COVID-19: Coronavirus and its Origins

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I don’t normally start an article with a string of seemingly random characters. You could be forgiven for thinking that one of our cats has walked over the keyboard! However, this isn’t just a random collection of letters as it is indeed a section of DNA sequence from the newly discovered Wuhan Coronavirus COVID-19. As of January 4th, it has infected 20,000 people and killed 467 of them. Coronaviruses (or CoVs) are a family of viruses that target the respiratory system. They were first discovered in the 1960’s. Most people will have already been infected with a different type of coronavirus during their lifetimes as they are a frequent cause of the common cold. Its name comes from the Latin word corona (which means ‘crown’), because of the spiky fringe that encircles these viruses. These spikes are protein spikes (or ‘peplomers’ as seen below) that are essential to binding on host cells.

Technology allows us to describe our present foe in absolute detail as scientists share complete DNA sequences (called a genome) of our new Coronavirus COVID-19 taken from many different patients over the last month. This is coordinated through GISAID (Global Initiative on Sharing All Influenza Data) which was established in 2008. This was established because of lessons learned from bird flu (H5N1) in 2006 due to the hesitancy by affected countries to share their information. These full genomes are crucial so we can design and evaluate diagnostic tests, to track and trace the ongoing outbreak and to identify how it might be stopped. So, what are coronaviruses and what have we learned?

Coronaviruse COVID-19 and Mutation?

CoVs carry their genetic information as RNA and they have the longest genome of any RNA-based virus – a single strand of nucleic acid roughly 26,000 to 32,000 bases long. Human DNA, for the purposes of comparison, has roughly 3 billion bases! RNA and DNA are quite similar in that they each use four chemical bases. DNA uses adenine, thymine, cytosine and guanine (or A, T, C and G) but RNA replaces thymine with uracil (or U). I am explaining this so you can now understand the sequence at the top of the page and the rest of the article! Pairs of these bases (called nucleotides) form the “rungs” of our twisted, ladder-shaped DNA and RNA molecules. Inside our own cells one of the jobs of our RNA is to read the instructions provided by DNA and basically act as a photocopier, and this is the process that a virus will hijack with its own RNA.

Viruses exploit our cellular machinery in many ways, but in almost all cases, the virus tricks the cell into treating the virus’s RNA as its own and transcribing and/or translating it. What is interesting is that RNA is less stable and more prone to mutation than DNA. RNA viruses generally change and evolve quickly. This sometimes allows RNA viruses to jump from species to species (this is called ‘zoonosis’). The notable recent examples include the avian flu and swine flu, which jumped to humans from birds and pigs, respectively. This is exactly what the Coronavirus COVID-19 has done.

Coronaviruses and their Relationships with other Species

CoVs are abundant and infect many species including bats, cats, and birds but there are only seven types that infect us, including the new CoV discovered in Wuhan which science is referring to as COVID-19. Four CoVs (229E, NL63, OC43, and KHU1) are very common and cause mild to moderate respiratory infections, like the common cold. Two types, Severe Acute Respiratory Syndrome coronavirus (SARS) and Middle East Respiratory Syndrome coronavirus (MERS), can cause serious respiratory infections. The World Health Organisation(WHO) estimated the fatality rate of SARS at 14% and MERS at 34%. COVID-19 appears to closely be related to SARS and but statistics so far indicate the mortality rate is slightly lower. If you are interested to learn more about how COVID-19 spreads and disseminates in the general population feel free to read an article I wrote last year. This describes how coughs and spread so effectively.

Severe Acute Respiratory Syndrome (SARS) was discovered in China in 2002. The virus that causes SARS quickly spread to more than two dozen countries before it was controlled and nearly 8,100 people became infected causing 774 deaths. Since 2004, no cases of SARS have been reported in the entire world. Middle East respiratory syndrome (or MERS) was discovered in 2012. It has since infected nearly 2,500 people and all cases have been linked to travel to or residence in and near the Arabian Peninsula. SARS is thought to have evolved and passed to humans from bats, via civet cats as an intermediary host species! As a matter of interest, the SARS CoV only differed from one CoV found in civet cats by 10 nucleotides which is why scientists were able to make a connection. If you remember CoVs usually have 26,000 to 32,000 bases long so this is virtually identical. MERS it would appear possibly jumped from bats via camels as an intermediary species. No one really knows where COVID-19 came from, but it is clear that it made the leap from animals in Wuhan, a city of 11 million, late last year.

The Coronavirus COVID-19 is Closely Related to SARS

In general, the longer a virus circulates in a human population, the more time mutations develop. Currently the genomes of COVID-19 that have been sequenced only differ by a very small amount. They differ by only seven nucleotides. This small difference in nucleotides indicates that COVID-19 jumped into humans very recently. But it remains a mystery which animal spread the virus to humans. At this point researchers have found that it is most closely related to other CoVs found in bats with a difference of 1100 nucleotides. According to a team at Wuhan Institute of Virology, the new COVID-19’s sequence is 96.2% similar to a bat CoV and has a 79.5% similarity to SARS. In fact, they estimate that COVID-19 shared a common ancestry with SARS anywhere between 25-60 years ago. Scientists currently suspect that there is an unidentified intermediary host species involved in transmission just like civet cats and camels for SARS and MERS. This is supported by strong evidence that suggests that a marketplace in Wuhan (called Huanan) played an early role in spreading 2019-nCoV. Of the 585 samples tested form the Huanan marketplace, 33 were positive for 2019-nCoV and all were in the huge market’s western portion, which is where wildlife was sold. So how infective and serious is COVID-19?

How Serious is Coronavirus 2019-nCoV?

Most patients who have been infected with COVID-19 have mild symptoms and a relatively good prognosis. So far, only a few patients with COVID-19 have developed severe pneumonia, pulmonary oedema or ARDS (acute respiratory distress syndrome) have died. The Lancet medical journal published the first study reviewing some of the first patients admitted to hospital in Wuhan. Of these 99 patients, 49 (49%) patients had a history of exposure to the Huanan seafood market. Among them, there were 47 patients with long-term exposure history, most of whom were salesmen or market managers, and two patients with short-term exposure history, who were shoppers. None of these 99 patients were medical staff. By the end of Jan 25th, 31 (31%) patients had been discharged and 11 (11%) patients had died; all other patients were still in hospital. Of the 11 patients who died most were male and over the age of 55 years old with pre-existing conditions such as cardiovascular diseases and diabetes. 40 had a weak heart or damaged blood vessels due to conditions including heart disease, heart failure and stroke and a further 12 patients had diabetes. This probably contributed to a mortality rate in greater than current rates suggest. As of January 4^{th, COVID-19} has infected 20,000 people and killed 467 of them (mortality rate of 2.3%).