Perspectives on SARS-CoV-2
Image credit: John Nicholls, Leo Poon and Malik Peiris, LKS Faculty of Medicine, and Electron Microscopy Unit, The University of Hong Kong
The coronavirus pandemic is, in essence, a multi-disciplinary problem: disrupting economies, exemplifying political conflicts, and revealing issues with social structures worldwide. However, its root most definitely lies within the sphere of science. Moreover, we’ve all seen the disastrous impact of misinformation worldwide – the anti-vaxxers, the anti-mask activists. In light of this, Asklepian will publish articles weekly, as an introduction to the mystical world of rigorous, evidence-based medicine. Feel free to leave any ideas, suggestions or advice in the comments section, and we look forward to diving into the magnificent mystique of scientific medicine with you!
Our initial posts will be based on COVID-19, as there is much to learn from this pesky little virus. Our first article (this article) will be about the basics – a brief stint into how SARS-CoV-2 (read as SARS-Coronavirus-Two) infects humans, the virus which causes the disease COVID-19. We’ll then build on this foundation to explore the plethora of scientific literature published in the past year, ranging from the disruption that SARS-2-CoV causes in the heart and the brain to the molecular stratagems that underlie the basis of vaccine construction. Lastly, we’ll conclude with a dive into the clinical methods of Evidence-based medicine, to understand how a fringe concept suggested by Professor David Sackett in 1981 has transformed into HKU Med’s core philosophy, and how this has contributed to Homo Sapiens’ response towards the pandemic.
As a starting point, let’s first explore the path that COVID takes through our body. Looking at the body of a coronavirus, we see its genome wrapped in protective plates, with antennae sticking out. Similar to all living creatures we know of, viruses carry their genetic information in nucleic acids; and a coronavirus’s single-stranded RNA is packed tightly under its layers of membrane, capsid and nuclear proteins. This RNA is considered as “positive sense”, as its sequences of nucleotides are directly translated into viral proteins. In an infection, the coronavirus floats into our breathing system and lands on the surface epithelium cells along the mucosal surfaces in our respiratory tract. The next process is reminiscent of Brownian motion – the antennae will now search for a particular enzyme (called ACE2) on the cell’s surface, and then attach to the enzyme tightly. As is in most biological systems, this process is random, with successful infection dependent on the coincidental meeting of the virus and ACE2. This mechanism exploits the internal mechanism of the cell – it would automatically envelop the virus and give the viral genome a highway into the innards of the cell where it can reproduce. An important point is how the affinity (stickiness) of the antennae (the Spike protein) to the receptor is rather high; and we’ll revisit this as we explore how therapies for COVID-19 are being developed.
Why is SARS-2-CoV so infectious? To understand this, we must take a look at the capabilities of our body in regulating water. We discovered the mechanisms of the Renin-Angiotensin-Aldosterone System (RAAS) in the early 1900s, which helps maintain an adequate volume of water in our body. In a case of water shortage, our kidney secretes the hormone renin, which activates another hormone – Angiotensin 1. However, Angiotensin 1 needs to be converted into Angiotensin 2 in order to exert its effects of water retention: like constricting blood vessels (to raise bp) and inducing thirst. The conversion of angiotensin from 1 to 2 has to be controlled precisely, and coincidentally, the enzyme responsible for inhibiting this conversion is exactly the one that SARS-CoV-2 exploits to get into our cells – angiotensin-converting enzyme 2 (ACE2). These ACE2 enzymes are mostly expressed in the lungs, ripe for SARS-CoV-2’s exploitation, although tissues like the Heart, Kidneys, Gut and Eyes also express them. Then, should therapies for COVID-19 be based around suppressing ACE2 receptors in order to reduce openings for SARS-CoV-2 to use? Sadly, studies show that common blood pressure lowering drugs that increase levels of ACE2 worsened the condition of some patients, which might be due to its essential functions in the RAAS (South, Tomlinson,
Edmonston, Hiremath, & Sparks, 2020, p. 305). With scientists debating on this contentious topic, we may be able to get more effective therapies as we understand more (Vaduganathan et al., 2020, p. 1654).
Moving on, let’s look at the COVID-19 pandemic from a birds’ eye perspective. Statistically, SARS-CoV-2 is quite an infectious virus, with a Basic Reproductive Number (R0, pronounced R nought) of 2.2-2.5 with a range of 1.8-2.6. In other words, each infected patient will on average infect 2.2 to 2.5 more people. Compared to other viruses like SARS-CoV (2.0-3.0), influenza (1.5) and the incredibly infectious measles (12-18), SARS-CoV-2 is relatively infectious in the coronavirus family. The goal of public health policy is to push down the R number to less than 1, such that the number of patients will decrease, and that is exactly what mitigation strategies like compulsory facemasks and reduced gathering are doing. Thereby, with different public health strategies, different Effective Reproductive Numbers (RE) can be calculated for different countries. By tracing the infection paths of patients, we can calculate the R number as an objective metric of how effective the public health strategies are. This is also one of the most important metrics for constructing mathematical models on transmission dynamics.
Besides the biological nature of the coronavirus, human factors can also affect SARS-CoV-2’s infectivity. Air quality can have a significant impact on the transmissibility of respiratory viruses. With many respiratory bacteria hitching a ride on the millimetre-scale particles suspended in the air, thus spreading between geographical regions by diffusion of the aerosolized particles at a much quicker pace than would be expected from simple diffusion. This phenomenon can be seen in Europe and Northern China, where the smog is trapped near the surface of the ground by the cold, heavy air (Coccia, 2020). Much of the bacterial community’s structure is shaped by the type or concentration of air pollutants (Gao et al., 2017), which could be a big factor in the opportunistic infections accompanying COVID-19. The research on how viruses interact with airborne microparticles is promising but still in its infancy. Further research may explain why the levels of PM2.5 were correlated with the mortality rates in COVID-19’s tremendous wave in Italy (Groulx et al., 2018).
Throughout this article, we’ve looked at how SARS-CoV-2 infects humans, is related to age-old renal physiology concepts, can be described mathematically by reproductive numbers, and may even be affected by the inconspicuous levels of air pollution. Hopefully, this can show you how modern evidence-based medicine is very much multidisciplinary!
Bibliography
Coccia, M. (2020). Factors determining the diffusion of COVID-19 and suggested strategy to prevent future accelerated viral infectivity similar to COVID. Science of The Total Environment, 729, 138474. https://doi.org/10.1016/j.scitotenv.2020.138474
Gao, J.-F., Fan, X.-Y., Li, H.-Y., & Pan, K.-L. (2017). Airborne Bacterial Communities of PM2.5 in Beijing-Tianjin-Hebei Megalopolis, China as Revealed by Illumina MiSeq Sequencing: A Case Study. Aerosol and Air Quality Research, 17(3), 788–798. https://doi.org/10.4209/aaqr.2016.02.0087
Groulx, N., Urch, B., Duchaine, C., Mubareka, S., & Scott, J. A. (2018). The Pollution Particulate Concentrator (PoPCon): A platform to investigate the effects of particulate air pollutants on viral infectivity. Science of The Total Environment, 628–629, 1101–1107. https://doi.org/10.1016/j.scitotenv.2018.02.118
South, A. M., Tomlinson, L., Edmonston, D., Hiremath, S., & Sparks, M. A. (2020). Controversies of renin–angiotensin system inhibition during the COVID-19 pandemic. Nature Reviews Nephrology, 16(6), 305–307. https://doi.org/10.1038/s41581-020-0279-4
Vaduganathan, M., Vardeny, O., Michel, T., McMurray, J. J. V., Pfeffer, M. A., & Solomon, S. D. (2020). Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19. New England Journal of Medicine, 382(17), 1653–1659. https://doi.org/10.1056/nejmsr2005760