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COVID-19 Update November 23, 2020: A COVID-19 Primer – On Testing and On Isolation

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
  • Symptoms- the experience of being ill, for example- fever, cough, headaches, loss of smell etc.
    • Asymptomatic– literally means “without symptoms”.  For COVID-19 it refers a person infected with the virus but has no and will have not symptoms
    • Presymptomatic– This is a person who was infected with SARS-CoV-2, and will feel sick, but hasn’t yet
  • 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.

 

A COVID-19 PRIMER

The reality of a Pandemic let loose continues to worsen and threaten.

One of the few items of information we have available to help guide is the COVID-19 test.

The test offers the hope of answering a fundamental question, do I, or someone I care for, have COVID-19 or not?

And one of the only steps we can take to slow or stop the spread of this potentially deadly virus is to isolate it if we might have the virus.

So we offer this Primer on Tests and on Isolation.

A COVID-19 Primer on Tests

Tests are confusing, some work, some do not.  Some are reliable for this situation and some for that one.

But at its heart the whole story of testing for COVID-19 is very simple, it asks only one question: “Do I have COVID-19?”

To understand how the various tests perform in answering this question, here is a guide.

Some basics.

What is tested?  Every test can only test for the presence of one thing.  Maybe it’s for the presence of a gene from the virus, or a protein from the virus, or an antibody you make in response to the virus.  But in essence, any test for COVID-19 tries to find out, is that one thing it is looking for there?

Success and failure for a test?  Imagine you are looking for a car key in your home.   You look on the kitchen counter and don’t see it.   That could mean you didn’t find it there because it was not there, or did not find it even though it was there but you didn’t happen to see it anyway.   Looking for you key is a test, it is the looking for the key test.

As silly as it sounds, that is how all tests work, they look and either find what they are looking for or not, and are either correct or not.

With these basics in mind it will be simpler to understand the ways in which a test can succeed or fail:

  1. True positive.   A true positive happens when the test claims it found what it was looking for, and in fact, that thing was present.
  2. False positive.   A false positive happens when the test claims it found what it was looking for, but  in fact, that thing was present.
  3. True negative.  A true negative happens when the test looks for but cannot find what it was looking for because that item was truly not present.
  4.  False negative. A false negative happens when the test looks for but cannot find what it was looking for even thought that item was indeed present.

Now, let’s look at the tests.

THE PCR SWAB.  

How it Works

The PCR swab is by far the most widely used test.   What this test is looking for is a bit of RNA, or genetic material, that is unique to the SARS-CoV-2 virus.  No other living thing has this sequence of RNA, so it cannot be found in any other virus or cell.

The way it works is that if the test finds a tiny bit, even a molecule or so, of the viral RNA, it makes a ton of copies, so many copies, the test can see the viral RNA by a chemical reaction.

We swab for the simple reason that the virus and its RNA dwell in the nose and throat, so swabbing is an attempt to scoop up some virus and its RNA.

What Does a Positive PCR Swab Mean?

By its very nature, a positive PCR swab is a very good sign that you have COVID-19.  Almost all positives, in a highly reliable PCR lab, are true positives.  Think about it, if the technique is right, and so RNA for the SARS-CoV-2 virus is only said to be present if the test finds it, not because of a faulty test technique, then how else could the test be positive?

Highly reliable labs are all around us for the PCR swab, especially if the lab takes some hours to do the testing.  These include the lab we use at Advanced Pediatrics, the labs at the major hospitals and lab chains.

One exception are some of the 15 minute rapid PCR test techniques, such as the Abbot ID Now platform, whose positives are too frequently false.  (NOTE:  This has been the platform used in the White House).

So, if you get a PCR swab done in our office, a hospital, or reputable lab, and it is positive, you almost certainly have COVID-19.

What Does a Negative PCR Swab Mean?

Not as much as a positive.

The swab could be negative even though you have COVID-19 for two big reasons:

  1. You might be swabbed too soon after getting infected.  It takes about 300 viruses to land on your eyes, nose, or mouth to get COVID-19.  But if you have only 300 in your nose, a swab could miss them easily.  After about 5 days of being infected, those 300 turn into zillions, and now each breath might exhale 750,000 of these viruses.  So if you get infected on January 1, and then swab on January 2, you have a 100% chance of a false negative.   If you wait from day 5, to January 5, your false negative rate drops to well below 20%.
  2. The swab may simply miss picking up the virus.  You might have loads of SARS-CoV-2 virus in your nose and mouth, but the swab simply misses picking them up.  This is why even after 5 days of being infected, your test for COVID-19 may just happen to turn out negative.

The Antigen Test

This is the famous saliva test, rapid, cheap, should be widely available one day.  This is a test you can do at home and the result looks like a pregnancy test, a strip either turns color or not.

How Does it Work?

The word antigen is a fancy word for the chemical in a germ that alerts our immune system, usually a protein.  The COVID-19 antigen tests look for proteins only found on the surface of the SARS-CoV-2 test.   Remember every virus is essentially a bit of genes wrapped in a coat of protein.  If the PCR swab looks for that bit of gene, the protein test looks for a protein in the viral coat of protein.  Each virus has a unique few proteins in the coat of protein.

What Does a Positive Antigen Test Mean?

Again, a positive test usually means you have COVID-19.  After all, if the test finds a protein unique to the SARS-CoV-2 virus, it usually means the virus is there, which means you are infected.

And current antigen tests, like the PCR swab, have a very low false positive rate, so if your antigen test is positive, you likely have COVID-19.

It does not sound like much, but the antigen tests tend to run false positive rates of 2-3%.  This means about 2-3% of everyone not infected tested with this test will come out positive.

If we deploy the antigen test widely, and it makes good sense to do so, then say if 100 million people who are not infected do the test, about 2-3 million people will be told they have COVID-19, when they do not.

This is why we do not use the antigen test in our office, and most testing centers that really need to know if you have COVID-19 do not.

But this flaw essentially disappears with repeated use.  After all, say you are someone without COVID-19, and you do the antigen test 100 times, you will be positive twice, but true negative 98 times.  So over a bunch of tests the trend of not being positive will overwhelmingly prevail.

That means the antigen test, as currently developed, can be very useful in mass testing strategies, where say I might test myself every day, and maybe 5 or 10 times if positive.  Repeated tests will reveal the false positive.

What does a Negative Antigen Test Mean?

Essentially the same as a negative PCR test, so see above.

Antibody Tests

This is the only blood test on this list.  It takes blood and tries to see if you were ever infected with COVID-19.

How does the Antibody Test Work?

An antibody is a very special protein that is designed to attach to one and only one alien protein.  Our protein, the antibody, is built to “recognize” an alien protein.  Because it can only attach to that one alien protein, when it does, it can reliably send in the army of the immune system to destroy the detected germ.

In this instance the antibody the test is looking for is an antibody to the protein that forms all those spikes that cover the coronavirus in a crown (hence, corona-).

If you have an antibody to that spike protein, called the S protein of the SARS-CoV-2 virus, or S for short, you had COVID-19.  There is no other way you could have that particular antibody.

The Problem with Antibody Tests

There is a BIG problem with the antibody tests being done in the US.  Under pressure to act, the FDA released nearly 200 different brands of COVID Antibody tests in the US.  Reliable evaluations reveal that most of them are simply terrible.

Most have 49% false positive AND 49% false negative rates, which means whatever your test result, this test will be wrong at least half the time.

In speaking with those evaluating various brands I am told that even now, there is no reliable way to know if the antibody test result you receive is correct.

Further, antibody levels change, even with a reliable test, you might test before your antibody develops or after it fades.

A COVID-19 PRIMER ON ISOLATION

Like tests, the basic point here is simple.  For tests the basic point is that tests all are looking for something.

For isolation the basic point is that we are all trying to keep the virus from spreading and killing or hurting someone.  That’s it.

Now, to stop the virus from spreading, the point is very simple too.  Make sure anyone who is contagious does not come near to anyone who is not infected.  That’s it.

The essence of stopping this virus from spreading, therefore, is trying to figure who is contagious and keep them away from everyone, until they are not contagious.

As a result, every guidance on isolation does just that, and depends on knowing when someone is contagious and when someone is not.  Contagious- isolate.  Not contagious- do not isolate.

Who is Contagious?

A few simple facts can help us answer this question.

  1. You have to be infected with COVID-19 to be contagious.  No COVID-19, no contagion.
  2. Once infected with COVID-19, you are only contagious for a specific period.  After that time, even though you were infected, you are no longer contagious.
  3. You can be very contagious with NO symptoms at all.  It takes about 300 viruses to land on you to get infected, and once contagious, you blow out close to a million with every breath, even if you feel great!
  4. If you are contagious, you can spread it even with a mask on.  Masks help, they drop the chance of spread by 50-80% and can save hundreds of thousands of lives.  But if you are contagious, nothing beats just staying away from everyone to stop the spread.

With this all in mind, let’s see when people with COVID-19 are contagious.

Basically, from the first day of being infected, a person can be contagious up to about 14 days after.

So, if someone got infected with COVID-19 on January 1, they would be contagious up to through January 14, and not be contagious January 15.

Symptoms are different from contagion as noted above.  So if you have no symptoms, you still might be infected and contagious.

But if you develop symptoms with your COVID-19, you get to have something those infected with no symptoms cannot have- a clock.

Without symptoms, who knows when you got infected.  But with symptoms you can use these facts to know when you got infected, and when you are contagious:

  1. It takes about 5 days to get symptoms from COVID-19.
  2. A person with COVID-19 symptoms knows they are contagious from 2 days before the first symptom through the 10th day after the 1st symptom.

For our person with COVID-19 who got infected on January 1, they will typically start being contagious on January 3, have first symptoms on January 5, and cease being contagious on January 15.

Various testing scenarios and how they define how long to be in isolation

A person tests positive with COVID-19 but has no symptoms.

If the test is a reliable PCR test, then the chances are overwhelming that this person is infected with COVID-19.   This means the person is almost certain to be contagious at some time, but we cannot know when.  The possibility is that the person is contagious as early as the day of the test, might be contagious any day through the next 14 days following the test.

And so, in this scenario, to avoid spreading a potentially deadly virus, this person needs to be in isolation from the day of the test through 14 days.  If the test was done January 1, the person needs to be in isolation through January 14, and out of isolation January 15.

A person tests positive with COVID-19 and does have symptoms.

If the test is a reliable PCR test, then the chances are overwhelming that this person is infected with COVID-19.   This means the person, with symptoms is almost certain to be contagious.  The symptoms give this person a clock of their contagion, which began 2 days before the first symptom and lasts through 10 days following the first symptom.

And so, in this scenario, to avoid spreading a potentially deadly virus, this person needs to be in isolation from the first day of symptoms through the 10th day of symptoms.   If the first symptom was on January 3, then the person became contagious on January 1 and will remain contagious through January 14.  Therefore, the person needs to be in isolation through January 14, and out of isolation January 15.

A person with symptoms of a viral infection tests negative for COVID-19 and has no known contact with a person with a positive test.

Despite the many false negatives of COVID-19 testing, this person is most likely not to have COVID-19, and so the combination of a negative test and lack of known contacts means they are not likely to be contagious for COVID-19.  This person does not need to be in isolation to prevent the spread of COVID-19.

A Word on the Contagion Question for Direct Contacts

A direct contact is anyone who has been within 6 feet of a person known to be tested positive for COVID-19 for more than a few seconds, technically for 15 minutes or more, but really could be just  a few minutes.  If anyone is in direct contact, they can catch the virus, and if they catch the virus, they will certainly become contagious, and can pass it along to others, putting lives at risk.

The trouble with direct contacts is that they can occur over and over and over again with the same contagious person.  Take the example of Person A who tests positive for COVID-19 on January 5, and had their first symptom on January 5.  This Person A likely got infected on January 1.  And then became contagious on January 3.   And became contagious, as we have seen, from January 3  through January 13.  That means anyone who comes close to Person A at anytime, January 1 can get COVID-19 from Person A.   This is also true if the contact is on January 2.  Or January 3. Or January 4.  Or January 5.  Or January 6. Or January 7. Or January 8.  Or January 9. Or January 10.  Or January 11. Or January 12.  Or even January 13.  But by January 14, Person A will no longer be contagious.

And so, even with no further testing, Person A will no longer need to be isolated on January 14 or beyond.

But here is the main point on direct contacts.   If I live with a child with COVID-19, and that person has the time line for Person A above, I can come down with COVID-19 from my contact with my child on a large number of days. And if I come down with COVID-19, I have to be isolated until I am no longer contagious.   Because, in this example, I might not catch COVID-19 until as late as Person A’s last day of contagion, January 13, my time of isolation as a direct contact must begin on the FIRST day of my exposure and extend a full 14 days past the LAST day of contact with a contagious person.

Otherwise I could spread a deadly virus.

Now, back to more scenarios:

A person in contact with a person know to have a positive COVID-19 test has a positive COVID-19 test.

In this scenario the person has a positive COVID-19 test and so as noted above almost certainly infected with COVID-19 and their situation is the same as the person with a positive COVID-19 test described above, so the advice would be the same.  Which is to say, this person will be contagious for COVID-19 and must take steps not to spread this potentially deadly virus.  Knowing what days this person could be contagious depends on the date of the test, and the presence of absence of symptoms.

The difference here is that this person has had a known contact and so might come down with COVID-19 from this contact, and become contagious.  So this person must remain isolated at least 14 days from the date of their last contact as noted above.

A person in contact with a person know to have a positive COVID-19 test has a negative COVID-19 test.

You might guess from all the above that this person’s negative COVID-19 test does not prove that this person did not get COVID for there possible reasons:

  1. It might mean this person avoided infection from the direct contact.
  2. Or it might be negative because the test was done in that interval between getting infected and the virus rising up in loads large enough to be detected.
  3. Or it might be negative even though the direct contact is highly infected, actively contagious, and simply got a false negative result.

It is for all these reasons that when one tests a direct contact, a negative result does not end that contact’s risk of being a contagious spreader of COVID-19.  And therefore, in this instance, the direct contact must remain in isolation starting on the FIRST day of exposure to the person known to have a positive test, and extend a full 14 days past the LAST day of contact with this direct contact while they are a contagious person.

BOTTOM LINES

  1. Testing is all about looking for a particular item.  That item may or may not, in reality, at that moment, be present.  And the test may or may not report the test found it.
  2. The PCR swab searches for a bit of genetic material of the SARS-CoV-2 virus.  If it reports it found it, it almost certainly did.   False positives of the PCR swab are very unusual.   But the swab can easily miss picking up on the genetic material.  Overall, 20% of PCR swabs that are reported negative are actually false, that is the person is actually infected.
  3. Isolation, or quarantine, is at its heart, an attempt to keep people who might be contagious from spreading the possibly deadly disease to other.
  4. Who should be considered contagious, and therefore urgently need to be isolated until no longer contagious?
    1. People with positive COVID-19 PCR swabs
    2. People who have been in contact with positive COVID-19 PCR swabs while such positives are contagious.
  5. How long are people who might be contagious for COVID-19 be contagious?
    1. For those not in a hospital, the risk of contagion is over after 14 days at most.
    2. Contagion typically begins 2 days before symptoms occur, and ends after the 10th day after the first day of symptoms.
    3. Perhaps the longest stretch of suspecting one may be contagious comes to the person in ongoing contact with someone known to be contagious.  Think of a person contagious for 14 days.  That means if someone is living with that contagious person, they can catch COVID-19 on any of those 14 days, so their isolation must start, at the earliest, on the first day of contact; and start, at the latest on the last day of their contact while that person is contagious.

My Takeaway – In One Sentence

Tests search for specific proof of COVID-19, and isolation seeks to end the spread of it, knowing how both work can help you understand how to find if you are infected and when to be isolated, both essential to keeping this danger from coming to you and those you love.

To your health,
Dr. Arthur Lavin

 

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