COVID-19 update with Dr. Benjamin Marcum

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Myth 7: We are not at war.

Since the beginning, there has raged a biological arms race inside of every living thing.  Organisms utilize their unique biological processes to grow and flourish, taking nutrients from outside of themselves and restructuring them in to DNA and proteins and cells and organs and appendages.  Other organisms have long sought to co-opt those biologic processes for their own propagation.  Such is the modus operandi of a virus.

Today I want to share with you the story of what happens to the human body when it is infected by SARS CoV-2 – the virus that causes the disease named COVID-19.  This story is meant to inform and encourage because for the most part, the arms race tips in our favor.  A small minority of patients who are somehow otherwise compromised will lose the fight.  These are the people we must protect by informing ourselves and limiting the spread.  I must admit that my undergraduate degree from Baylor (Sic ’em) is in biochemistry so molecular biology and immunology set my brain to hummin’.  I will do my best to tell this story without indulging in too much science speak, so hang in there with me.  If anything is unclear, please don’t hesitate to comment and I’ll see if I can clear it up. 

Step 1. Infection

An infected person, who may or may not yet have symptoms, is producing thousands to millions of copies of the virus in their nose and pharynx (the connection between nose and throat).  The virus is shedding everywhere, on their hands, their face, their clothes.  They enter a place of business after absentmindedly scratching an irritation on their face and put their bare (or gloved, for that matter) hand on the door handle to the business.  Five minutes later, you enter, putting your hand on the same surface.  Your hand comes in contact with several thousand copies of the virus.  A few minutes later your eye itches and you rub it.  You are now infected.  This is one possible mode of infection.  For the most part people are infected after they spend more than 15 to 30 minutes in the same space with someone who is shedding virus.  The major mode of transmission is through respiratory droplets – these are microscopic drops of fluid that are expelled when someone coughs or sneezes and in the case of a person infected with SARS CoV-2, they are loaded with virus.  These droplets deposit on surfaces that are then touched by unsuspecting others and the virus is transmitted.  Droplets do not travel more than 6 feet and do not linger in the air.  This is why we have asked everyone to stay 6 feet away because respiratory droplets are expelled even when talking.  

There is debate amongst the scientific community as to whether the virus is airborne.  Airborne transmission means that it is transferred in aerosols smaller than 5 micrometers (the virus is measured in nanometers, about 200 at the largest) that don’t fall out of the air due to gravity.  They are just floating around waiting for someone to inhale.  We can’t definitively say that this virus is transferred this way but we also can’t definitively say it’s not which is why we wear N95 masks and face-shields when caring for patients with COVID-19, especially if there is going to be an aerosol producing procedure like intubation.  We also try to avoid using BiPAP (a mask that blows pressurized air into the lungs without a breathing tube) because it produces lots of aerosols.  For more information on whether the virus is airborne or not, here is an interesting article: 
https://www.nature.com/articles/d41586-020-00974-w

It is not known exactly how many copies of the virus are necessary to cause infection.  You won’t get infected if you are exposed to 1 or 10 but maybe a few hundred or 1000.  Based on the rate of spread the infectious dose is likely in the 100s to 1000s which is not very many in virus world.  There is also no evidence that you do worse if you are exposed to more copies or not.  We also don’t know how soon after exposure you are typically shedding virus.  The studies we have used so far to assess this look for viral RNA in nasal secretions but just because RNA is there does not necessarily mean you are infectious.  Also, we don’t know for sure how long you are infectious.  One study found RNA in the oropharynx ceased at an average of 20 days after exposure (range of 8-37 days).  So viral RNA expression is variable.  It seems that when people are feeling better, there is very little RNA shedding going on.  This is why the CDC has set 2 criteria for going back to work.  Either no fever and improvement of symptoms for 3 days or 2 negative tests.  Obviously we would all prefer 2 negative tests on every person but since we have limited numbers of tests we can’t feasibly do that.  

Step 2: Incubation

Here is where the arms race gets interesting.  Once the virus has breached your body’s defenses, it goes to work.  It’s entire goal, its reason for existence, is to use your cellular machinery to make more copies of itself and spread somewhere else.  The virus membrane comes into contact with your cell and fuses with the cell.  Then all the contents of the virus are now inside your host cell.  This is where, as one of my friends put it, we see the virus’ narcissistic nature.  Inside of all our cells we have molecular machines called ribosomes. Ribosomes are used to read RNA and build the proteins that are encoded in the strand of RNA.  The virus’ RNA strand muscles its way to the ribosome and demands that it start producing the proteins it wants produced and not your own cell’s proteins.  And once it has hold of the ribosome, the replication continues over and over until many copies of the virus have been created and assembled using other host cellular machinery inside the cell.  The baby viruses then exit the cell, leaving it intact.  Some coronavirinae cause many cells to fuse creating one large super cell whose only function is to make baby viruses.  Causing this fusion helps the virus hide from the immune system.  This process begins with infection and continues for up to 14 days (hence the 14 day quarantines) before symptoms develop.  In some patients, symptoms never develop and the immune system recognizes and eliminates the virus without illness.  In most, some symptoms will develop within 4-5 days of infection.  Virus has been detected in large levels in the nasopharynx of people before symptoms develop which is one of the reasons this virus has so aptly spread among us.  

I want to take this opportunity to address ace inhibitors and angiotensin receptor blockers.  Many of you know or have read that the virus attaches to the ACE-2 receptor on human cells and that is how it enters the cell.  Some have hypothesized that taking medications that block the activity of ACE receptors to help control BP might upregulate those receptors and make you more susceptible to infection.  The theory makes sense so some have asked whether they should stop their medicine.  The answer is absolutely not.  This has been studied and there is an official recommendation from public health authorities not to stop the ACE inhibitor or ARB.  If you stop it, your blood pressure will likely rise or your heart disease will get worse.  This is much more likely to cause a bad outcome if you develop COVID-19 than if you continue to take the med.  As always, discuss any medication changes with your physician before you make the change.  You may cause more harm that you think if you change them without consultation. 

Step 3: Illness

The medical term for how something makes you sick is pathogensis.  The pathogenisis of Covid-19 is not well understood – again, baby science.  But we have some ideas.  The genome of the virus that causes COVID-19 is not very different from the coronavirinae that cause SARS and MEARS.  So we can infer some of what to expect from our experience with those viruses.  But clearly this virus has about 30% new genetic material that no human body had ever faced before December of 2019.  Our lack of any immune protection from this virus in humans has allowed it to gain a strong global foothold and cause devastating illness in about 5% of those it infects.  
A clear picture of what happens in COVID-19 has emerged.  Lungs sound clear on exam but appear to have bilateral pneumonia in both lungs on CT scan.  Lymphocytes (one type of white blood cell important in immune function) are low.  Patients have a dry cough, fever, body aches and even many reports of loss of taste and smell, possibly implicating some nerve involvement.  (A couple of nerves coming from your spinal cord are responsible for those senses).  These symptoms occur because your immune system is activated.  Specific cells in your immune system recognize that there is a foreign object furtively traveling from cell to cell implicit in nefarious behavior and all the bells and sirens go off.  The biological war is on.  Your immune system works by emitting inflammatory substances at the site of injury or infection to kill the offending agent while trying to preserve your own tissue and promote healing.  Inflammation is the hallmark of immune system activity.  When you get a cut on your finger, it often hurts much worse a day or two after the actual injury.  This is because of inflammation, the immune system has released proteins that cause complex chemical reactions and illicit a pain response at the site of injury.  The pain you feel when you bump that injured site reminds you not to bump it – it’s trying to heal.  It also is evidence of immune activity trying to prevent an infection at the site of laceration.  It also swells.  For those of you that have kids at home and have watched Finding Nemo recently, Nemo’s dad, Marlin, says to him after he supposedly had an injury, “Sometimes fluids rush to the area, any rushing fluids?”  This parody of an overprotective parent contains a seed of truth.  Where there is inflammation, there is fluid.  And that is a large part of what ultimately causes respiratory failure in very sick patients with COVID-19.  
The earliest reports of this disease revealed that 81 percent of people (that’s 4 out of 5) have either no pneumonia or only a very mild case.  This is fantastic news!  Severe disease presents in 14%.  That is greater than 50% lung involvement after 24-48 hours.  Critical disease (respiratory failure, shock or multi-organ dysfunction) is present in 5%.  2.3% of infected individuals die.  This is data from 44,000 cases out of China.  The death rate in the US is similar.  Death happens by far in most cases due to what is called a cytokine storm.  For whatever reason, an immune system inflammatory protein named interleukin-6 (along with many other mediators but this seems to be one of the main ones) is produced in an uncontrolled amount around day 7-10 of illness and what follows is Acute Respiratory Distress Syndrome due to out of control immune mediated inflammation.  This is an acute decompensation of lung function that is heralded by the alveoli (tiny air sacs in the lungs) filling up with fluid.  Your lungs are like a dry sponge, expanding and contracting with every breath.  Each tiny air pocket is lined with membranes containing blood vessels that exchange O2 and CO2 with every inhalation and exhalation.  That air pocket must be open for that exchange to occur.  When a patient experiences ARDS it’s as if someone took that sponge and dipped it in a bucket of water, filling the alveoli with fluid and severely limiting that gas exchange.  This happens because viral activity has become so high that the immune system begins to act with reckless abandon, doing what it can to kill the virus at the expense of the host tissues as well.

Two internal wars threaten us.  One is the potential biological war with SARS CoV-2 we will face if we develop COVID-19.  Our immune system will fight that one on our behalf but we must do what we can to help it.  Practice good nutrition, control chronic medical conditions, take medications as prescribed.  The second war is the psychological conflict we all must face whether we become infected or not.  We must battle our own personal agendas, our own pride, and put the needs of our most vulnerable neighbors above our own.  Self preservation and self service are strong currents running through each of our human natures.  Altruism and benevolence can run equally as strong.  We must fight to look beyond ourselves and sacrifice to limit the chances this virus has to spread.  As modern medicine advances, the arms race we have been fighting for centuries continues to tip in our favor.  Today, our most powerful weapon against SARS CoV-2 is knowledge of what the virus can do, how it can spread and how we can stop it in its tracks.  

Enjoy your weekend home with your loved ones.  Wash your hands.
BAM

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