Friday 3 April 2020

COVID-19

The beastie of Doom

Introduction
This post is a brief introduction to some aspects of the coronavirus. Clearly, within the limitation of the blogging format, the topic under consideration can only dealt with in a superficial manner: this is not a learned scientific treatise.

The pathogen responsible for the disease COVID-19 (as stated by the World Health Organisation) is designated as a severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2). This is quite a mouthful of nomenclature but entirely warranted considering the mayhem and chaos the virus is currently causing. The genome of SAR-CoV-2 has been sequenced and the virus has been classified as a betacorona virus with filial affinity to the virus responsible for severe respiratory syndrome (SARS). The virus also has a genetic affiliation to several bat coronaviruses. This relationship has led some workers to consider that a bat coronavirus is ultimately responsible for the outbreak. It is envisaged, therefore, that an initial mutation in the bat virus allowed the virus to leap the species barrier thus enabling the infection of a human host.

The virus was first detected in late December 2019 as the cause of a cluster of pneumonia infections in patients from Wuhan city, China. The disease spread quickly throughout China and soon thereafter became disseminated across the globe. SAR-CoV-2 is mainly spread by nasal droplets expelled when infected individuals cough and sneeze. Thus individuals coming in contact with airborne viral particles or viral particles having settled on surfaces can become infected. The time of contact to the expression of symptoms varies between patients but a mean incubation period of 4 days has been reported.

The clinical presentation of the condition is variable in regard to symptoms and severity. The majority of individuals appear to have relatively mild symptoms (about 80%) and severe illness is more prevalent in the elderly and those with already underlying health problems such as pulmonary and cardiac disease.

In general, the symptoms can be described as ‘flu-like’. Thus patients may complain of a dry cough, fever, aching muscles, and fatigue. The most serious manifestation of the condition is pneumonia. The overall fatality rate has been estimated at about 2.3% however, a high level of variance between countries has been reported. The reason for the mortality variance is complex and often poorly understood. Countries with an ageing population (eg Italy) have experienced relatively high death rates of 7%. Indeed it is suspected that reported death rates are inflated as a consequence of ascertainment bias.

With that said, let's have a look at the virus itself.

First off, I’ll not get bogged down with scientific semantics/pedantics concerning the moot point whether viral particles actually constitute life.

Coronaviruses, unlike the vast majority of organisms, do not rely on DNA for genome replication. Instead, they utilise a related molecule called RNA, in a single strand format. The virus is characteristically globular in structure and sports a series of protein protrusions on the surface. These ‘spiky’ projections give the virus its name as corona translates to ‘crown’ in Latin. Specific viral proteins present on the spikes seek out and attach to specific and complementary receptor proteins on the host cell. The ACE2 receptors are uniquely present on cells that form the lower and upper respiratory tract and this ‘key and lock’ association facilitates viral entry into the cell. Once ensconced, the virus, like all viral particles, uses its limited genome to hijack the host cell's protein and nucleic acid making apparatus. In this way, numerous viral particles are formed and assembled within the host cell. Once the assembly has been completed, the newly manufactured viral particles are released and ready to infect new cells within the host or expelled into an awaiting and expectant outside environment: thus disseminated the infection cycle continues anew.

A particular characteristic of RNA viruses is their high mutation rate as they lack the proofreading capacity and necessary nucleic acid repair mechanisms of higher organisms and even DNA based viruses. This is a headache for researchers hoping to produce an effective vaccine as new mutations may circumvent and hence negate a targeted vaccine.

The US, as are other nations, are currently undertaking trials to test novel vaccines. The introduction of a new vaccine tends to be exceedingly and excruciatingly slow due to the painstaking protocol inherent in the introduction of any new therapeutic agent. This is crucially important as not only the efficacy of the agent need to be evaluated but also the risk of undesirable side effects requires assessment. Even if a vaccine proves promising, general availability and widespread distribution are unlikely to occur for at least a year. Unlike other viral vaccines, the vaccine currently under investigation does not utilise a deactivated or attenuated virus particle. Instead, the vaccine is an artificial laboratory constructed piece of messenger RNA (mRNA). Messenger RNA is a crucial intermediary in the production of proteins. The presence of this particular mRNA induces cells to manufacture a protein found on the outer surface of the virus and the presence of this protein stimulates the host immune system to manufacture a repertoire of antibodies. These antibodies are expected to attach to the outer coat of the virus, if encountered, thereby inducing the host's immune machinery to lock on and neutralise this grievous offender. Well, that’s the theory at least, whether this works in practice awaits further elucidation and research.

A different approach is being considered and applied. There are a number of drugs, already evaluated, that have been shown to induce a viral limiting response, either in prophylaxis or during active infection. These drugs have the advantage that they have already been evaluated for efficacy and side effects and thus they can be introduced after limited evaluation. The downside: there are a number of drugs of this ilk that need to be specifically assessed for SAR-CoV-2. This will take a little time but because of the number of agencies working on the issue, I’m sure the research can be fast-tracked. That said, unless we find a ‘wonder’ viral agent, the results are unlikely to be as effective as a specific vaccine.

Enough science for now as I’ve just overrun the critical 1,000-word limit for a blog. Unwritten as the rule may be, it is one that the prudent blogger must adhere to, otherwise, astute readers will bugger off to more succinct pastures.

However, I’m tempted to continue writing upon the fertile field of COVID-19. There is much to cover, such as social impact, epidemiology, etc, etc. If readers would like me to wax lyrical on other aspects of the disease, I’m more than willing to comply/apply. Tis good for my mental health, apparently. Just let me know in the comments. Arse.









6 comments:

  1. Here in England, the windbags in Westminster & Wormtongues in Whitehall are starting to yammer on about testing. They seem to be working hard at understanding something called cyants - late to the party, as usual, but nobody is really explaining the nature of the tests.

    I know there are 'antigen' tests to identify existence of the infection & there are 'antibody' tests to see if the subject has had the disease, but how accurate are they? Presumably there are different versions of each test, probably from different sources, what where are the false positive & false negative figures? And how long between test & result? Does it involve a Petri dish?

    I am reading about anonymous firms supposedly producing wonder tests that give a result in minutes, but same goes.

    1000 or more words on that would be great.

    Cheers,

    DevonshireDozer.

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    1. The test I'm familiar with is a PCR test for the viral RNA. Our lab staff was initially considered to be able to take part in testing. However, the powers that be decided to centralise testing in Auckland. Thus yours truly is likely to be employed as an orderly. Nothing wrong in that. I would like to be of use than no use at all. I could muster up a post on the various testing strategies though.

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  2. Your excellent piece above is most welcome. Further such articles with such lucid, non judgmental detail most welcome and refreshing. Thank you.

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  3. Flaxen, good post but The virus was first detected in late December 2020 - surely 2019

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    Replies
    1. Whoops. Have corrected this manifest error.

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  4. you really did great work lets check mine too
    https://knowhubs.blogspot.com/2020/04/covid-19-stand-for-coronavirus-disease_7.html

    ReplyDelete