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COVID-19 Update May 1, 2020: Vasculitis in Children, Remdesivir

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

The SARS-CoV-2 virus spreads, spreads easily, spreads explosively.  Four events remind us of this essential nature of this virus that causes COVID-19.

Community Gatherings.  Over and over and over again, around the world, clearly in the US, in many, many states, you gather, and COVID-19 flares.  It happened when voters were forced to gather to vote in person in Wisconsin, it has happened in various protest rallies against gathering, ironically enough.  You can count on it.

Nursing homes.   Place people into close proximity and unable to move out of harm’s way, and you will get intense outbreaks.  About 20% of all deaths from COVID-19 in the US are from out of control outbreaks in our nursing homes, around the country.

Prisons  Place people into close proximity and unable to move out of harm’s way, and you will get intense outbreaks.  The largest single number of infected people with COVID-19 in the United States, and one of the largest in the world, is in Marion,Ohio, in an Ohio prison there.  This in a state that has had a relatively well-controlled outbreak.

Factories  Place people into close proximity and unable to move out of harm’s way, and you will get intense outbreaks.   A rampant epidemic of COVID-19 is happening in a series of meat-packing plants, each of which share the features of being huge, with thousands of workers standing elbow to elbow all day.

The problem with each of these examples, is that the SARS-CoV-2 virus truly is very, very, very contagious, let it run, and it will run, not just in the spot where gathering allowed it to burn, but across the entire community.  We have seen just this happen in every one of these four settings.  Take prisons and factories for example, in both cases, rampant infection in the prison and in the factory led to whole communities seeing surges that overwhelm their hospitals.

Severity

A serious problem from infection with the SARS-CoV-2 virus appears in children, but is very, very rare:  Vasculitis

Some preliminary reports are describing the appearance of inflamed blood vessels from COVID-19, mainly in children, in a pattern of inflammation known as vasculitis.

To understand vasculitis, it helps to think about the blood vessels of the body as living tubes, not like plastic tubes.  Every artery, vein, and capillary is made up of living cells, that shape and connect to each other in forms that create hollow tubes, the hollow tubes all our blood flows around.    In order to keep leaks from happening, these cells overlap, and maintain a leak-free connection by that overlap, and judicious use of clotting as needed.

Inflammation is a familiar phenomenon, to anyone who has had a mosquito bite.  Inflammation is the name for when our immune system attacks a spot in our body to rid itself of an invading germ, abnormal cell, or unfamiliar chemical.  When the attack is triggered, cells and chemicals from our immune system gather to neutralize the enemy.  When they all gather, the area usually turns red, gets warm, swells larger, and hurts or itches.  All these things happen with mosquito bites, and all these things happen with most inflammation, with one additional event- loss of function.  We see loss of function in arthritis where the inflammation gets in the way of the joint working.

When a part of the body gets inflamed, we say it is an xxxx-itis.  The -itis simply means inflamed.  So appendicitis is inflammation of the appendix.  Pharyngitis is inflammation of the pharynx, or throat.  And vasculitis is inflammation of the blood vessels.

Any area of the body can get inflamed, including those blood vessels we just described as tubes of living cells.  When vasculitis happens in blood vessels near the skin, a rash will appear.  Vasculitis of other blood vessels can damage the organs those blood vessels feed.  So vasculitis of blood vessels serving the heart can endanger the heart.  If enough blood vessels get inflamed, it gets harder to push the blood around, and blood pressure drops.  Inflammation of the cells of the blood vessels can interfere with how these cells control clotting, leading to less clotting than needed or leaky vessels, or to more clotting than needed or blood clots.

So, vasculitis can cause a very wide-range of troubles, some as mild as a rash, some far more serious.

And therefore, it was very disturbing to hear these preliminary reports that COVID-19 infection was now seen, still very, very rarely, causing vasculitis in children.  The reports were a bt short on details, but from what I can gather, the pattern of vasculitis seen was severe, including dangerous drops in blood pressure, high fevers, and threats to heart function.

The report refers to two far better described patterns of vasculitis- toxic shock syndrome (TSS), and Kawasaki’s syndrome (KS).

This rare COVID-19 vasculitis in children is not TSS and it is not KS.  TSS is a syndrome where a bacteria, usually a type of Staph, creates chemicals (toxic) that sicken the blood vessels, causing terrible fevers, and collapse of the blood presssure (shock).  KS is a syndrome where  wide range of blood vessels suffer grievous inflammation, causing red rash of eyes, skin, lips; large lymph nodes, high fevers, and weakened coronary arteries that can then form aneurysms.   The report suggests that COVID-19 vasculitis cases seen have the high fever, loss of blood pressure, and some vaguely described weakening of the heart.

Two well-known COVID-19 phenomenon might be related to vasculitis, too:

  1. COVID toes.  This is a now well-described event where the top surface of usually a few toes turns purple, not painful usually.  This could reflect inflammation of the small blood vessels in the skin.
  2. Clotting in adults.  We have noted this development for some time in Real Answers, it is the tragic development of clots in the legs (DVTs), in the lungs (pulmonary emboli, or in the brain (strokes).  No one knows why having COVID-19 makes clots form, but they do in some with this disease.  It might be that vasculitis is the root cause here too.

COVID-19 is turning out to be a disease of increasing possible bad outcomes

This point has been explored in detail in prior posts of Real Answers, but now that we are seeing children presenting with very serious dangers from vasculitis, it needs to be observed again and again, that this virus continues to devise new ways to torment us and endanger our lives.

It began as simply a lung infection.  But now it is also a heart infection, a brain infection, a liver infection, a kidney infection, and a blood vessel infection.

I was deeply moved by the repeated testimonies of ICU nurses who have worked in ICUs for 10-20 years, and have stated, they have never seen so many people this extremely ill ever before.

All this says to me that this virus is truly dangerous.  I am thrilled that so many infected have no symptoms or are only mildly ill, thrilled.  But do not be deceived, the other deep truth about COVID-19 is that it can cause horrible, horrible damage to any adult, and rarely, child.

Treatment

Remdesivir

A dramatic announcement was made by Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID) from the Oval Office.

The drama had to with some early indications, that there may be a drug that helps treat COVID-19.

The name of the drug is remdesivir, which was briefly described some time ago in Real Answers.  To recap, any drug that ends with the three letters, vir, is an antiviral, a drug that slows the progress of or kills a virus.

Remdesivir was developed to treat Ebola viral infections and another dread virus, the Marburg virus.   If you take remdesivir, your body metabolizes it to a molecule that seems to look like another chemical, called adenosine.   Now can you recall your memories of how DNA works?  DNA is what our genes our made out of.  And it is the code that allows our cells to know what proteins, what structures, what enzymes to make.  The information is contained in the sequence of four chemicals:  Guanine, Cytosine, Thymine, and Adenosine, which are notated by their initials:  G, C, T, A.  Like letters, these four compounds form long sequences that have much meaning.

Viruses have genes too, but theirs are made out of RNA, not DNA.  But viral RNA uses adenosine, or A, as one of its four letters too.   You may recall that what viruses do  is to basically take over a cell and force it to make tons of new viruses, by making tons of copies.  A big part of this job is to copy the viral RNA.  Well, if you take a drug like remdesivir, the idea is to have its look alike adenosine jam up the copying of the real viral RNA, which must have real RNA Adenosine in its sequences to work.

That’s the idea.  Now does it work?  https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19

Here is what we know- The study took many people with COVID-19 severe enough to be in the hospital, all of whom had lung troubles with the inFection.  A group of people with COVID-19 were given remdesivir, and a similar group were not.  They found those who did not get remdesivir were sick for 15 days, those who got it, 11 days.  They also found that those who did not get remdesivir, 11.6% died, but if you got the remdesivir, 8% died.

BOTTOM LINES

  1. COVID-19 continues to show us that it can hurt, maim, and kill us in more and more ways than we first thought.  The disease COVID-19 is getting worse every week.
  2.  Infection with the  SARS-CoV-2 virus can be mild, often is, at least 50% of those infected have no symptoms at all.
  3.  So this infection, COVID-19, has two faces.  A mild, harmless experience, or some of the worse disease seen in the most intensive disease settings, the ICU.  Both are true aspects of COVID-19
  4. COVID-19, mild or deadly, is very, very contagious.  Let a little outbreak happen, and it turns big fast.
  5. Add vasculitis in children to the list of troubles an infection with COVID-19 can bring.  Fortunately this is still a rare event.  But we need to pay attention, lately we have seen the range of trouble this virus can cause getting worse, not better.
  6. Remdesivir is designed to keep the RNA (genes) of the SARS-CoV-2 virus from copying, blocking the infection, we hope, from causing harm.  We simply do not know it this will work.  The good news is that it seems, in one study, to shorten the stay in the hospital by a few days, and reduce mortality a few percentage points.  The bad news is that this benefit is not seen in all studies, and the amount of benefit is fairly modest.  The hope is that if we found a drug that can do this, it opens the door to next drugs that will do better.  That is a fair hope, it is not a proven outcome.

Our United States is moving to believe that our national lockdown has conquered this disease, and vanquished this virus, eager to go back to work and play.  These observations prove the virus has not been vanquished, just the opposite, it remains surrounding us, and as of today we have no treatment to stop it from harming us.

Therefore, as we open our doors, we must know that outbreaks will occur, and hope that our nation has taken the steps to detect and respond and contain these outbreaks when they are small, or we will be facing huge hot spots all over again.  And how is that done?  Readers of this column know:  Testing, Contact Tracing, Isolation of as many infected as possible.

To your health,
Dr. Arthur Lavin

 

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