The known unknowns of COVID-19

What makes the COVID-19 epidemic so frightening for people and businesses is how much we don’t know…

While the culprit has been identified and given a name (the virus SARS-CoV-2), medical researchers are still at the early stages of understanding the disease. In the UK, we are already seeing the impact of that uncertainty as store shelves are emptied and the stock market crashes.

The key concerns that currently face the UK are:

We don’t have a good understanding yet of how widespread the infection is

Testing for the virus initially focused on people displaying severe symptoms, their immediate contacts, and recent arrivals from outbreak areas. However, nearly 95% of active cases display mild symptoms and may not get tested. As the infection has spread, some countries have widened the number of people tested, but others have only just begun to carry out widespread testing, and there is no consistent approach between countries. Without the data on who is or isn’t infected, it is difficult to predict how severe an outbreak will eventually become and where new outbreaks could occur.

The tests which are presently available can only detect the virus in a person who is currently infected, as it is based on amplifying small quantities of the viral genome to levels that can be measured. A test for antibodies against the virus would allow us to find out who has been exposed to the virus, long after the person has recovered. This would give a better picture of the true level of infection. Unfortunately, tests for antibodies are still in development and have only been used experimentally. However, before testing for antibodies can be widespread, health authorities need to be convinced that they display accurate results. The risk is that if they are not sufficiently accurate (for example, indicating that someone has had the disease when in fact they haven’t), it could make things worse than no test at all.

Infection may not bring immunity

When we are infected, our immune system recognises the proteins on the outside of the virus as something novel and unwanted, leading to the production of antibodies that bind onto and “kill” the virus. If we encounter the virus a second time, our bodies quickly recognise the virus and it’s neutralised, giving us immunity to re-infection. Viruses can escape this immunity if they acquire mutations that change the shape of their outer proteins – the change in shape means that the immune system will not recognise the new viral strain and therefore will not be able to mount a quick response. Influenza is an example of one such virus with a high mutation rate that can return as a new seasonal strain year-after-year.

The genome of COVID-19  is a single strand of ribonucleic acid (RNA), unlike our own genomes which are double strands of deoxyribonucleic acids (DNA). When DNA is replicated, our cells are able to check the new copy against the original and fix any mistakes that may occur.  RNA is not usually copied from other RNA strands except by viruses, and viruses like SARS-CoV-2 can’t proofread the copies. This lack of proofreading gives COVID-19 a high mutation rate, and that could allow new seasonal strains to evolve. Not all RNA viruses are seasonal however – for some viruses any change in the shape of the outer proteins is likely to neutralise it, new strains do not emerge, and immunity is effectively life-long. Measles, another single stranded RNA virus, is one such example.

Of the six other coronaviruses that infect people, two (SARS and MERS) appear to confer life-long immunity, although as these are recent diseases, this is not known for certain. Immunity to the other four species fades after a year, and these viruses reappear regularly to cause mild colds. The adaptability of SARS-CoV-2 has implications both for the long-term impact of the virus on human health and the ability to develop an effective vaccine, and at this point we do not know how long immunity could last.

We don’t know when an effective treatment will become available

Currently the only treatment for Covid-19 is supportive, with ventilators required for the most critical cases. Several drugs are being tested against the disease, with ones that block replication in other RNA viruses (e.g., influenza and Ebola) showing some promise. An effective vaccine is not expected for 12 to 18 months, long after the worst of the epidemic has passed.

Human behaviour will make the infection difficult to control, and we don’t know how people will react to a prolonged shutdown

The virus SARS-CoV-2 is truly novel and not one against which humans have any background immunity. In theory, the infections could increase until enough people have had the disease that it becomes difficult for it to find new hosts, at which point the infection will fade away (believed to be between 60% to 80% of the population). Current estimates are that the average number of new infections generated by each infected person are around 2.5, but these estimates are biased by a lack of reliable information on the number of milder infections, so the true number could be significantly higher. Reducing this rate of infection is crucial to managing the epidemic and although lockdowns are proving effective in China the risk is that once a lockdown is relaxed, the virus could re-emerge and start new outbreaks.

The wildcard is going to be human behaviour – even in these first days of “social distancing” in the UK we are seeing people ignoring the warnings and congregating in large numbers. Once rates of infection start to drop, people will want to relax the lockdown and businesses will push to reopen, potentially causing the epidemic to flare up again.

Despite these uncertainties, from an epidemiological point of view, the longer “social distancing” continues, the greater the chance of controlling the epidemic and the fewer people who become infected, potentially seriously.

Unfortunately, the longer these restrictions exist, the greater the potential damage to the economy.  Airlines, the tourism industry, restaurants and theatres are either operating a skeleton service or are shut completely, with those many businesses that depend on foot traffic now following. If “social distancing” cannot be maintained and the epidemic cannot be controlled, the epidemic could be prolonged to the point that it impacts transportation, trade, and those industries like agriculture that depend on the movement of workers.

Only time will tell what long term impact COVID-19 will have on the UK economy in general. What is certain is that we are in unprecedented times, and COVID-19 will bring changes that will affect the UK for years to come.

Do you have any questions? Please contact Keith at keith.church@4-most.co.uk