“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.
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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).
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.
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