A scientist works in a bio-safety level 2 laboratory at KU Leuven's The Rega Institute for Medical Research in Leuven, Belgium. The institute is currently trying to find a treatment for Covid-19. — Reuters
Covid-19 is the name of the disease arising from the infection of a new (novel) coronavirus designated as SARS-CoV-2, also known as 2019-nCoV or the Wuhan virus.
It is the latest in a line of zoonotic diseases (or zoonoses) that has plagued humans ever since evolution begun. Zoonoses are diseases that are transmissible from a different species to humans.
Covid-19 is now certain to become a pandemic likely to affect not only people, but also the economic well-being of the planet.
The origins of the SARS-CoV-2 virus infecting humans is widely believed to be a wet market in Wuhan, China, which sold wildlife; although the exact original animal carrier is still unknown.
This is all not news by now to most people, so the second part of this article will focus on some other facts behind the reality that many humans will now be living under the shadow of Covid-19 until a cure or vaccine can be found.
There are generally three strategies to counter a new viral disease.
The first strategy is to apply broad-spectrum anti-virals such as interferon agonists.
The second strategy is to use the genome of SARS-CoV-2 and screen for existing drugs that can target susceptible parts of the genome to disable or destroy it.
For example, virus structures targeted could be PLpro (papain-like protease), 3CLpro (3-chymotrypsin-like protease), RdRp (RNA-dependence RNA polymerase) and helicase, among others.
The third strategy is to devise entirely new compounds that target specific points in the genome to either cripple the virus or kill it entirely.
The first strategy using broad-spectrum anti-virals has generally proved ineffective due to the complexity of the SARS-CoV-2 genome.
The third strategy normally requires at least several years of development and testing, although it would probably be the most successful strategy if such compounds can be devised quickly.
That leaves the second strategy.
Several existing drugs that may be able to counter SARS-CoV-2 have already been identified.
These include PLpro inhibitors (e.g. ritonavir), 3CLpro inhibitors (e.g. lopinavir/ritonavir) and RdRp inhibitors (e.g. ribavarin).
In the future, it is highly probable that treatments involving a cocktail of drugs may be the most effective method to treat Covid-19, depending on factors such as the infection stage, co-existing medical conditions, age and others.
Although high hopes are being placed on drugs like remdesivir, chloroquine and oseltamivir, there is currently no established cure for Covid-19.
In any case, any cure would be highly dependent on access to the drugs, which is influenced by production capacities, financial costs and geographical availability.
Note that any cure would also be highly lucrative for the inventors, and therefore, there may be a degree of self-promotion involved.
There is also research into using antigens from people who have recovered from the virus.
As for vaccines, they may be available one day, but it will probably take years before one is developed, tested and marketed.
Several cases of people who have fully recovered from Covid-19, but subsequently became re-infected, are causes for concern.
It may indicate that the disease is bi-phasic, which means that the disease may recur after a seeming first recovery.
The current outbreak is still young and it would be very worrying if more bi-phasic cases are detected.
The SARS-CoV-2 virus has a huge 29,903 bases in its RNA (ribonucleic acid) genome, which means that like all other complex coronaviruses, it is prone to mutation.
And it seems that variations of the original virus already exist.
A new strain of SARS-CoV-2 affecting Italy (and now, other European countries) has been very recently isolated at Luigi Sacco hospital in Milan; this strain differs genetically in several areas from the original coronavirus in Wuhan.
Future mutations are to be expected and it remains to be seen if such new mutations have different health implications compared to the Wuhan virus.
Such variations may also affect efforts in finding a cure.
The most curious statistic about Covid-19 is the mortality rate, which rose from 2.15% on Feb 14 (2020) to 3.45% on Feb 29 (2020), according to data from the US Centres for Disease Control and Prevention (CDC).
On the surface, there may be several simplistic (and incorrect) explanations for this.
One is that Covid-19 kills people who have the disease longer.
Another is that medical services may be unable to cope with the rising number of infected persons, and therefore, more untreated people are dying.
Yet another inaccurate assumption may be that the diseased demographic is shifting to older people who have a higher death rate.
Although plausible, there is also a statistical flaw in all of the above assumptions: they do not include the time between detection of disease and death, which we shall call T.
The value of T needs to be established to know the true case fatality rate (CFR).
If we assume a low value of 7 (days) for T, then the number of deaths reported on Feb 29 (2020) needs to be reflective of the total infected pool seven days earlier on Feb 22 (2020).
This gives a CFR of 3.76%, which is the number of deaths on Feb 29 (2,923) divided by the number of infected cases on Feb 22 (77,673).
If T is 15 instead, then the CFR would be 4.54%, which is the number of deaths on Feb 29 (2,923) divided by the number of infected cases on Feb 14 (64,437), 15 days earlier.
The value of T would vary hugely by region, depending on factors such as demographics, availability of medical resources, quality of detection, etc.
As such, determining plausible values for T in different regions remains an important exercise that has not been fully done.
Compounding the problem is that the numbers of infected people are significantly under-reported, perhaps by up to 400% (or even more in some countries).
An infected sick person seeking treatment will almost certainly get included in the statistics (including a subsequent death); however, symptomless, but infected, people may never get counted.
Imperial College London in the United Kingdom estimates that each infected person is likely to infect at least 2.5 other people before detection if not quarantined.
There are many confirmed cases of infected people who do not display any symptoms, at least for significant periods of time, while being extremely infectious to other people.
Due to the contagious nature of SARS-CoV-2, it is feasible that the disease cannot now be contained, especially if it takes hold in countries that cannot impose quarantines on entire cities.
For example, it would be practically impossible for the United States and the European Union to lock down whole cities.
China has done this and may have prevented Covid-19 from becoming an even worse national epidemic.
Regarding demographics, one observable characteristic of Covid-19 is that it is more lethal for older people and people with other diseases.
The statistics indicate that infected people aged between 10 to 39 years have a 0.2% chance of dying from Covid-19.
This risk rises to 0.4% for those aged between 40-49 years, 1.3% for those between 50-59 years, 3.6% for those between 60-69 years, 8% for those between 70-79 years and 14.8% for anyone older than 80 years.
The good news is anyone nine years old or younger has no additional mortality risk from Covid-19.
For infected people with cardiovascular disease, the risk of dying from Covid-19 is 10.5%, with diabetics having an enhanced death risk of 7.3%.
People with chronic respiratory diseases have a risk of 6.3%, high-blood pressure sufferers are 6% more likely to succumb, and patients with cancers have a 5.6% death risk from Covid-19.
In light of the above, prevention is infinitely better than a non-existent dependable cure, especially if one is older or has pre-existing medical conditions.One ironic twist is that SARS-CoV-2 in humans originated from (unnecessary) human desire for wild animal meat – and the anagram of “coronavirus” is “carnivorous”.
Chris Chan works in advanced statistical and mathematical modelling of risks in large investment banks and often applies his analytical expertise to other fields such as chemistry and biochemistry. He also writes the Curious Cook column for StarLifestyle. For more information, email starhealth@thestar.com.my. The information provided is for educational purposes only and should not be considered as medical advice. The Star does not give any warranty on accuracy, completeness, functionality, usefulness or other assurances as to the content appearing in this column. The Star disclaims all responsibility for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such information.
