Covid-19: A guide to epidemiology

 By Raman Gnanalingham

Abstract

In this article, I will outline the key features of epidemiology, which is the study of epidemics. This will be in relation to the current Covid-19 outbreak, caused by the SARS-CoV-2 virus. I will also discuss the susceptibility of certain population demographics and the reasons as to why the virus has spread so quickly. Finally, I will cover the key approaches to managing the outbreak of the disease, through the lens of an epidemiologist.

Introduction

On December 31^st, 2019, China alerted WHO to several cases of unusual pneumonia in Wuhan, a port city of 11 million people in the central Hubei province. The virus at the time was unknown. One week later, France had also confirmed its first case, with the number of those infected rapidly increasing ever since.
The first death in China was recorded on January 9th. Over the space of almost 4 months, we have gone from this to 230,000 deaths across the world and with 185 out of 195 countries having people infected with the virus. Most affected countries have enforced restrictions in movement, public gatherings and closed schools and universities. The question that must be asked is how we got to this state of social and economic chaos, despite the fact that Covid-19 has a death rate of around 1%, compared to the estimated 90% death rate of Ebola. This can largely be explained through epidemiology, the study of epidemics.

Defining epidemics and classifying diseases

An epidemic can be defined as an outbreak of a disease that spreads rapidly and affects multiple individuals at the same time [3]. The term epidemic is often used broadly to describe any problem that has grown out of control. What is important to note when classifying epidemics is that during one, the disease is actively spreading and is widespread.
A pandemic is a type of epidemic that refers to how far the disease has spread across the earth, generally describing one that affects large sections of the world. Declaring a pandemic allows national and global public health agencies to respond to the disease at a national or even global level. Despite the fact that it is at times difficult to distinguish between an epidemic and pandemic, in the case of the coronavirus, the disease has spread to such a large extent and with such speed that it has quickly become a major pandemic.
In contrast, a disease becomes endemic once it has a constant presence in one specific location. Malaria, for example, has been a constant presence within parts of Africa. To take this one step further, an outbreak is even more general, simply referring to the sudden onset of spread of disease in one region, such as dengue fever last year in Hawaii.
Ultimately, epidemiologists use these terms of classification to better understand a disease and be able to respond faster with a policy that better manages the spread of disease.

Figure 1:
A history of Pandemics, comparing the number of deaths [5]. Figures as reported on April 30^th, 2020.

Comparing Pandemics

The death rate of Covid-19 has greatly increased in recent weeks. Considering that in early March only 6000 people had been killed by the virus., by late April approximately 230,000 had sadly died. However, compared to the 50 million killed by the Spanish flu in the early 1900s, and approximately 40 million killed by HIV/AIDS, the death rate of the coronavirus still remains relatively low (Figure 1).
What is important to appreciate is the recent improvement in management of pandemics, which is what has kept diseases from causing so much damage; the techniques of case isolation, movement restrictions and social distancing are relatively recent. We have constantly been learning from managing previous pandemics and this is what has led to our current policies being much more effective.
Coronaviruses in general refer to a family of viruses which often cause respiratory diseases; all of us at some point have had a coronavirus infection, namely the common cold. Covid-19, the specific disease responsible for the current pandemic, is caused by the SARS-CoV-2 virus, in much the same way AIDS is caused by HIV virus [6].
The last coronavirus pandemic was the one caused by SARS-CoV in 2002 in China, although this was better controlled with only 774 deaths worldwide. Perhaps the closest comparison to the situation we currently face is the 1918 H1N1 influenza pandemic, known as the Spanish flu, as it was a destructive and very transmissible respiratory virus that lasted over a long period of time with no available vaccine, similar to Covid-19. Given that the Spanish Flu killed 45 million, it is clear why we are so concerned about the current coronavirus pandemic.

Most affected demographics

SARS-Cov-2 virus enters the body via the mucous membranes of the eyes, nose and mouth, either by air droplets released during a cough or sneeze from an infected individual or by a contaminated hand touching those areas. The incubation period for the virus ranges from 1-14 days, most commonly around five days.
A paper published by the Imperial College London’s Covid-19 Response team in mid-March has used mathematical modelling to map the likeliest percentage of cases across different age groups, the critical care bed capacity needs and death rate. Crucially, those over 70 are far more in danger of being hospitalised with more severe symptoms (43-71%) than those who are younger. Infective diseases in general will typically affect extremities of age, given that these are the people who typically have the weakest immune system [7].
However, epidemiologists are unsure as to why Covid-19 more likely targets the elderly. Source?One suggestion may be because some of the receptors involved with the virus are also associated with cardiovascular disease. Therefore, Covid-19 may be exacerbating cardiovascular disease, which actually tends to be more present in older adults. This is because as you get older, heart and blood vessels stiffen, with an increased chance of fatty deposits along the vessels as well, which worsens the cardiovascular system. These factors perhaps make the symptoms worse in adults. An alternative hypothesis as to why the elderly are more affected is that the elderly have more probably been previously exposed to a version of the coronavirus. This immunologically primes them to have a more severe reaction to Covid-19 Source?.

Figure 2: Line graph outlining the relationship between age groups, risk of hospitalisation, needing critical care treatment and infection fatality ratio [7].

Why does it spread so fast?

Another question that scientists have had when trying to understand the SARS-CoV-2 virus is why it is spreading so quickly. Coronaviruses, like SARS-CoV-2, have infected people before, most notably the SARS-CoV virus in the SARS epidemic in China (2003). This virus shares 86% of its DNA with SARS-CoV, and yet only killed approximately 800 people, which raises the question of what makes this novel coronavirus so much more infectious [9].
Previously, it was suggested that SARS-CoV-2 possessed a spike protein which recognises and is activated by furin enzymes in the human body. Furin is found in lots of human tissues, including the lungs, liver, and small intestines, which means that the virus has the potential to attack multiple organs, allowing it to spread much quicker. Furin inhibitors therefore have been suggested as a potential treatment, however given the damage they cause to cells in general in stopping many cell processes, a targeted approach would be required to avoid toxicity [9].
In addition, the spike protein binds to the angiotensin-converting enzyme (ACE2) receptor on human cells. SARS-CoV-2 binds 10 times more tightly to host cells than the SARS-CoV virus. This higher affinity to human cells is perhaps what is contributing to its faster spread [9]. The ACE2 enzyme causes vasoconstriction and is involved in regulating blood pressure. There is ongoing research as to whether certain blood pressure medications that affect ACE2 receptors, could put people at risk of getting the virus.

Key considerations in epidemiology

The primary job of epidemiologists is to understand how diseases spread, and crucially what methods can be used to reduce the health and economic impacts of disease epidemics. Currently, two key policies are considered in tackling Covid-19:

1. Mitigation: This is a focus on slowing (but not stopping) the spread of disease. The term “flattening the curve” has been mentioned frequently by politicians, and this relates to spreading out the cases over a longer but more manageable time period, thus preventing the healthcare system becoming overwhelmed. This helps to reduce the peak healthcare demand and protect those most at risk.
2. Suppression: Each person with Covid-19 infects around 2 to 3 people (making the R₀ number lie between 2 and 3). Suppression is a policy to reverse growth of the epidemic to the point where the R₀ number is below 1. Think of this as a “delaying the curve” as opposed to flattening.

The two policies initially seem quite similar yet have subtle differences regarding the extent of disease management. Both however use tracing of contacts and Non-Pharmaceutical Interventions (NPIs). These are measures which do not involve drugs or vaccines that can reduce transmission by limiting contact and are used as tactics to try and combat the spread of the disease. Table 1 outlines a list of NPIs that could be considered [7]; the values in the table are obtained from mathematical simulations of likely outcome and using data taken from censuses.

Policy	Description
Case isolation at home	Symptomatic cases stay at home for 7 days, thus reducing non-household contacts by 75%.
Voluntary home quarantine	After the identification of a case displaying symptoms is found in a household, all household members remain at home for 14 days. Contact with the community reduces by 75%
Social distancing of those over 70 years old	Reduce workplace contact by 50%, increase household contact by 25%, and reduce other contacts by 75%
Social distancing of whole population	All households reduce outside contacts by 75%, with unchanged school contact, and 25% reduced by 25%
Closure of universities and schools	Closure of all schools and 75% of universities, increasing household contact rate by 50%

Table 1: List of NPIs considered in epidemic management from the Imperial College study [7].

Impact of NPIs

Epidemiologists at Imperial used mathematical modelling to predict how the number of patients requiring critical care treatment in hospitals will vary [7]. This is based on applying different combinations of the NPIs discussed in Table 1.
Looking at figure 4, we can see what will happen should no action be taken against the virus (ie the red line). This allows the epidemic to peak early and likely overwhelm the healthcare system, notably the number of critical care beds available. This is likely to result in a sudden spike in deaths, which consequently would cause significant social and economic damage.
In suppression (orange line), the general aim is to keep cases to a minimum for as long a time period as required. This is done by a combination for NPIs and other physical measures, such as border control and contact tracing. By preventing contact between people, the R₀ number is pushed below one and thus spread is ‘suppressed’. However, the population is unable to gain herd immunity to the disease [10]. Herd immunity refers to the concept of multiple people in the community who are immune to a disease (either through previous infection or by vaccine) preventing a disease from spreading to an uninfected person, acting as a barrier to the virus. Consequently, a delayed second peak occurs at a later point, when the NPIs are relaxed. However, by delaying the outbreak of the epidemic, we gain time for healthcare systems to prepare and for scientists to create a vaccine/ drugs which are effective against the virus, with the hopes of removing the second peak altogether.
In mitigation (green line), NPIs are used to flatten the curve, so the average daily number of cases is spread out over a more manageable time period. This also provides time for the health care system to react to the epidemic and enables some degree of herd immunity to develop.
Suppression appears to have worked well in some countries such as China, South Korea, and New Zealand. This however was only achieved by the fast action to implement strict isolation and zonal lockdown of affected cities. In Britain, suppression was not successfully achieved, and so a policy of mitigation is currently being pursued with some success. Moreover, in the UK, the number of critical care beds is being increased to manage the peak outbreak of severely unwell patients.

Figure 3: Line graph to illustrate the impact of mitigation (green line) and suppression (orange line) strategies in the number of patients with severe illness needing treatment in a hospital critical care bed. The red line indicates the severe outbreak of illness if no interventions are undertaken. The dotted blue line indicates the number of critical care beds available.

Conclusion

To conclude, the principles suppression and mitigation are key strategies to consider when managing the spread of a disease. Covid-19 is arguably the most serious pandemic which has occurred in modern times and is yet to be brought under control. Understanding the mechanism of spread and age groups targeted by the disease are crucial to managing the crisis. Ultimately, we rely on past experiences and decisions when dealing with pandemics to decide how to react to these situations, and so Covid-19 will be a vital learning point to use when dealing with future pandemics.

References

1. “Pneumonia Of Unknown Cause.– China” 2020. [online] Available at: https://www.who.int/csr/don/05-january-2020-pneumonia-of-unkown-cause-china/en/ [Accessed 25 April 2020].
2. “Coronavirus: Which Countries Have Confirmed Cases?” 2020. [online] Available at: <https://www.aljazeera.com/news/2020/01/countries-confirmed-cases-coronavirus-200125070959786.html> [Accessed 25 April 2020].
3. Merriam-webster.com. 2020. \’Pandemic\’ Vs \’Epidemic\’. [online] Available at: <https://www.merriam-webster.com/words-at-play/epidemic-vs-pandemic-difference> [Accessed 25 April 2020].
4. intermountainhealthcare.org. 2020. What’s The Difference Between A Pandemic, An Epidemic, Endemic, And An Outbreak?. [online] Available at: <https://intermountainhealthcare.org/blogs/topics/live-well/2020/04/whats-the-difference-between-a-pandemic-an-epidemic-endemic-and-an-outbreak/> [Accessed 27 April 2020]
5. LePan, N., 2020. Visualizing The History Of Pandemics. [online] Visual Capitalist. Available at: <https://www.visualcapitalist.com/history-of-pandemics-deadliest/> [Accessed 27 April 2020].
6. CleanLink. 2020. SARS-Cov-2 And COVID-19: What\’s The Difference?. [online] Available at: <https://www.cleanlink.com/news/article/SARS-CoV-2-and-COVID-19-Whats-The-Difference–25264> [Accessed 27 April 2020].
7. Neil M Ferguson, Daniel Laydon, Gemma Nedjati-Gilani, et al, Imperial.ac.uk. 2020. Report 9: Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand [online] Available at: <https://www.imperial.ac.uk/media/imperial-college/medicine/sph/ide/gida-fellowships/Imperial-College-COVID19-NPI-modelling-16-03-2020.pdf> [Accessed 27 April 2020].
8. The Conversation. 2020. Why Are Older People More At Risk Of Coronavirus?. [online] Available at: <https://theconversation.com/why-are-older-people-more-at-risk-of-coronavirus-133770> [Accessed 27 April 2020].
9. Medicalnewstoday.com. 2020. Why Does SARS-Cov-2 Spread So Easily?. [online] Available at: <https://www.medicalnewstoday.com/articles/why-does-sars-cov-2-spread-so-easily#Key-receptor-on-human-cells> [Accessed 27 April 2020].
10. Alex James, Shaun C Hendy, Michael J Plank, et al, Suppression and Mitigation Strategies for Control of COVID-19 in New Zealand [online] Available at < https://www.medrxiv.org/content/10.1101/2020.03.26.20044677v1> [Accessed 30 April 2020]

About the Author

Raman Gnanalingham is a 16 year old student from Greater Manchester, England. He is currently studying Maths, Further Maths, Biology and Chemistry and hopes to study Medicine at University. Raman enjoys music in his spare time, playing the piano and clarinet to a high standard.