In December 2019, the world got to know that a novel human coronavirus had begun to spread undetected among the population of Wuhan, a large city in the Hubei province of China. Since then, this novel coronavirus has spread to several countries beyond Asia. The World Health Organisation (WHO), after assessing the uncontrollable spread, declared this as a pandemic.
As of March 26, 2020, this novel coronavirus, termed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has been responsible for 487,000 infections globally – causing 22,000 deaths. In Italy, the U.S. and Iran, the virus has affected 74,280, 65,400 and 29,406 people respectively, and has claimed 7,500, 940 and 2,230 deaths respectively in these three countries. SARS-CoV-2 virus causes Coronavirus Disease 2019 (COVID-19).
Coronaviruses, in general, are a family of viruses that affect the respiratory system. Most target animals, but a few can also affect humans. There are only two coronaviruses to date that have previously caused global outbreaks. The first was the coronavirus of 2002 that causes severe acute respiratory syndrome (SARS). This outbreak also started in China but died off in 2003. The epidemic predominantly affected mainland China and Hong Kong.
The second was the MERS (Middle East Respiratory Syndrome) coronavirus, which started in Saudi Arabia in 2012. At the end of January 2020 a total of 2519 confirmed cases of MERS, including 866 deaths (case-fatality rate of 34.3 percent), were reported globally.
What is the origin of this novel coronavirus?
Humans become infected with a coronavirus via contact with an infected animal. Some of the most common animal carriers are bats, although they do not typically transmit coronaviruses directly to humans. The transmission usually occurs via an ‘intermediary’ animal, which would commonly be a domestic animal.
The SARS coronavirus infects humans via civet cats, while the MERS virus uses camels as the ‘intermediary’. In the case of SARS-CoV-2, the initial reports tied the outbreak to a seafood market in Wuhan. Consequently, the health authorities closed down the market on January 1, 2020.
However, thorough assessments afterward have suggested that this seafood market was unlikely to be the sole source of the outbreak, since some of the infected people with the virus had either never visited the market or had not been visiting the market on a regular basis. Health authorities and epidemiologists have since not been able to determine the exact source or reservoir of the virus.
How is the virus transmitted?
While animals are likely to be the origin of the new coronavirus, transmission from person to person can also occur. Researchers are still studying the exact mode of the human-to-human transmission.
What we do know, however, is that similar to other coronaviruses, transmission is via the respiratory route (i.e. through the nose and lung airways) and can infect another person via droplets. More research is nevertheless needed to further comprehend this transmission mode to others.
In Wuhan, the epicentre of the outbreak, some infections occurred from exposure to a source that was most likely an infected animal. This was then followed by human-to-human transmission. Current information indicates that mildly-infected individuals, say with just a mild cough and not feeling ill, can shed the virus – and severely infected individuals also shed the virus; but the more severe your symptoms, the more likely you will be to transmit the disease.
Although the World Health Organisation (WHO) estimates that the novel coronavirus’s incubation period could last anywhere between 1 and 14 days, research data available strongly indicate that the incubation period for SARS-CoV-2 is probably between 5 and 6 days; i.e. once infected, the virus likely takes about 5 – 6 days to give rise. Nevertheless, the 14-day window gives ample time to see symptoms in infected individuals.
How does the new coronavirus differ from other viruses?
Chinese researchers have been able to identify the DNA structure of the novel coronavirus by using state-of-the-art genome sequencing tools. SARS-CoV-2 has 88 percent genetic similarity to two bat coronaviruses known as Bat-SL-CoV-ZC45 and Bat-SL-CoV-ZXC21. The same study shows that SARS-CoV-2 has 79 percent genetic to that of the SARS coronavirus discovered in 2003, and about 50 percent similarity to that of MERS coronavirus.
Another recent study by a different Chinese team has suggested that pangolins may the initial transmitters of SARS-CoV-2, since their DNA sequence was approximately 99 percent similar to bats. However, other health scientists have downplayed this assertion due to inconclusive data.
For the past three months since the outbreak, scientists have made a lot of educated guesses about the COVID-19 – primarily because the virus is new and there is no data currently to inform us about its characteristics, even though some beliefs have been hyped by mere anecdotes.
What we know now
One of the strongest hopes we have, however, is that by their nature individual coronaviruses can be easily destroyed. The novel coronavirus particle consists of a small set of genes, encapsulated by fatty lipid bi-layer molecules – and these lipid envelopes are easily destroyed by at least 20 seconds of thorough hand-washing with soap under running water.
The lipid shells are also vulnerable to the elements; research has shown that the new coronavirus, SARS-CoV-2, cannot survive more than a day on cardboard, or more than three days on plastic and steel. It goes without saying that the coronaviruses need bodies to survive longer. The skin is an ideal ‘bed’ for SARS-CoV-2!
There is still so much to learn about coronaviruses. One reason is the fact that only a few virologists and other scientists found it interesting to actively research on coronaviruses in the early years, because they figured it is a “non-essential” field to human health – the numbers only ballooned after the SARS epidemic of 2003. With the emergence of SARS-CoV-2 as the viral cause of COVID-19 disease, it is hoped scientists will not repeat that mistake.
We need to bear in mind that SARS-CoV-2 is not the same as the flu virus, even though the two can have some overlapping symptoms after infection. SARS-CoV-2 infections may come with distinct symptoms, spreads faster, and kills more readily. The coronavirus family, includes four members – OC43, HKU1, NL63, and 229E – which have been designated as flu-like members, and cause a third of the common colds known to man.
The other two members – MERS and SARS-CoV – both cause a far more severe disease. The question is: why has SARS-CoV-2, the seventh coronavirus, the one to go pandemic? Suddenly, the “non-essential coronavirus”, that scientists knew arguably very little about has become a matter of international concern.
The coronavirus has a spiked-ball structure, and this has largely contributed to its success. The spikes recognize and stick to the ACE-2 receptor on the cell surface. This is the first step to an infection. In the case of SARS-CoV-2, the nature of the spikes allows it to stick more strongly to ACE-2 than SARS-CoV – and this could be crucial for human-to-human transmission. In general terms, the stronger the affinity, the tighter the bond, the less virus needed to initiate an infection.
Despite its animal origins, the novel coronavirus, SARS-CoV-2, seems very effective at infecting humans. The closest wild-type relative of SARS-CoV-2 is found in bats, which suggests it probably originated in a bat before directly or indirectly infecting humans through another species. As stated earlier, another coronavirus discovered in pangolins also resembles SARS-CoV-2, but only in a small section of the spike which recognise ACE-2.
The overall similarities between these two viruses are minimal, making pangolins highly unlikely to be the original source of SARS-CoV-2. When SARS-CoV was initially discovered, it took a while for the appropriate mutations to fully recognise ACE-2. In contrast, SARS-CoV-2 recognised the ACE-2 receptor from day-one. It goes without saying that SARS-CoV-2 had already adapted to being a ‘human receptor-recognising virus’.
Another adaptive feature of coronavirus is the two connected halves on the spike protein which bind cellular receptors and mediates membrane fusion. The virus can only enter a host cell when the spike is activated after N- and the C-terminal domains of the two connected halves are separated. In SARS-CoV, this separation occurs with some appreciable difficulty. But in SARS-CoV-2, an enzyme called furin made by human cells can easily cut the terminals which connect the two halves; undoubtedly, one of the unusual phenomena present in this new coronavirus.
Most respiratory viruses tend to infect either the lower or upper airways. Generally, a lower respiratory tract infection is harder to transmit but is more severe, while an upper respiratory tract infection spreads more easily but is less severe.
The other unique feature of SARS-CoV-2 is its ability to infect both lower and upper airways, which could probably be due to its harnessing of the furin enzyme. It is believed that this ‘double-edged sword’ of the virus could explain why it can spread between asymptomatic people – a phenomenon that has created a huge challenge in its control.
Question: is it possible that the virus still transmits while stuck to the upper airways, before digging deeper to cause severe symptoms? This cannot be confirmed at the moment. Nevertheless, it is hypothetically plausible because the virus is new, and most of its biology and pathological manifestations are still a mystery.
Ever since COVID-19 was declared a pandemic, SARS-CoV-2 hasn’t significantly changed in its transmission pattern. It’s mutating like all viruses, but none of the mutations has dominated all the others – suggesting that none of all the mutations so far is predominant and especially important. With the number of transmissions that have been recorded thus far, SARS-CoV-2 has been remarkably stable.
There’s one possible exception though. A few of the SARS-CoV-2 viruses that have been extracted from some Singaporean COVID-19 patients lack some genes that were also absent from the 2003 SARS-CoV during later stages of the epidemic. These missing genes were believed to render the original virus less potent, but it’s still early days yet to state emphatically that the same will apply to SARS-CoV-2. Indeed, why some coronaviruses are mild and others deadly is still unclear.
Scientists can however offer a preliminary account of the disease process of COVID-19 after infection with SARS-CoV-2. Once infected, the virus likely attacks the ACE-2-positive cells that line the airways. Dying cells slough away, filling the airways with debris and carrying the virus deeper into the tissues, and finally into the lungs. As the infection progresses, the lungs are clogged with dead cells and fluid – causing breathing difficulties.
Like all other immune systems, the human immune system protects the host by attacking all invading pathogens, including coronaviruses, leading to inflammation and temperature spells (fever). In extreme cases, however, the immune system can cause more damage than the virus itself.
For example, blood vessels could open up and allow T-cells to travel to the site of infection and cause destruction; however, if the blood vessels open the floodgates and become exceptionally fluid, the lungs will be overfilled and become overwhelmed with fluid – causing damage to the pulmonary cells.
These damaging actions are generally caused by an avalanche of cytokine storms, and have been attributed to the several deaths during the H5N1 bird flu outbreaks, 1918 flu pandemic, as well as the 2003 SARS-CoV outbreak. Could they also be the cause of some of the severe cases of COVID-19? When there is an avalanche of cytokine secretion, the immune system goes ‘wayward’ and attacks indiscriminately without hitting the specific target.
When this happens, the immune system can attack the host organs themselves; people also become more susceptible to other infectious agents. This could explain why some COVID-19 patients end up with serious complications such as secondary infections, cardiac problems, and auto-immune diseases.
But why are some COVID-19 patients overwhelmed with the disease while others experience only mild or no symptoms? Current data available indicate that age is a factor. The elderly are more susceptible because their weakened immune systems cannot mount an effective defence, while children are less susceptible because their immune systems, though maybe not effective in defence, are nevertheless less likely to elicit a cytokine storm.
Several other factors like the unpredictability of their immune systems, the amount of virus exposed to, the population of other microbes in their bodies, and the person’s genes can also play a role. In general, it is still a mystery and scientists are trying to decipher why within the same age group some COVID-19 patients are asymptomatic or either have mild or severe disease outcomes.
Coronaviruses, like the flu virus, are deemed seasonal (winter) viruses. It is believed that the thin layers of liquid that line our lungs and airways get even thinner in cold and dry air, making it a huge challenge to effectively evict the invading viruses.
Unfortunately, that might not matter for the COVID-19 pandemic. At the moment, the virus is rampaging throughout the entire world; and this is likely to douse any effect of seasonal variations. Classic examples are Italy (in the temperate zone), U.S.A. (in the temperate zone), Singapore (in the tropics), Algeria (Saharan desert interior), and Australia (which is still in summer).
Indeed, a recent modelling study reported that SARS-CoV-2 can be active and spread any time of year – debunking the conspiracy theories saying that the weather is going to have any effect on the spread. Health authorities are also recommending that unless people can be disciplined enough to stick to social distancing and the other preventive protocols, the Summer alone can’t stop spread of COVID-19.
All in all, the scary part is the apparent lack of surveillance networks for coronaviruses as exists for flu. We don’t even have information on how the viruses mutate year on year. Currently, the research has been slow, leading to a paucity of reliable research data on this novel coronavirus.
How is COVID-19 treated?
There are currently no FDA-approved specific treatments for COVID-19 infections. When a patient tests positive for SARS-CoV-2 infection, doctors treat the symptoms as they arise. In a sense, because the virus causes respiratory disease, it is those associated symptoms that are treated.
Currently, clinical management of COVID-19 patients includes supportive care such as supplementary oxygen and ventilatory support (in critical cases), and infection prevention. Also, we don’t use antibiotics because they won’t work against viruses.
Any therapy in view?
Some clinical trials are currently underway to find a vaccine against the MERS coronavirus. This could be good news, because if successful a solid groundwork for a SARS-CoV-2 vaccine and COVID-19 treatment can be laid
Other drugs, like hydroxychloroquine and azithromycin combination therapy, that have been approved for other ailments are being studied in clinical trials across the world. Both drugs, particularly Hydroxychloroquine, have in-vitro potency against SARS-CoV-2. Currently, Chloroquine or Hydroxychloroquine are recommended by the Centre for Disease Control (CDC) in the U.S. for treatment of COVID-19 patients in several countries.
A group of researchers have also recommended the use of a drug called baricitinib (for treating arthritis) against the new coronavirus The use of this drug was based on the idea that SARS-CoV-2 can infect the lungs by interacting with specific receptors on the surface of lung cells, and that baricitinib may be able to disrupt the interaction between the virus and receptors.
This mode of disruption also plays out in a lot of other virus-cell interactions, but whether it will be effective as a full-fledged drug against COVID-19 remains to be seen. The good news is that baricitinib has already gained official approval as a treatment for other conditions – meaning that it is largely safe. Consequently, it may bypass the extensive, rigorous, and long processes which pre-clinical trials require of any new drug.
>>>The writer is a Professor in Virology, Molecular Medicine and Nanotechnology at Regent University College of Science and Technology, Accra.
