Coronavirus: Cutting Through the Confusion

This post was written by Ed Roberts.

Over the last year we’ve all become amateur epidemiologists with newspapers feeding us a constant stream of news about the course of the pandemic, the promise and subsequent delivery of numerous vaccines, and the hopes for a release from lockdown. Amongst these numerous articles are a lot of scientific terms which are often unclear to a non-expert audience, and these are seldom explained (herd immunity anyone?). Adding to this confusion is that what we know about COVID-19 is rapidly changing and developing as we continue to study this new disease and start seeing the results from vaccines in the real world. To help with reading future articles in the field, here is a handy guide to some of the terms used and controversies covered in the news.

So what is COVID-19? COVID-19 is the disease caused by the virus SARS-CoV-2; while this may seem confusing this is similar to how AIDS is the disease caused by the HIV virus. However, in coverage of COVID-19 you may see references to “the virus that causes COVID-19” or to SARS-CoV-2, both of these refer to the same thing.

But I’ve heard about coronavirus, is SARS-CoV-2 just a name for coronavirus? While SARS-CoV-2 or the COVID-19 virus both refer to the same thing Coronavirus is not the same thing, although it is often used that way. There are a whole family of Coronaviruses which all share similar genetic and overall structure. These were identified as human pathogens in the 1960s. There are several human coronaviruses, many of which cause common colds or other relatively mild lung infections. There have been other coronaviruses which have caused more severe outbreaks in recent history. Notably, this includes SARS-CoV which caused the SARS outbreak in 2002 and MERS-CoV which caused an outbreak of MERS in 2012.

Ok, but where did this new virus come from? The origin of SARS-CoV-2 has been investigated extensively with the World Health Organisation (WHO) visiting Wuhan recently to look into various possibilities. The likeliest source of the virus causing COVID19 is that the virus jumped from bats to humans. This has been discussed widely and has been a source of conspiracy theories and racist rhetoric. But this kind of thing isn’t unique to our recent history, many other viruses jump from animals into humans and these are called zoonoses. Indeed, as humans invade the habitats of more and more species and keep various species of animals in close contact, this kind of event becomes more common. Bird flu, Ebola, HIV, Nipa and Zika are all zoonotic diseases. There are more than 1,400 species of bats around the world and these harbour at least 1,300 coronaviruses: MERS, SARS and SARS-CoV-2 – all examples of zoonoses from this family of viruses. Understanding the origin of zoonoses can inform future monitoring strategies but in recent times it has been discouraged to name viruses based on where they were reported as it is uninformative and encourages stigma.

Great, but now that it’s here we need to get the R-number down, but what does that mean? The R number represents how many people an infected person is likely to infect. It is a handy concept in epidemiology to characterise the transmissibility of a disease, for example measles is highly contagious and has an R number of 12-18 while influenza has an R number of 0.9-2.1. SARS-CoV-2 has an R number somewhere between 3.3 and 5.7 and so, in the absence of interventions, each infected person would infect roughly another 4 people meaning it would rapidly spread throughout a population. With interventions like social distancing, vaccinations, and mask wearing we can reduce the actual observed R number to below 1 and the number of infected people will gradually decrease. This is why seemingly small changes around 1 are very significant, with numbers greater than 1 leading to growth in the population, and numbers less than 1 leading to reduced infection rates.

Will this all be solved though when we have all been infected and achieve Herd Immunity? Herd immunity is a situation where a high enough proportion of the population are immune to an infection, which ensures protection for the population as a whole. Remember that the R-number refers to how many an infected individual is likely to spread the disease to in a population. The more people who are immune, the fewer contacts an infected individual makes with people who could be infected. By reducing this number you ensure that, as a whole, people infect less than 1 other person. In this sense, you may get some infections, but you can’t get an outbreak. The level of protection needed for herd immunity depends on a few things including how infectious the virus is and how effective anti-viral immunity is. So although the level of immunity in the population will reduce the R number, it’s unlikely that we will totally eliminate SARS-CoV-2 through herd immunity, just as we haven’t eliminated the common cold.

Now that we have the vaccine this will help us bring down the R number, but how do the vaccines work; are they changing our DNA? The first vaccine which reported its effectiveness as protecting against SARS-CoV-2 was produced by Pfizer and is an RNA vaccine. RNA stands for ribonucleic acid – an acid that can be found in all living cells. The vaccine also produced by Moderna is similarly an RNA vaccine. These are a new vaccine technology and work by injecting RNA into a patient which sounds like science fiction or genetic engineering. In reality, RNA serves as a blueprint for a protein; in this case the RNA vaccines contain the blueprints for the SARS-CoV-2 spike protein. Once inside the patient, this RNA is picked up and read by immune cells which then make the spike protein before using that to train an immune response to recognise that protein in future. This means that when exposed to the virus in future the immune system is already primed and ready to go – leading to the infection either not establishing at all, or being cleared more rapidly. The RNA itself is not particularly stable and is cleared, it also doesn’t interact with the DNA inside host cells so there is no worry about any genetic changes occurring.

So what are the other vaccines that are available?  Other major vaccines, AstraZeneca/Oxford, Janssen, and Sputnik V are all more conventional. For these vaccines a different virus has been modified so that it expresses the spike protein. This new virus doesn’t cause disease but does stimulate an immune response. The follow up from this is very similar to the RNA vaccine where if in future you encounter the actual SARS-CoV-2 virus, your immune system is primed to eliminate it before it can make you sick.

But what about second doses? Most of the vaccines have been trialled where people are given 2 doses of the vaccine with a short period of time between those 2 doses. The idea is that you challenge the immune system and get an initial response, and thereafter you rechallenge them with the vaccine again to get an even more robust response in future. This led to some concerns being raised after the UK government decided to prioritise getting as many people their first dose and left the second doses for longer than were tested in the clinical trials. As vaccinations moved forward, the efficacy of the first dose has now been established and it looks like even that first dose provides quite a lot of protection. But you still do need that second dose at some point!

What exactly is vaccine efficacy though? Is there an obvious “best” vaccine? Many newspaper articles have been written about the efficacy of different vaccines but it can be unclear what these mean and so it is important to read carefully! The most common efficacy number refers to the reduction in moderate to severe disease and hospitalisations. This means that numerous people received either the vaccine or a placebo (dummy substance) and then were monitored. The number of people in each group who became moderately or severely ill were compared. In this way you can use the placebo group to determine roughly the percentage of people expected to become ill, and can see what reduction there is in the vaccinated group.

However, it is possible to also measure reductions in mild disease, transmissions, and deaths. These are all being calculated now that larger populations are being vaccinated and all of these give different and complementary information. For example, reduced transmission will lower the R number while reductions in deaths will not; as such it is important to check what the statistics being presented actually refer to.

The vaccines target the spike protein, but what does that mean? The spike protein is a protein which sticks out from the surface of the virus and is made of 2 subunits. One of these subunits recognizes and binds to the protein ACE2 which is found on cells in the lungs. This binds the virus to the cell, and then another protein on the cell surface activates the spike protein and then the other subunit drives cell invasion. This allows the virus to get inside the host cell where it can take over the cellular machinery to produce more virus particles. As such, this spike protein is important for function but also covers the surface of the virus meaning it’s the main thing exposed to the immune system while outside of infected cells. Antibodies against this spike protein can block the virus associating with the cell surface thereby preventing it from continuing to infect.

So how do we have variants with changes in the spike protein if it’s that important? When a virus reproduces within a host cell there is a low chance that a mutation will be introduced. These mutations are likely to make the resulting virus less effective because they will disrupt normal function. However, rare mutations might make the virus more able to spread or to evade our immune defences. These rare events lead to new variants which can spread more effectively. Since the spike protein plays such an important role in infection many of these variants have changes in their spike proteins. The spike proteins are also the target of the vaccines which currently exist against SARS-CoV-2 and so these changes may allow variants to escape from the protection current vaccines provide. This is why new studies of vaccine efficiency are looking at their ability to protect from new variants and why vaccine studies carried out before the emergence of these variants are hard to compare to the studies being carried out now. 

If we don’t eliminate the virus, what does that mean for the future? Recently, discussion has moved from the idea of elimination to the idea that COVID-19 may become an endemic disease in the population. This means that the disease may be regularly found in the population at a fairly stable level from year to year. That would mean that COVID-19 became a disease we will have to live with in the long term. There is speculation as to what this might mean, however, observations from previous diseases suggests that over time the disease might become less severe.

So what does it all mean? Well before COVID-19 there were estimates of how much disruption to the world an influenza pandemic with a higher death rate than we have seen with COVID19 would cause. The estimates were much lower than we have seen with this pandemic, suggesting consequences were grossly underestimated. Moving forward we can take the lessons from this pandemic, be they personal lessons about how small behaviours like hand washing can prevent the spread of disease; public health lessons about the importance of surveillance or even lessons about how we interact with the natural world and the risks that brings for human health, all of which will hopefully make us better equipped for future challenges. While the COVID-19 pandemic has been a once in a lifetime experience we must remember that it’s not an aberration  but, rather reflects some of the challenges associated with a global community living closely with animals and encroaching on new environments.