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COVID-19 Update May 15, 2020: Where the Virus Lands on our Cells – The ACE-2 Receptor, an Update

By Dr. Arthur Lavin

Glossary

  • Virus– a type of germ that consists solely of a bit of genetic material (DNA or RNA) wrapped in a protein coat.  The coat gets the genes into the target cell where the genes force the cell to make zillions of new viruses, and on it goes.
  • Coronavirus– a species name of a number of different viruses.  Called corona because its protein coat is studded with spike shapes that form a crown, halo, or corona of spikes
  • SARS-CoV-2– the specific name of the new coronavirus
  • COVID-19-the name of the illness that the new coronavirus is causing
  • Endemic– an illness always present in a region.  One could say strep throat is endemic in the US
  • Epidemic– a sudden burst of an illness that comes and goes over a limited time
  • Pandemic– an epidemic that bursts across the world not just one region
  • Spreadability– how contagious is the disease, how many people will end up infected
  • Severity– what harm does the disease cause, in terms of  how sick you get and how many it will kill
  • Mask- a mask is a loose-fitting cloth or textile that covers the mouth and nose loosely.  A surgical mask is a mask used in surgery
  • Respirator-  for the purposes of the COVID-19 pandemic and other respiratory illnesses, a respirator is a mask that fits very snugly or tightly to the user’s face.  An N95 mask is a respirator.
  • Personal Protective Equipment (PPE)- PPE are any item that covers any part of the body with the design and intent of keeping viruses in the environment from infecting the wearer of the PPE. PPE’s include all masks (which includes respirators), face shields, eye shields, gloves, gowns.
  • Ventilator- a ventilator is a machine that can force a person unable to breathe to inhale and exhale and control both effectively.  They are sometimes called respirators, but during this pandemic the word respirator is now reserved for reference to a tightly fit mask.
  • Live Virus Swab– this is the swab which attempts to swipe live virus from one’s nose or throat to see if you are currently infected.
  • Antibody Test- (aka serology test) this is the blood test which looks for antibody to the SARS-CoV-2 virus to see if you have been infected in the past.

 

Spreadability

One brief note here.  I encourage people to look at the data on how this virus, the SARS-CoV-2 virus, spreads on their own.  So here is a list of some key websites that give us a real look at how various nations, and regions in the US are managing this threat to us all:

NY Times  An excellent overview of data site.  You can even enter Cleveland to see how are trends are, up to today.

Financial Times  This resource offers clear graphics that break down trends in cases and deaths by nation, region, even some cities

Worldometer    The Worldometer site is a comprehensive list of every nation, its trends, and also each state.

Topos   Topos is unique.  Using a very large number of perspectives it presents trends across the US that cover a huge range of questions.  Which counties have the fastest rate of rise?  How do rates of COVID vary by demography, income, etc.  A treasure.

https://covidtracking.com/data  Want to know how any state is doing, this is the best site for this information.

www.endcoronavirus.com   This site was compiled by an MIT professor of complex systems, it takes very complex trends and presents a simple graphic for many nations, on a key question- how is each nation stopping the spread of this virus?

Severity- A look at the ACE-2 Receptor and How Severity Follows this Protein

Real Answers has presented information about the protein that is the target of the SARS-CoV-2 virus before, but new advances in our understanding may help us all understand why we are hearing about so many more parts of the body being hurt by COVID-19.

What does a protein on the surface of our cell have to do with COVID-19?

Remember that viruses are tiny packages of genetic codes wrapped in a protein coat?   All viruses do is find a way to enter a cell, have its genetic code make zillions of copies of viruses that then do the same to many other of our cells.

So a virus has a fundamental problem- how to get inside that next cell?  If it can’t gain entry, its genetic codes remain dormant, it needs to get to our cells internal machinery for its genetic codes activate to force our cells  to make new viruses.

But our cells are built to keep enemies out, most viruses never gain entry.

For a virus to succeed, it needs to pick a lock, find a protein on the surface of our cells, and attach to it in a way that tricks our cell to think it’s a friendly, even necessary item, and bring it inside the cell.  Once inside, the game is over, the cell is doomed, the virus wins.

So every virus has proteins coating its genetic codes that attach to very, very specific proteins on the surface of our cells.   That specific protein on the surface of our cell, then, is the keyhole that allows each virus to pick our locks.

For the SARS-CoV-2 virus, the protein on our cells it has to attach to is called the ACE-2 receptor.   Find out where the ACE-2 receptor is, and you will know where the virus will attack and destroy.

The ACE-2 Receptor, the Target Protein of the SARS-CoV-2 virus

What does the protein, the ACES-2 receptor do, when it’s not being sought out by a SARS-CoV-2 virus?  It turns out it is part of a beautiful system to manage our blood pressure and blood flow.  Our body maintains its flow of blood with a steady pressure to keep the flow steady by keeping tabs on how full the system, the blood vessels and heart.  Our body knows if there is too much or too little fluid flowing, and adjusts accordingly.

It can tell how the system is working by sensing how full every blood vessel is, how full the heart is, and how snug the fluid levels in the tiny capillaries of the lung are, where that fluid level has to be set so carefully to allow air to flow in and out of the tiny capillaries and the air sacs they cover.

Too much fluid in our lungs, heart, and blood vessels, and our kidneys pee out some more urine and our brains send out signals to not want to drink any fluid.  Too little fluid, and our kidneys pee out less urine and our brains notice and spark thirst, both increase fluid levels.

One of the main hormones that manage this delicate fine tuning is called angiotensin, and ACE-2 is  involved in helping angiotensin work (it stands for Angiotensin Converting Enzyme 2).   The ACE-2 receptor, in turn, is a protein that normally is the landing pad for that ACE-2 molecule, and when it lands, the cell knows the ACE-2 has arrived to help the body fine tune its fluid balances, and the receptor molecule is activated to bring the ACE-2 molecule into the cell to do it work.

And so, if the virus happens to attach to the ACE-2 receptor, the cell thinks an ACE-2 hormone has arrived to make a vital adjustment and brings the virus in.   Just what the virus is designed to make happen.

Where Does the Body Place its ACE-2 Receptors?

It turns out not every cell has an ACE-2 receptor on its surface, because not every organ is involved in fine tuning fluid balance.

As you might guess from the above discussion, the ACE-2 receptor is on the surface of cells in organs involved in fluid balance and blood pressure management.

We now know those cells are in the lung in cells near where the cells of our lung come close to the cells of the capillaries that coat our lung’s air sacs, on our heart cells, on the cells that form our blood vessels, on cells of our intestines, and on the cells of many parts of our brains.

Knowing Which Cells the ACE-2 Receptor is Found Gives Us Clues on How COVID-19 Makes Us Sick

Remember that a virus will land and infect cells where its target protein, its landing pads, are found.

So knowing that the ACE-2 Receptor is on the cells of lungs, hearts, guts, and even our blood vessels themselves, it is more understandable why COVID-19 is now well known to cause the following:

  • Lung failure- because the ACE-2 receptor is on lung cells leading to lung damage
  • Heart failure- because the ACE-2 receptor is on lung cells leading to heart damage
  • Vasculitis and clotting- because the ACE-2 receptor is on the actual cells that form our arteries and veins, leading to inflammation of blood vessels throughout the body (vasculitis) an disorders of clotting leading to DVT’s, pulmonary emboli, and strokes.  In children, vasculitis is responsible for the rare but serious appearance of Kawasaki-like syndrome and even severe loss of blood pressure (stroke)
  • Irritation and damage to the brain-  because the ACE-2 receptor is on brain cells, it can cause a wide variety of neurologic problems, including loss of smell and taste, headaches, profound fatigue, and at worst, actual meningitis (damaging destruction by infection of the brain)
  • Gut and liver damage- because the ACE-2 receptor is on intestinal cells and liver cells leading to damage to the gut including death of segments of the gut
  • Kidney failure- this may be the result of blood vessel inflammation in the kidney, but can lead to needing dialysis
  • Sudden death- All the above harms are clearly related to the shocking rise in the incidence of sudden, unexplained deaths

COVID-19:  From Pneumonia to Total Body Harm

When COVID-19 first appeared, the sense was that it’s worst, and primary harm, was that it could destroy the lungs.

That was true then.  Today, it still is the case that this disease can destroy the lungs.

But every month since the first case was described on November 17, 2019, we see reports from doctors and nurses caring for people with COVID-19 of new ways in which the infection harms us.  The list of harms above gives a current tally of just how much more damage this disease can cause.  The newest harm the disease causes is the emergence of inflammation of the blood vessels, in young children.  This is the vasculitis that is being referred to as having parallels to Kawasaki’s syndrome and to toxic shock syndrome, and has been given the awkward name PMIS (Pediatric Multi-System Inflammatory Syndrome).  I think a plainer title such as Pediatrics COVID-19 Vasculitis or PCV, would have been clearer, but for now we the name remains PMIS.

This review demonstrates that the crushing development that this infection not only can damage lungs so severely, but also our minds, our kidneys, our livers, our guts, our hearts, and our blood vessels with clots is not so surprising when we look at where the target of the virus, which happens to be this ACE-2 receptor, occurs on our cells:  pretty much on all these organs and blood vessels.

What New Harms Will We Learn?

As most know, accuracy drops when we move from describing what has happened to guessing what will.  Still, I do remain concerned that we will find people with COVID-19 suffer more problems than we are fully aware of.  This is in the nature of a new germ and its infections, it simply takes a long, long time to really observe, to see, all the different ways the infection can cause harm.  Further, no one has ever talked to or examined a person who had COVID-19 a year ago, it only began to exist 5 months ago in humans.  So we have no idea what long-term problems, if any, may appear after recovery.

BOTTOM LINES

  1. There are some extremely helpful websites that can give everyone a very clear look at how the virus, and how each nation, and each state, and each category of people, are doing.  The list is above.
  2. If you think COVID-19 is a disease that seems to be causing more and different harms every week, it is not your imagination.  Once thought to be primarily a disease of the lungs, we now know it can inflict real damage across the entire body.  Much of this harm follows the distribution of the protein this virus seeks, its target for entry to our cells.  Wherever this protein sits on our cells, those organs can be hurt.
  3. The range of harm now extends from lungs, to liver and gut, all our blood vessels and clots in them, brain, kidney, heart.  The inflammation of blood vessels, aka vasculitis, is now even seen in children, the first instance of serious COVID-19 illness in our children, fortunately still rare.

Time and again, we are reminded that new infections tell us more about the danger they present over time.  This new coronavirus is dangerous, it is now clear it is more dangerous than we first thought.  There is no question it is wise to find paths to avoid getting this disease.

To your health,
Dr. Arthur Lavin

 

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