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ACADEMIA Letters COVID-19: We Are at War, by Analogy, with the Coronavirus Olen R. Brown, Dalton Cardiovascular Research Center, the University of Missouri Sir Winston Churchill once said: “Apt analogies are among the most formidable weapons of the rhetorician”[1]. Ordinary folk also often use analogies to explain complex matters. An analogy to war is appropriate for COVID-19. On my desk is a bit of concrete taken from a wall. It was given to me by a Russian postdoctoral student who visited Berlin when the wall came down in 1989. That wall brings to mind a famous analogy in the ‘Iron Curtain Speech’ of Winston Churchill: “From Stettin in the Baltic to Trieste in the Adriatic, an iron curtain has descended across the continent.” You can listen to those words here [2]. There was, of course, no actual curtain, iron or otherwise. But, the analogy was powerful. It became a defining image. It described a geopolitical reality and then a physical reality, the Berlin Wall. Analogies can help us to better understand COVID-19 and the starkly frightening medical and scientific news that is the daily essence of the pandemic. Facts about this intrusive virus overwhelm us. Not since WWII have people been so affected by events almost entirely outside their control. Now, however, instead of daily or weekly news, everyone is exposed to complex data and analyses that change hourly. New terms, much speculation, and unattractive alternatives challenge us. We could ignore these if the consequences weren’t so personally disruptive. What we don’t know can be both misleading and frightening. A quote from Nobel Laureate Marie Curie, the discoverer of the radioactive element Radium, is appropriate. “Nothing in life is to be feared, it is only to be understood. Now is the time to understand more, so that we may fear less” [3]. A size analogy is useful for the Coronavirus war with the people of Earth. Imagine a fantastic machine that magnifies a coronavirus to the size of a basketball. Imagine that you are magnified identically. You are now the size of the planet Mercury! How can something Academia Letters, August 2021 ©2021 by the author — Open Access — Distributed under CC BY 4.0 Corresponding Author: Olen R. Brown, dr.olen.brown@gmail.com Citation: Brown, O.R. (2021). COVID-19: We Are at War, by Analogy, with the Coronavirus. Academia Letters, Article 2921. https://doi.org/10.20935/AL2921. 1 as small as this virus harm a human? The answer is clear when we understand two things: the enormity of the number of viruses in each person ill with COVID-19 and a virtual war is raging. This war is not on the scale of armies and countries. It is a war waged at the microscopic level. It is not waged with airplanes, tanks, and guns. It is fought with unfamiliar and deadly molecular weapons. The human body has approximately 30 trillion cells [4] ฀about the same in magnitude as the U.S. national debt. The coronavirusmust find its way into a human cell to multiply. It is the ultimate parasite; too poor in the molecules of life to bear children on its own. At war, it must make up for its size by sheer numbers and it must ‘borrow’ the machinery of life from the human cells it invades. The war begins when the virus attempts to invade and infect a human [5]. Social distancing mandates that people stay six feet apart. The virus can spread by airborne particles and aerosols [5]. Relative to its tiny size, to find its way into a human nose, the virus must travel a great distance. Comparatively, for a person, this distance is 22,000 miles ฀slightly more than three times the distance from Honolulu to Moscow. The virus has no form of transportation (no rocket ship). An analogy is useful to understand the viruses’ problem. Usain Bolt, the world’s fastest human (who was diagnosed with COVID-19; thankfully, without symptoms) can run the 100-meter dash at 27 miles per hour. Converting this to a ‘Bolt Time Scale Analogy’, it is fair is to measure the distance traveled for Bolt and by the virus in units of their body sizes. Bolt is six feet five inches tall and can run approximately six times his body length per second. It would take 19.5 million viruses to equal Bolt’s height. If the coronavirus had legs and could run as fast as Bolt, using the Bolt Time Scale, it would take the tiny virus approximately 40 days (a Biblical time unit) to cross the six feet of mandated social distancing. This is impractical. So, the virus hitches a ride on the spaceship called a respiratory droplet. It can cross the six feet of social distancing in about seven seconds in a quiet room; it takes only 40 milliseconds when propelled by an explosive cough. By further analogy, infection by the COVID-19 virus begins with a battle. The virus must gain entrance into a castle, the human cell. That cell has an impenetrable wall but it has a weakness as does the fortress castle. The cell’s weakness is the ACE-2 receptor which by analogy is the castle drawbridge. The virus can only enter here and only by appearing to be a desired visitor (by analogy, the Trojan horse). The virus is as poor as a church mouse but as sly as a court jester. It has only the blueprint for making the virus. It subverts the cell’s factories and makes hundreds of viruses in a few hours. These viruses slip out through the castle wall and each can sneak into another cell. The battle continues. The virus population increases like compound (not simple) interest applied to the principle which is growing explosively. One virus enters a cell and 200 leave in a few Academia Letters, August 2021 ©2021 by the author — Open Access — Distributed under CC BY 4.0 Corresponding Author: Olen R. Brown, dr.olen.brown@gmail.com Citation: Brown, O.R. (2021). COVID-19: We Are at War, by Analogy, with the Coronavirus. Academia Letters, Article 2921. https://doi.org/10.20935/AL2921. 2 hours. The 200 become 40,000; then 8,000,000… The seriousness of the COVID-19 illness is, by analogy, similar to the outcome of a war. The virus battles not with poison or deliberate destruction. It fights by taking over the factories inside the human cell. It impairs their normal functions. The race begins for the human cell to enlist the immune system to provide the specific weapon to attack the virus. Meanwhile, the collateral damage wreaks havoc that ravages tissues and entire organs. An individual cell can win a battle but the war can be lost. Or, the damage may be tolerable and destruction of the virus complete and peace returns to the body. Vaccines can also be understood as mimicking the Trojan horse because they enter human cells by subterfuge. Once inside, the mRNA (messenger ribonucleic acid) of the vaccine stimulates the immune system to produce antibodies. Antibodies are analogous to counterspies that seek out and destroy invading covid viruses. Vaccines for COVID-19 were produced in an unbelievably short time, through heroic scientific effort and the political will to expedited approval. Three vaccines were approved by the FDA for use in the U.S. by February 27, 2021 [6]. The first was the mRNA, Pfizer-BioNTech vaccine. The Moderna vaccine also is an mRNA vaccine [6] and it is very similar to the Pfizer vaccine. It can be stored in a refrigerator for at least 30 days. Both vaccines are approximately 95% effective and they use similar, relatively new technology. A small bit of genetic code (positive-stranded mRNA of the SARS CoV-2 virus) gives human cells instructions (blueprints) for making the ‘spike’ protein of the virus. This spike protein is analogous to the key that opens a door to let the virus into the human cell. The mRNA of the vaccine gives instructions only for making the spike protein. No new viruses are made and thus no infection occurs. The tiny spike protein stimulates the immune response and antibodies are produced. These antibodies attach to the spike of an invading COVID-19 virus particle and prevent it from entering the human cell. The Johnson and Johnson vaccine was produced by a significantly different method [6]. A harmless (to humans) adenovirus was engineered to provide a shell to incase a small bit of COVID-19 genetic code information. This code provides instructions only for spike protein, not a complete, infectious virus. This stimulates the production of antibodies. It requires only one shot; it is 85% protective and it can be stored refrigerated for about three months [7]. A rare, severe type of blood clot was associated with vaccination after about 6.8 million doses had been administered. The CDC and FDA jointly recommended a pause (not a stop-use order) “out of an abundance of caution”. The recommendation was lifted on April 23 after a thorough investigation [6] [8]. Along with vaccinations a new term, herd immunity, entered common usage. Herd immunity occurs when a high percentage of individuals become immune. It can occur by vacAcademia Letters, August 2021 ©2021 by the author — Open Access — Distributed under CC BY 4.0 Corresponding Author: Olen R. Brown, dr.olen.brown@gmail.com Citation: Brown, O.R. (2021). COVID-19: We Are at War, by Analogy, with the Coronavirus. Academia Letters, Article 2921. https://doi.org/10.20935/AL2921. 3 cination or disease recovery. It is sometimes explained using theoretical constructs (R and R0) that mathematically describe the infectiousness of a disease [9]. By analogy, infections spread like links in a chain. Infectiousness is increased by branching of the chain and stopped by breaks in links. On average, one person may infect one with no branches; many when there is a branching chain; or none with a broken chain. Immunity breaks the chain. One COVID-19 case, on average, infects two or three people [10] and ฀50% of a population must be immune for herd immunity to be truly effective [11]. Many cases are asymptomatic [12] and recovered cases have immunity. Community quarantines, the use of masks and physical distancing, and other unknown variables, influence virus spreading. Vaccinations theoretically could end the pandemic when the chain branching is reduced below one [9]. The COVID-19 war is not over, it is not yet won, but I end this story as I began with words of Churchill [13]. He said, just after the first decisive victory by the Allies in WWII at El Alamein, “Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning.” References 1. Churchill: A Study in Oratory [Internet]. Int. Churchill Soc. 2016. https://winstonchurchill. org/publications/finest-hour/finest-hour-069/churchill-a-study-in-oratory/ 2. Listen to Churchill’s Iron Curtain Speech [Internet]. History. https://www.history.com/ speeches/churchills-iron-curtain-speech 3. Top 25 Quotes by Marie Curie (of 52) [Internet]. -Z Quotes. https://www.azquotes.com/ author/3506-Marie_Curie 4. How Many Cells Are in the Human Body? Types, Production, Loss, More [Internet]. Healthline. 2018. https://www.healthline.com/health/number-of-cells-in-body 5. Poydenot F, Abdourahamane I, Caplain E, Der S, Haiech J, Jallon A, et al. Risk assessment for long and short range airborne transmission of SARS-CoV-2, indoors and outdoors, using carbon dioxide measurements. :41. 6. Comparing the COVID-19 Vaccines: How Are They Different? [Internet]. Yale Med. https://www.yalemedicine.org/news/covid-19-vaccine-comparison 7. Johnson & Johnson one-shot coronavirus vaccine authorized in the U.S. for people 18 Academia Letters, August 2021 ©2021 by the author — Open Access — Distributed under CC BY 4.0 Corresponding Author: Olen R. Brown, dr.olen.brown@gmail.com Citation: Brown, O.R. (2021). COVID-19: We Are at War, by Analogy, with the Coronavirus. Academia Letters, Article 2921. https://doi.org/10.20935/AL2921. 4 and over [Internet]. https://www.cbsnews.com/news/covid-vaccine-johnson-and-johnsonauthorized-emergency-use/ 8. COVID-19 Vaccines. FDA [Internet]. FDA; 2021. https://www.fda.gov/emergencypreparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-vaccines 9. Delamater PL, Street EJ, Leslie TF, Yang YT, Jacobsen KH. Complexity of the Basic Reproduction Number (R0) - Volume 25, Number 1—January 2019 - Emerging Infectious Diseases journal - CDC. Available from: https://wwwnc.cdc.gov/eid/article/25/1/ 17-1901_article 10. Herd Immunity [Internet]. WebMD. https://www.webmd.com/lung/what-is-herd-immunity 11. What is herd immunity for the coronavirus? [Internet]. WebMD. https://www.webmd. com/lung/qa/what-is-herd-immunity-for-the-coronavirus 12. Brown OR. Asymptomatic COVID-19; We Don’t Know What We Don’t Know. Preprints; 2020.https://www.preprints.org/manuscript/202007.0681/v1 13. Churchill: “This is not the end” (Nov. 1942) [Internet]. 2010. https://www.youtube.com/ watch?v=pdRH5wzCQQw Academia Letters, August 2021 ©2021 by the author — Open Access — Distributed under CC BY 4.0 Corresponding Author: Olen R. Brown, dr.olen.brown@gmail.com Citation: Brown, O.R. (2021). COVID-19: We Are at War, by Analogy, with the Coronavirus. Academia Letters, Article 2921. https://doi.org/10.20935/AL2921. 5