COVID-19: A Clinician’s Perspective Simplified. (Part 1)
This is a two-part article discussing the disease COVID-19 from a clinician’s standpoint. Part one of this article explores the structure of the virion, its transmission, and infectivity, along with some explanations of the pathogenesis of the disease. Part two discusses the diagnostic facilities and the treatment modalities available for COVID-19.
What is the Novel Coronavirus?
The virus, which is called SARS-COV-2, belongs to a family of Betacorona viruses, a family that also contains the SARS-COV-1 and the MERS viruses. Members of this family are positive-sense, single-stranded, RNA viruses that are enveloped.
The 2 main points to consider about the structure of the virus is that it has a single-stranded RNA molecule inside its core (which is the genetic material of the virus) and the spike proteins (which the virus employs to attach to ACE 2 receptors). Although many other viral structures are currently being identified and even possibly used to make novel treatment modalities, but for the simplified purpose of this article I will skip over them.
The virus is thought to be of zoonotic origin, as is common for most coronaviruses. Since the viral genome is approx. 96.2% similar to the BatCoV RaTG13, a coronavirus found in bats (Zheng, 2020), it is presumed that the virus is of bat origin.
How do I get infected?
There are 3 main proposed transmission routes for SARS-COV-2:
- Feco-Oral route
Aerosol transmission is simple. If an infected person coughs or sneezes, he expels viral particles inside tiny water droplets around him, and if a non-infected person inhales those “aerosol” then he can catch the disease. Simple. A recent study has shown that an infective dose of viral particles may remain airborne for up to 3 hours and that simply talking, or breathing even, may generate an infective load of aerosols. (van Doremalen N, 2020)
Fomite transmission is a bit tricky and very hard to be mindful of. If an infected individual contaminates a surface, for example by touching it (assuming his hands are contaminated with the virus already) or coughing on it, and a non-infected person touches the surface afterwards and then continues to touch his face then he may contract the disease. Although no tangible timeline of the viability of the SARS COV 2 virion on surfaces has been established, there has been research done on the viability of SARS COV 1 and the MERS virus, indicating that the life of the virus on a fomite surface may be as long as a few hours to even several days (G. Kampf, 2020).
Like fomite transmission, the fecal-oral route of transmission is also very tricky to control. Infected individuals shed the virus in their feces (Hindson, 2020) and not only contaminate bathroom surfaces, if proper hygiene is not observed, but can also massively spread the disease in areas where proper sewage disposal is unavailable.
How infective is the virus?
A measure of the infectivity of the virus is the basic reproductive number. The basic reproductive number, or R0 (pronounced R-naught), of SARS COV 2 is between 2 to 3 (Heng Li, 2020). This means that a single infected person can infect up to 3 more people. Those 3 can go on to infect a total of 9, those 9 can go on to infect a total of 27, and so on. This is called an exponential increase and is one of the reasons why this virus is so difficult to control. The virus is simply too infective.
Measures to avoid infection:
Although research is inconclusive about the effectiveness of masks and other protective equipment against the community spread of SARS COV 2, it is still a good idea to observe as much caution as possible.
- Wear masks
- Practice social distancing
- Wash hands thoroughly
- Avoid touching your eyes, face, and nose
- Take a bath after coming home from work\outside
- Go out as little as possible
- Disinfect all groceries\other purchase items using surgical alcohol or soap
- Seek medical attention if you feel sick
The pathophysiology of COVID-19 (simplified):
To get a concise grasp of all the effects of the infection on the body, it is prudent to start from the beginning.
Research has quite conclusively proved that the virus attaches to ACE 2 receptors found on many human cells. The virion enters the body via the respiratory system where it usually targets the type 2 pneumocytes found in the alveolar epithelium. These pneumocytes are responsible for the production of surfactant, a soapy material required to reduce the surface tension of the fluid film on the alveolar wall. Without surfactant, the surface tension becomes too great and the alveolar wall collapses upon itself. As alveoli collapse and are unable to accommodate inspired air, the functional volume of the lung decreases.
In addition, cells infected with the virus release a host of chemical mediators, some of which are called inflammatory cytokines. These cytokines include molecules like Interleukin-1, Interleukin-6, Tumor Necrosis Factor–α, IFN-α/β, IFN-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), etc. These mediators contribute to a host of responses, including macrophage and neutrophil transport into the alveoli (which in turn release more inflammatory mediators), and increasing the permeability of capillary membranes causing fluid influx into the lung interstitium. This fluid hinders the exchange of gases between the alveolar air and the pulmonary circulation, and the condition is termed as viral pneumonia.
Both the collapse of the alveoli and the consolidation of the lung tissue (fluid filling into the lung) contribute to the compromised lung function. This is observed clinically as a decrease in SpO2 (percentage fraction of oxygen-saturated hemoglobin relative to total hemoglobin) and an increase in pCO2 (partial pressure of carbon dioxide in the blood). When the body cannot get sufficient Carbon Dioxide out and sufficient Oxygen into the blood, one of its responses is to increase the breathing rate. This is seen clinically as the breathlessness,or dyspnea, seen with patients of COVID-19. The body also tries to expel the inflammatory fluid building up into the alveolar spaces by coughing. Some of the inflammatory mediators also leak into the systemic circulation, are transported to the hypothalamus and cause it to raise the resting body temperature. Prostaglandin – E is particularly implicated in this, and the resulting fever is seen in almost 80% of patients with COVID-19 (Kenneth McIntosh, 2020).
The disease is not only limited to the respiratory system. As more and more data is becoming available, it is becoming exceedingly clear that COVID-19 is a systemic disease. One of the other systems predominantly involved is the cardiovascular system. COVID-19 has documented acute cardiovascular sequelae (like myocarditis and thromboembolism) and proposed chronic sequelae (like dyslipidemia, hypertension, increased risk of stroke\MI, etc.) (Zheng J. , 2020). The mechanisms of disease in this system is unclear, but it is suspected that the virus gains entry via the ACE 2 receptors, like the respiratory tissue, and damages cells of the cardiovascular system. Since ACE 2 receptors are upregulated in patients of preexisting cardiovascular disease, this may explain the severity of clinical symptoms observed when such patients get superimposed COVID-19 (Zheng Y. M., 2020).
Another observation made early in the pandemic was that some patients, particularly the elderly presented with added symptoms of gastrointestinal distress (Jinyang Gu, 2020). It is proposed that the SARS COV 2 virion, through binding of ACE 2 receptors, enters gastrointestinal tissues and results in symptoms like diarrhea. Indeed, in my clinical practice as an ICU doctor, I have seen one elderly patient of COVID-19 who presented to us with the chief complaint of fever and diarrhea (so much so that she went into hypovolemic shock) without any symptoms of cough.
The derangement of liver function and renal function can also be contributed to the propensity of the SARS COV 2 virion to infect cells having the ACE 2 receptor, but exact mechanisms are unclear. One of the proposed theories is that these derangements usually occur in severe cases and it can be argued that they are the result of a systemic inflammatory reaction (Saraladevi Naicker, 2020). If the viral load is large enough, which is usually the case with severe infections, so extensive is the inflammatory mediator release (called a cytokine storm) that a body-wide inflammatory response results. Vasodilation occurs throughout the circulation, along with loss of circulating blood volume as edema develops, and blood pressure falls causing organ damage. This is called a septic shock.
Other manifestations of COVID-19 include neurological complications like headache, dizziness, myalgia, anosmia, encephalitis, encephalopathy, and stroke (FJ, 2020) (Mao L, 2020), as well as dermatologic manifestations like maculopapular rashes, necrotic skin lesions and COVID toes (Mazzotta F., 2020).
This is the end of part 1 of this article. The next post will discuss the diagnostic and treatment modalities available for COVID-19. Thank you.
Coronavirus. (2020, May 01). Retrieved from worldometer: https://www.worldometers.info/coronavirus/
FJ, C.-A. (2020, May 1). Neurological complications of coronavirus and COVID-19. Rev Neurol., 311-312. doi:10.33588/rn.7009.2020179
G. Kampf, D. T. (2020, 02 16). Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents. The Journal of Hospital Infection, 104(3), 246-351. doi:10.1016/j.jhin.2020.01.022
Heng Li, S.-M. L.-H.-L.-K. (2020, March 29). Coronavirus disease 2019 (COVID-19): current status and future perspectives. Int J Antimicrob Agents. doi:10.1016/j.ijantimicag.2020.105951
Hindson, J. (2020). COVID-19: faecal–oral transmission? Nature Reviews Gastroenterology & Hepatology, 259.
Jinyang Gu, B. H. (2020, May). COVID-19: Gastrointestinal Manifestations and Potential Fecal–Oral Transmission. Gastroenterology, 158(6), 1518–1519. doi:10.1053/j.gastro.2020.02.054
Kenneth McIntosh, M. (2020, May 08). Coronavirus disease 2019 (COVID-19): Epidemiology, virology, clinical features, diagnosis, and prevention. Retrieved from UpToDate: https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-epidemiology-virology-clinical-features-diagnosis-and-prevention
Mao L, J. H. (2020, April 10). Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. doi:10.1001/jamaneurol.2020.1127
Mazzotta F., T. T. (2020). A NEW VASCULITIS AT THE TIME OF COVID-19. Bari, Italy: Dermatologia Pediatrica.
Saraladevi Naicker, C.-W. Y.-J.-C.-H. (2020, May). The Novel Coronavirus 2019 epidemic and kidneys. Kidney International, 97(5), 824–828. doi:10.1016/j.kint.2020.03.001
van Doremalen N, B. T. (2020). Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. New England Journal of Medicine, 1564–1567. doi:10.1056/NEJMc2004973
Zheng, J. (2020). SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat. International Journal of Biological Sciences, 1678–1685.
Zheng, Y. M. (2020, May 05). COVID-19 and the cardiovascular system. Nature Reviews Cardiology. doi:10.1038/s41569-020-0360-5