CORONAVIRUS: THE WHOLE STORY

By Yadukrish Karthikeyan

Figure 1: Coronavirus Illustration ^[1]

Introduction

The COVID-19 pandemic has changed the world, and will likely continue to for the foreseeable future. This report explores the virus that caused this commotion, how and where the virus originated, and how the human race is predicted to finally overcome it.

Part I: The Virus

An Introduction To The Virus

A common misconception is that the pandemic is caused by a virus called COVID-19. This is incorrect. Whilst the name of the pandemic is COVID-19, the virus that caused this pandemic is known as the SARS-CoV-2 virus. The name is derived from Severe Acute Respiratory Syndrome (SARS), CoV meaning coronavirus, and 2 due to it being the second virus of its kind. The name COVID-19 comes from COVID which refers to a coronavirus, and 19 due to 2019 being the year the virus was first identified.

Origins of the Virus

The SARS-CoV-2 virus was first detected in the Chinese Province of Wuhan^[2]. Currently, scientists have found that the genome of the virus (made up of 30,000 nucleotides) is 96% similar to the bat coronavirus and 91% similar to the pangolin coronavirus. This indicates that the coronavirus may have originated from pangolins, before being transmitted to bats and, finally, into a human, where the virus spread throughout the world. However, this theory is challenged when factoring the similarities between the spike proteins of the viruses. Once again, the spike proteins (S-proteins) are 96% similar to the bat coronavirus but are 99% similar to the pangolin coronavirus^[3][4].

Scientists theorise that the genome comes from a bat, but the S-proteins are mainly from the pangolin coronavirus. This theory is highly plausible, as ‘wet markets’, where the SARS-CoV-2 virus is thought to have originated, could allow for this to happen. In these markets, which are mainly found in China and South-East Asia, animals are bought alive and are slaughtered on-demand by the purchaser. There, the virus in a pangolin could have mutated to infect bats. In an environment such as this, an antigenic shift could have occurred, where the genomes of both the pangolin and bat viruses are mixed together in the same cell, creating a new coronavirus with its own unique genetic coding. This new virus could have then spread to a human, which was then transmitted to others ^[3]. However, this is merely a theory and is subject to change as knowledge of the SARS-CoV-2 virus expands.

The Virus: Structure and Function

The name ‘Coronavirus’ has a strong correlation with the structure of the pathogen which is likened to that of a crown due to its S-proteins.

The RNA is encased in a lipid membrane with antigens on the outer surface. The RNA is the genetic material of the virus and plays a major role in the replication process that allows the pathogen to spread throughout a host’s body. After entering the cells by endocytosis, the RNA is taken to the ribosomes where it codes for the production of more viruses. These viral components are then assembled and leave the host cell by exocytosis. There are two types of these antigens on the SARS-CoV-2 virus: the S-Proteins and M-Proteins. These antigens are slotted in by holes in the membrane. The S-proteins are crucial in the virus’ function, as they bind to the Angiotensin-Converting Enzyme 2 (ACE2) receptors on the host cells. This is essential in order for the RNA to enter the cell.

Figure 2: The structure of SARS-CoV-2 ^[5]

How SARS-CoV-2 Works

Once the virus enters the body, either through the nose, mouth or eyes, the pathogen enters the lungs through the trachea. Once in the lungs, the virus enters the blood through pneumocytes, the cells in the lungs which allow the diffusion of oxygen into the bloodstream. When the coronavirus enters the cells, ribosomes use the viral RNA to make new copies of the parts of the virus, which are then put together and expelled from the pneumocyte. This process happens thousands of times to increase the number of viruses in the host. After this, the virus travels through the blood and infects more cells, resulting in the host’s body becoming overridden by SARS-CoV-2 ^[6].

How The Human Body Responds

Figure 3: A flow chart of the body’s response to SARS-CoV-2

Elaboration:

* – Neutrophils are the most abundant white blood cells in the body and engulf pathogens. Macrophages, on the other hand, use their long ‘arms’ to bring their enemies close to them before swallowing them whole. The third type of cells is the natural killer cell. These cells do not require activation and release cytotoxins that are highly effective against cells infected with viruses ^[7].

** – ACE2 receptors are the receptors to which the antigens of the SARS-CoV-2 virus bind to. Once attached, the virus is anchored to the cell, and can release its viral RNA into the host cell. These ACE2 receptors are found in many parts of the body, such as the lungs, the heart, blood vessels etc. as well as in epithelial cells, which make up many protective barriers, like mucus, the skin and the urinary tract ^[8].

*** – Ribosomes synthesise RNA into cellular components. This is where the viral RNA goes to start the production of viral components (antigens, membranes etc.) These ribosomes produce almost all viruses that go on to infect other host cells ^[9].

**** – Signalling is when an antibody alerts the immune system and initiates the immune response at the site of initial infection. Interference refers to when antibodies block all of the antigens on a virus, blocking it from binding to a host cell. Agglutination is the final use of antibodies, by which viruses are clumped together so they are easier to be engulfed and destroyed by the cells of the immune system ^[10].

As well as having a cellular approach to the virus, the body also has physical responses. A fever happens when the body heats itself up in order to help the immune system work more efficiently. The increased heat of 3-4°C allows it to work at optimum efficiency as well as making it harder for the viruses to reproduce, slowing down the virus’ spread through the body. There is also an increase in mucus production in order to allow quicker destruction of foreign bodies as mucus has a high amount of antibodies and immune cells. This excessive mucosal production, however, has negative effects (such as pneumonia) and may increase the number of respiratory droplets in your system, making it easier to spread the virus.

 

Part II: The Solution

What is the Ultimate Solution?

Although it may seem that the end of the coronavirus’ reign is near as cases and deaths around the world drop every day, the true solution will be found only when a vaccine is released for the SARS-CoV-2 virus. Eradication of this virus will occur when an effective vaccine is made, distributed and administered to people globally.

Vaccines: How Do They Work?

According to the Merriam-Webster Dictionary, a vaccine is the “preparation of killed microorganisms, living attenuated organisms, or living fully virulent organisms that are administered to produce or artificially increase immunity to a particular disease ^[11]”. There are four main types of vaccines: attenuated, inactivated, toxoid and biosynthetic vaccines.

An attenuated vaccine, as the name suggests, uses a weakened form of the virus or bacteria. Examples of these vaccines are the MMR (Measles, Mumps and Rubella) Vaccine and the Varicella (Chickenpox) Vaccine.

The second type is inactivated vaccines that introduce dead remains of the pathogen into the body. These remains usually include the antigens of the virus, allowing the body to create antibodies in advance of the real infection. An example of this type of vaccine is the Pertussis (Whooping Cough) vaccine.

Toxoid vaccines involve the use of the toxins and chemicals made by the virus in order to sensitise the body to the threat. These protect the body from harmful effects of the virus, but not the virus itself. Examples of these are the Tetanus vaccine and the Diphtheria vaccine.

Finally, biosynthetic vaccines use man-made chemicals and materials that resemble the virus, deceiving the body into thinking that it is fighting the real pathogen. An example of this is the Hepatitis B vaccine.

After the vaccine is administered, the body activates the immune response. This allows the body to develop memory cells with the specific antibodies to combat the real pathogen. In the case of a secondary infection, the body is primed to neutralise the threat by mounting a secondary response which is much faster and more effective than the primary response.

Alternative Solutions

Alternative treatment options for COVID-19 include, but are not limited to: antivirals, convalescent plasma therapy and symptomatic supportive treatment (SST).

Antivirals generally refer to pills that inhibit replication of viruses by blocking viral polymerase.

Plasma therapy is a treatment in which the plasma of a person who has had SARS-CoV-2 is injected into a person with coronavirus, in order to supply the patient with antibodies that the plasma donor had made during their time with SARS-CoV-2. This treatment has been used in critical conditions around the world, with success. However, Plasma Therapy cannot be a long-term option, as it is a treatment, and not a way to eventually eradicate the virus.

SST has been used for centuries and can be used against the SARS-CoV-2 virus. SST, as the name suggests, treats the symptoms of an illness but not the cause. This could refer to techniques as simple as sponging to cool down a patient with a fever or taking an analgesic to reduce pain. However, like plasma therapy, this is not a long-term solution, as it does not limit or eradicate the spread of the pathogen.

Current Developments

Treatments for the SARS-CoV-2 Virus are developing every day, led by pharmaceutical companies all around the world, each with a different type of treatment. The following include the leading contributors in each of the treatment sectors (vaccines, treatments, infection prevention, etc.)

Oxford University & AstraZeneca – Vaccine

Product Name: AZD1222 (ChAdOx1 nCoV-19)

Stage: Phase III Trials (as of August 28 2020)

Product Type: Vaccine

AstraZeneca’s partnership with Oxford University has given people high hopes, and with good reason. Currently, the AZD1222 vaccine is in trials in Brazil and has been met with high levels of success. The UK has ordered 100 million doses of the vaccine after AstraZeneca’s trials around the world showed that the vaccine did lead to an immune response and the body began making antibodies for the SARS-CoV-2 virus. AZD1222 uses a replication-deficient chimpanzee adenovirus (Cold Virus) with SARS-CoV-2 spike proteins to familiarise the host’s body with the pathogen ^[12]. AstraZeneca’s vaccine has shown a 90% efficacy rate in phase III trials.

Gilead Sciences – Treatment

Product Name: Remdesivir

Stage: Phase III Trials (as of February 26 2020)

Product Type: Treatment

Remdesivir caught traction around the world after it was given emergency use authorisation. This means that it can be used in hospitals and treatment centres if the usage is warranted. Remdesivir is administered via an injection, as opposed to a pill or tablet. Although Gilead Science’s treatment has been successful in clinical trials and looks like a plausible long-term solution, it has been found that Remdesivir has little to no effect after the autoimmune response is triggered. Therefore, for the treatment to be effective, one would need to take Remdesivir in the early stages of the infection. This medication also did not reduce the death rate of the SARS-CoV-2 virus. Again, treatments simply negate the effects of a pathogen, and so do little against minimising the initial effects of the virus ^[12].

Regeneron Pharmaceuticals – Treatment

Product Name: REGN-CoV2

Stage: Phase III Prevention Trials (as of 14 September 2020)

Product Type: Treatment

Regeneron Pharmaceuticals has worked with the National Institute of Allergy and Infectious Diseases (NIAID) to develop REGN-CoV2, an Antibody ‘Cocktail.’ These ‘cocktails’ essentially provide the host with the monoclonal antibodies (antibodies that are cloned versions of a parent cell’s antibodies) it needs to fight against the SARS-CoV-2 virus, ensuring that if and when the host is infected, they are safe and protected. Although Regeneron has not had as much recognition as AstraZeneca or Gilead Sciences, their product is still viable as a long-term solution to the COVID-19 Pandemic ^[12].

Along with these three leaders in their fields, countless other companies are attempting to produce a solution for this global pandemic, including big names such as Pfizer and GlaxoSmithKline. Below is a list of these companies, their product types and the stages of their trials. The first 4 vaccines in this list have received clinical approval. However, the clinical use and phase III trials have been overlapped in order to expedite the process due to the necessity for a vaccine.

• Moderna Pharmaceuticals / NIAID – RNA Vaccine: Phase III Trials
• Pfizer / BioNTech – RNA Vaccine: Phase III Trials
• AstraZeneca / Oxford University – Replication-Deficient Live Vaccine: Phase III Trials
• Gamaleya Research Institute – Viral Vector (non-replicating): Phase III Trials
• Johnson & Johnson – Replication-Deficient Live Vaccine: Phase II Trials
• NovaVax – Recombinant-Subunit-Adjuvanted Protein Vaccine: Phase II Trials
• Sanofi/GlaxoSmithKline – TBD – Preclinical ^[13]

Pfizer and BioNTech’s vaccine is very unique, due to the fact that it uses messenger RNA (mRNA), which is a synthetic version of the viral RNA. This is very new technology and is the first of its kind; no vaccines have been made using this method before. This vaccine is soon to be deployed in countries such as the UK ^[14], following the release of its trial results showing 95% efficacy. However, like all vaccines being made for COVID-19, the vaccine-making process has been sped up drastically, raising concerns about the longevity of their protection and possible side effects.

A recent study has shown that steroids such as Dexamethasone improve the recovery of patients with COVID-19, and that this can be used in certain situations. The steroid has also been seen in the Oxford RECOVERY Trial as lowering the death rate of patients that are in intensive care or require oxygen, in comparison to a placebo. Dexamethasone works by dampening the body’s overreactions to infection (autoimmune response) ^[15].

 

Concluding Thoughts

In conclusion, the SARS-CoV-2 virus is unique in many ways, creating a pandemic truly out of proportion and our control. Although total eradication is the best-case scenario, this is unlikely due to the existence of alternate animal hosts (bats, pangolins, etc.) which can harbour and further spread the virus. This is the case with influenza, another virus with alternate hosts. On the contrary, smallpox, which does not have alternate hosts, has been eradicated, showing that SARS-CoV-2 also has a chance at being eradicated. I believe that effective vaccinations combined with reducing transmission through protocols such as social distancing is the only foreseeable way in which the pandemic can end.

By Yadukrish Karthikeyan

 

References

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6. Goulding, John. Virus Replication. British Society of Immunology. https://www.immunology.org/public-information/bitesized-immunology/pathogens-and-disease/virus-replication.
7. Nall, Rachel. What to know about white blood cells. Medical News Today. Jan 9. 2020, https://www.medicalnewstoday.com/articles/327446.
8. Sriram, Krishna et al. What is the ACE2 receptor, how is it connected to coronavirus and why might it be key to treating COVID-19? The Conversation. May 14. 2020, theconversation.com/what-is-the-ace2-receptor-how-is-it-connected-to-coronavirus.
9. Ludwig-Maximilians-Universität München. COVID-19: Viral shutdown of protein synthesis. Science Daily. July 17. 2020, https://www.sciencedaily.com/releases/2020/07/200717140738.htm.
10. Forthal, Donald. Functions of Antibodies. National Centre for Biotechnology Information. Aug 15. 2014, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159104/.
11. Merriam-Webster Dictionary. Vaccine, Merriam-Webster Dictionary, https://www.merriam-webster.com/dictionary/vaccine. Accessed 7 December 2020.
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15. Chief Investigators of the RECOVERY Trial on Dexamethasone. Low-cost Dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of COVID-19. University of Oxford RECOVERY Trial. 16 Jun. 2020, https://www.recoverytrial.net/news/low-cost-dexamethasone-reduces-death-by-up-to-one-third-in-hospitalised-patients-with-severe-respiratory-complications-of-covid-19

About the Author

Yadukrish Karthikeyan is a 14 year old boy with a passion for Biology. Studying at the Judd School in Tonbridge, Yadukrish is a member of the Mensa High IQ Society, and has written multiple articles for the Mensa Teen SIG Magazines. With a father in the medical world, Yadukrish has always been curious  about the world of biology, and has constantly been fascinated by the diversity it brings.