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It takes at least two things to cause a viral infection in the body: a virus and a receptor in the body that this virus can attach to. In the case of COVID-19, the receptor is angiotensin-converting enzyme 2 (ACE2) receptor and the virus is SARS-CoV-2.

The link between ACE2 receptors and SARS-CoV-2 was probably one of the first things that scientists discovered while studying the 2019 novel coronavirus infection. Almost every research paper has some mention of these receptors and how they help the COVID-19 infection gain entry into the body.

Normally, of course, ACE2 receptors help to maintain crucial bodily functions like our blood pressure. Read on to know the connection between ACE2 receptors and SARS-CoV-2, and why COVID-19 causes shortness of breath and other respiratory symptoms.

Read more: COVID-19 timeline

  1. What are ACE2 receptors?
  2. ACE2 and COVID-19: why SARS-CoV-2 produces respiratory symptoms
  3. Doctors for Why coronavirus SARS-CoV-2 affects the lungs

The ACE2 receptors are actually a part of a hormonal system in our body that is responsible for controlling blood pressure and fluid and electrolyte balance. The system is called RAS - renin-angiotensin system.

This system has three hormones - renin, angiotensin and aldosterone - which act as enzymes in three different reactions in your body. 

A hormone is a chemical compound that is directly released into the bloodstream by specialised glands called endocrine glands. Hormones relay messages from one part of the body to another and help regulate various processes in the body. An example of a hormone is insulin, which is released by the pancreas and promotes the uptake of sugars by the liver.

Enzymes, on the other hand, are compounds that catalyze (speed up) all the biological reactions in the body. Pepsin is an enzyme that is released into the stomach; it helps break down proteins in food.

The RAS system includes organs such as the lungs, kidneys, liver, brain and the circulatory system.

The function of the RAS system: In response to low blood pressure, specialised cells in our kidneys release the hormone renin into the bloodstream. This renin breaks down a protein called angiotensinogen (which is released by the liver and is constantly present in the blood) into angiotensin 1.

Now, angiotensin 1 is an inactive protein that needs to be converted into angiotensin 2 to be active. This conversion is done by the angiotensin-converting enzyme (ACE). This enzyme is present in ample amounts in the blood vessels of our lungs and kidneys.

ACE then binds to the ACE receptors present on the surface of the blood vessels of lungs and kidneys and constricts the blood vessels. This leads to an increase in blood pressure - or balance thereof if you already had low blood pressure. Angiotensin 2 also leads to the release of a hormone called aldosterone from the kidneys, which improves kidney function and the sodium-potassium (electrolyte) balance in the body. 

This is why most patients with high blood pressure and chronic kidney disease are given ACE receptor blockers or ACE inhibitors. 

Cell surface receptors are specialized molecules (usually proteins) that are present on the surface or through the surface (like a tunnel) of all body cells. These receptors help something from the outside (an enzyme or hormone, for example) to gain entry into the cell and perform its function.

Angiotensin-converting enzyme 2

ACE2 is very similar in structure to ACE. However, it does the opposite of what ACE does. That is, it brings down blood pressure.

ACE2 converts the active angiotensin 2 into angiotensin (1-7), which dilates blood vessels. ACE2 helps reduce the risk of fibrosis in the body (scarring or hardening of body tissues) and reduces the risk of heart disease.

Receptors for ACE2 are found in the lungs, liver, oral and nasal mucosa, stomach, intestines, kidney and brain.

Viruses are basically a complex of proteins, carbohydrates, lipids and genetic material (DNA or RNA). They are unable to replicate on their own and are considered to be non-living when outside a host - more accurately, they are on the cusp of a living and non-living thing.

Simply put, viruses are parasites that need a host to live and grow. And to get into the host’s body, these parasites use various mechanisms - most of which include specialising themselves to trick the host cells and gain entry into the host. Once the virus enters a cell, it takes over the cellular machinery and starts replicating itself, producing more copies of itself that release the first cell and infects all the surrounding cells. 

In the case of COVID-19, the causative virus SARS-CoV-2 binds to the ACE2 receptors. 

Since the ACE2 receptors are present in the lungs, this virus causes respiratory disease and spreads through droplet infection. So if you touch a contaminated surface, the virus sticks to your palms, and when you touch your face, specifically your mouth, eyes, ears or nose, it can easily gain entry into your respiratory tract. 

We do know that that the ears and nose are connected through the eustachian tube - a tube present in the middle ear that goes to the back of the nose and helps maintain pressure in the ear. 

Though the exact link between eyes and respiratory system is not clear, experts say that tear ducts may have some link with the nose and hence lungs.

ACE2 receptors are also found in the intestines and hence it is considered to be a possible entry route for the COVID-19 virus.

Read more: Tips for caring for someone with COVID-19 at home

Dr. Neha Gupta

Dr. Neha Gupta

संक्रामक रोग

Dr. Lalit Shishara

Dr. Lalit Shishara

संक्रामक रोग

Dr. Alok Mishra

Dr. Alok Mishra

संक्रामक रोग

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References

  1. Lu Roujian, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet. 2020 Jan-Feb; 395(10224): 565-574.
  2. Fountain JH, Lappin SL. Physiology, Renin Angiotensin System. [Updated 2019 May 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan
  3. Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. Functions of Cell Surface Receptors.
  4. Chamsi-Pasha Mohammed A.R., Shao Zhili, Tang W. H. Wilson. Angiotensin-Converting Enzyme 2 as a Therapeutic Target for Heart Failure. Curr Heart Fail Rep. 2014 Mar; 11(1): 58–63. PMID: 24293035.
  5. Patel Vaibhav B., Zhong Jiu-Chang, Grant Maria B., Oudit Gavin Y. Role of the ACE2/Angiotensin 1–7 Axis of the Renin–Angiotensin System in Heart Failure. Circulation research; 118(8). 1313-1326.
  6. Microbiology Society [Internet]. UK; Are viruses alive?
  7. Bitko Vira, Musiyenko Alla, Barik Sailen. Viral Infection of the Lungs through the Eye. J Virol. 2007 Jan; 81(2): 783–790. PMID: 17050596.
  8. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631–637. PMID: 15141377.
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