and Meningitis B vaccines 2.
Vaccine trials are essential
Like we discussed in our article about drugs, all medicines have to go through a robust clinical trial. This is to ensure that the vaccine is not only safe, but to test whether the vaccine works and provide sufficient protection.
Phase I: a small-scale trial to assess whether the vaccine is safe in health people.
Phase II: more participants are recruited, and the study assess the efficacy of the vaccine, vaccine safety and the immune response is studied.
Phase III: The vaccine is studied under natural disease conditions, hundreds to thousands will be recruited to the study.
If the vaccine retains safety and works well over a defined period of time, the manufacturer of the vaccine is able to apply for a licence to market the product for human use.
Phase IV: The vaccine has been licensed and approved for use, however, data is still collected to monitor adverse effects and to determine the longevity and effectiveness of the vaccine 3,4.
Eradication of disease
In May 1980, the world was declared free of smallpox 5. The last naturally occurring case of this disease was observed in Somalia in 1977 5. Edward Jenner in 1796 observed that those who contracted cowpox, a disease known to be very mild, developed immunity against smallpox 6. This inspired Jenner to prepare a vaccine containing material from cowpox lesions, where he knew “the annihilation of smallpox must be the final result of this practice”. Despite this ground breaking discovery, it took nearly 200 years to eradicate smallpox 5. Smallpox remains the only human infection eradicated by vaccination.
Of course, it is not only humans that are vaccinated against infectious agents, but our pets and our livestock are also vaccinated. Rinderpest is known as the most devastating infectious disease of cattle, associated with a mortality rate more than 70% 7. Rinderpest is a virus belonging to the same virus family as measles. In 1918, the first vaccine was developed in Korea as an inactivated virus. This later got developed into a live attenuated vaccine until 1989 where the first recombinant rinderpest vaccine was developed 7. However, before the recombinant vaccine got to trial, eradication was achieved with the use of Plowright’s live attenuated vaccine 7.
Vaccines will allow us to prevent the disease, protect vulnerable members of our communities through herd immunity and in turn reduce the pressure on healthcare systems.
There is currently no vaccine for any of the known coronaviruses. Despite massive research efforts, it is not expected that a vaccine against SAR-CoV-2 will be available in less than 18 months 8. Keep an eye out for a break down on SARS-CoV-2 vaccines that are going through trial over the next couple of weeks.
1 Vetter, V., Denizer, G., Friedland, L. R., Krishnan, J. & Shapiro, M. Understanding modern-day vaccines: what you need to know. Annals of Medicine50, 110-120, doi:10.1080/07853890.2017.1407035 (2018).
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).
Following on from our recent Q&A, we’ve complied the most recent data available to give you an overview of the statistics. Our first social media fact check! Swipe for our basic breakdown on 📊 age and sex stats, 🩺 incidence of pre-existing health conditions 🏥 and why COVID-19 cases wouldn’t have been misreported as flu.
As always send us your questions, comments and queries ❣️
Since making this infographic more information has come to light! Check out our blog post summarising a research article published in The BMJ here.
We’ve been sent some great questions already and wanted to start by answering those most commonly asked. If you have any questions for us to field, email us and we’ll investigate 🕵🏻 🔍 or comment below! ⬇️
Often during virus outbreaks, conspiracy theories arise which purportedly explain the emergence of the virus. These range from deliberate government release as an agent of population control to Illuminati concocted plagues designed to disrupt our way of life in order to usher in the New World Order. The Covid-19 pandemic is no exception and there has been a wave of conspiracy theories relating to SARS-COV-19, the virus behind Covid-19. Writing in Nature, Kristian G. Andersen, Andrew Rambaut , Ian Lipkin, Edward C. Holmes and Robert F. Garry sought to investigate the origins of SARS-COV-2, not only in order to dispel some of these theories, but also because during a pandemic it’s important to know where the virus came from as this may inform future preventative strategies.
The authors first start by analysing the receptor binding domain (RBD) of the SARS-COV-2 spike protein. This protein is present on the outside of the SARS-COV-2 virus particle and is responsible for the binding of the virus to the receptor ACE2, which is found on the surface of cells. It’s this protein which the virus exploits to enter our cells, and it’s been shown to be very important for coronavirus host range and pathogenicity.
While it’s clear the SARS-COV-2 RBD is able to successfully bind the ACE2 receptor found in human, ferret and other similar species, this interaction is not exactly perfect. In fact, SARS-COV-2 binds with less efficiency than SARS. If a super plague was generated in a lab, computational studies could have been carried out to formulate better binding of ACE2, therefore improving the infectivity of the pathogen. Pretty sloppy work, Illuminati. It’s much more likely that the RBD of SARS-COV-2 evolved to bind a human-like ACE2 and has been acted upon by natural selection. What do I mean by a human-like ACE2? Remember that we share about 98.5% of our DNA with chimps and around 85% with mice, so its highly likely that SARS-COV-2 evolved to infect a similar, but different species, which provided it with some limited ability to infect humans. Once this human transmission was set up natural selection can allow the virus to adjust to humans in order to infect us more efficiently – more on that later.
There’s also good evidence that SARS-COV-2 wasn’t generated in a lab due to the fact it doesn’t appear to have been designed according to other viral “reverse genetics” systems. Reverse genetics systems are what scientists use to produce genetically manipulated viruses in the lab. These techniques employ the use of the virus genetic material which has been probed and packaged through a variety of molecular techniques which allows infectious virus to be generated. The authors make it quite clear that SARS-COV-2 shows no evidence of being generated by the use of these existing virus reverse genetics systems. So, if SARS-COV-2 is naturally occurring, how did it infect humans in the first place and start the whole pandemic off?
The authors provide two hypotheses:
1) The virus arose in animals and, through natural selection, acquired the necessary genetic changes needed to infect humans, whereupon it jumped the species barrier and infected people.
2) The virus jumped from an animal species into humans, whereupon it spread through the human population and, through natural selection, acquired the genetic changes needed to successfully cause a pandemic.
By comparing the genetic material of SARS-COV-2 and other coronaviruses which have been sampled from different species, it has been shown that SARS-COV-2 shares high sequence similarity with those coronaviruses found in bats. The Huanan market in Wuhan is considered to be ground zero for this pandemic and it is known that bats were stored and sold here, in addition to a myriad of other species. It is therefore highly probable that one of these species was host to the progenitor of SARS-COV-2, which then found its way into the human population.
Interestingly, the RBD of SARS-COV-2 is unlike those found in bats but shares high homology with those found in pangolins. Pangolins are an endangered, and very cute, little species of mammal which are the most illegally trafficked animals in the world. Coronaviruses isolated from these creatures exhibit RBDs with high similarity to those found in SARS-COV-2. Pangolins are also thought to have been present at the Huanan market in Wuhan.
Coronaviruses are also known to undergo genetic recombination, in which they swap genetic material. This happens when two different coronaviruses find themselves infecting the same host. It’s therefore highly likely that SARS-COV-2 arose from a recombination event between two coronaviruses, possibly from bats and pangolins, which was then able to jump into humans.
There’s one more feature of SARS-COV-2 that the authors draw attention to: the addition of a polybasic cleavage site which sits between the two subunits of the spike protein. This site is unique to SARS-COV-2 and may result in efficient cleavage by cellular proteases such as furin. This sounds quite complicated. Simply, the virus has evolved a site in the portion of the virus which is responsible for invading our cells which improves its ability to function, therefore making it more infectious.
We see such adaptations in avian influenza all the time – they arise through natural selection when flu spreads through chicken populations. Such adaptations result in the generation of highly pathogenic bird flu strains and are a major public health concern. Mutations of this type which affect the spike protein subunit junction have also been found in nature many times before. These inserted residues also change the structure of the spike protein slightly in a way that the authors hypothesise may help the virus evade the host immune response.
“OK, so where did this genetic change come from? Is it possible for this to happen in the lab? Can it happen in nature?”
Simply, both are possible, but one is less likely. Looking at our two theories it’s entirely possible that this mutation, which likely allows for increased pathogenicity, arose during repeated human to human transmission, similar to what we see in birds with flu. This would mean that, after making the jump from bats/pangolins/unknown species to human, SARS-COV-2 spread through the human populace, acquiring this mutation, and then setting off the chain of events which led to the pandemic. We see this in SARS often, in which the virus jumps from camels to humans and then spreads from human to human for a short period. Crucially SARS has not yet been able to sustain its human-human transmission, whereas SARS-COV-2 has. It’s also possible that this mutation arose in the progenitor to SARS-COV-2 in an animal host. To have arisen this would require sustained transmission between hosts that are in high density and have human-like ACE2 receptors.
Both theories are plausible…
…What isn’t as likely is that the virus gained this adaptation in a laboratory setting. In labs around the world viruses are routinely grown in cell culture. Viruses are introduced to cells in culture, allowed to grow, and eventually harvested. This is known as “passage”. For this mutation to arise in cell culture the virus must have been serially passaged through cells which contain a human-like ACE2 receptor. While these passages take place, the virus is continually evolving, so much so that serial passage in cells eventually leads to viruses getting so good at infecting cells in culture they become worse at infecting whole animals. It’s theoretically possible that the virus could have been serially passaged through an animal, one which contains sufficiently human-like ACE2, however this has never been documented.
It is very unlikely that SARS-COV-2 originated in a laboratory setting
…and it doesn’t exhibit the genetic fingerprints we’d expect a genetically modified super plague to exhibit. Unfortunately, at the moment all we can do is theorise about its origins until the exact host, or progenitor virus, is found. There are a staggering number of viruses present in nature which we simply haven’t discovered yet (think of a tip of the iceberg kind of thing) which are currently quietly circulating in animals, and possibly humans, throughout the world. The conditions which we saw at the Huanan market in Wuhan in which various different exotic animals are stacked, live and dead, in cages in close proximity to each other, and humans, makes the perfect melting pot for these pandemics to arise. Furthermore, as humans clear more habitat, and as global temperature rise allowing vector species such as mosquitos and midges to extend into higher latitudes, it’s a matter of time until this happens again. While this pandemic is ongoing, the next one in line is lurking out there and it’s vitally important that we learn what we can from SARS-COV-2 so that we are prepared when it finally emerges.
Coronavirus: A natural phenomenon or a man-made weapon? Read a lay summary of @NatureMedicine article: The proximal origin of SARS-CoV-2 by @K_G_Andersen, @arambaut and @edwardcholmes and co. Written by @jordandoesflu with @thescisocial #covid19 #sarscov2 #mythbusters https://thesciencesocial694680041.wordpress.com/?p=104