To Test or Not to Test? Understanding COVID-19 Testing

Mark Menolascino MD, MS

Have you had COVID-19 and not know it?  SARS CoV-2 causes a disease called COVID -19 (for Corona Virus Disease started in 2019) similar to the influenza virus causing the flu. COVID-19 has infected over 2,000,000 people with over 30,000 deaths worldwide as of April 15, 2020.  If that virus can put people in the ICU how can it infect someone, and they have no symptoms?  Who should we test?  What test should we use?  Is 6 feet far enough away?  Should I disinfect my groceries?  Is the store safe to go to without a mask? These are the details of this pandemic we are just now sorting out.  Here we are into mid-April and we know just enough to be dangerous.

How do we restart our economy and protect each other if we can’t tell if we have or have not had COVID-19 yet? Estimates are that 20-80% of people who get the virus may have no symptoms or have a very mild case.  On the opposite end, I have had clients tell me they got it and it hit them like a freight train and almost killed them!  I have heard various COVID client recovery stories ranging from only few days of mild headache compared to 2 weeks of misery with high fever, pain everywhere and hallucinations as well as long hospital stays and ventilators.  Then there are reports that people who were positive and were sick with COVID-19, then cleared it and tested negative then came back and were positive again!  Why the variability and how do we find who is safe to work?

The logical answer seems to develop testing that can tell us who is vulnerable and who is protected.  This is possible yet not easy to get right.  The testing is still a work in progress and many companies are rolling out tests without FDA approval and limited resources that is causing all testing to look marginal.  However, the idea of a noninvasive finger stick blood test or saliva test with immediate results is the holy grail needed for us to move forward – if it can accurately tell us who is safe or sick.  We have proven that home flu testing was 85% as accurate as being tested in a hospital setting so this concept is not new.

How do you understand the testing??  Well, I like things simple.  The hospital test is a direct measure of the RNA component of the virus.  The test we do as the gold standard is similar to the flu test technology.  We shove a swab up your nose and sort of down your throat- the so-called ‘nasopharyngeal swab’ and get a sample where the virus likes to live-nasal passages and throat before it moves to its favorite site the lungs. (many times, the swab only gets in the base of the nose and not deep so easily can get false negative test). Then we run that sample through a machine that reads little proteins called RNA that are only found in one place in the entire universe-a pattern only seen in that virus.  That is a definitive test but as I like to say- ‘Trust a positive, don’t dismiss a negative’ with the variation is sample area mentioned above.

No test is perfect and this one isn’t either.  If I was in the ICU and someone had classic symptoms and lung scans consistent with COVID-19  but a negative swab, I would treat them as COVID-19 but keep an open mind that it could be something else.  And I would probably retest them again due to the above sampling errors.

The antibody testing is not as straightforward.  I like to think of it like Mono-when you kiss the wrong person you get EBV or Epstein Barr virus.  When we get exposed to this virus, our body sends an immediate immune response in 2-3 days called IgM against EBV, or the ‘early infection sign’ protein as an initial sign we have the infection and that it is mounting a defense against the virus with the immune system.  Within 6-9 days, we produce another immune protein called IgG against EBV that may be present for the rest of your lives to show we have been exposed. This is the goal we are striving for in the so-called “Herd Immunity” concept.  The virus will only stop when enough of us have had the virus-our IgG then is positive and ‘protects’ us against reinfection, or we have a vaccine that protects all of us (actually about 90% of either option will squash the incredible spread).

Wow, that sounds easy, test the blood and if IgM you are sick and contagious; if you have IgG you were sick and not contagious.  Oh, I wish it was that simple……

If you have IgM or IgM/IgG positive (especially with a positive nasal swab as it is not a perfect test either as mentioned above) to COVID-19  then you are actively infected and contagious.  If you have IgG than you had COVID-19  and are now immune protected and theoretically can’t get it again and are not contagious-we think!

The best plan appears to be to combine the nasal-pharygneal RNA swab (RT-qPCR in graph below) with the IgM/IgG test and get a matrix of possibilities that will let us drill down to who really is sick, contagious, or immune-the gold standard for us to move forward.  I recommend we do all three.

So, what does any good doctor do?  Get checked out! I worked in a hospital caring for a family member in Europe during January and February of this year-only 2 months ago and feels like an eternity-and came home with a high fever, cough and muscle aches and flu-like symptoms but had a negative flu test; I did not qualify for a COVID-19 test at our local hospital as I had no other underlying health conditions and was young and strong enough and wasn’t sick enough to need to be going into the hospital and use that valuable resource needed for more at-risk patients.

The antibody tests sounded to me like the perfect solution-they tell you if you have had the virus already and are immune if your IgG is positive which is the protein for long term immunity. Wow, to have the comfort to know you already had COVID-19, beat it and are now safe from catching it again would be very helpful.  So, I was tested this week as what I wanted to really know – was that 104 degree fever and misery in February actually COVID-19?  So, I got antibody tested, and is totally negative-IgM and IgG negative- but was it actually COVID-19 …I will wait another month and test again just to be safe.

My Panel from this week: ALL NEGATIVE (this company adds IgA as this is the antibody for nasal/throat/lung tissue response)

They have tried to do this for an entire county-a similar ski town to mine of Jackson Hole- Telluride, Colorado offered to test first the town, then the entire San Miguel county to see who had been infected and who was protected and therefore identify people that could work in public without spreading the virus.  They promised to test all 8,000 residents of Telluride and then offered to the entire 20,000-person county with guaranteed results within a few days.  However, the delays in the lab, lack of reagents/chemicals and a bottleneck with the sheer overload on the lab forced the project to an end without a clear conclusion.  THEY STILL DON’T KNOW.

We are talking about doing this in our ski town here in Jackson Hole and I recommend we test all healthcare workers and first responders find out who is safe to be on their frontlines-for both the healthcare worker and for the patients and our communities.

One of my friends decided to test his entire company-Designs for Health, a nutritional supplement manufacturer offered the antibody tests for free to his entire company.  We will see more of this in the future that individuals, companies, communities may take on a challenge that local governments can’t address due to policy or unclear directives.  All of this must be gathered and used for the greater good to decide as communities and nations and as human race how we go forward to reduce the death and suffering of this pandemic.

How frustrating as so much has been with the social distancing/isolation, but we are handicapped with a lack of tools for both public and healthcare worker needs.  We can do better.

There is a theory going around that the COVID was actually in the US as early as December 2019, particularly in California and possibly here in Jackson Hole due to tourists worldwide at a low level-too low to detect as was not a true outbreak.  This seems reasonable to me as our world is open now with air travel and very possible some early travelers to and from China were in your area and mine during December-for sure on the East and West coast of the US.  However, we would have seen some very sick people with the typical lung CT scans that we are seeing now with COVID.  Yes, it is possible they weren’t scanned, or other patterns didn’t fit like a huge outbreak at that time like we had in March.

So, I live in Jackson Hole, population around 20,000-lets test everyone to see who has had it-but do it right by finding the best COVID IgM and IgG antibody test and matching with the COVID RNA nasal pharyngeal swabs to see who is safe to go back to work.  Let’s find a way to protect our other health care workers and patients by knowing their nurse or doctor or respiratory tech or first responder is safe from catching it too.  WE MUST protect our healthcare workers as they are the front line and deserve our thanks and I give them all huge respect.

Complicating matters, not all antibodies are created equal. Some people make neutralizing antibodies that reduce or prevent infection by binding to the virus and make the virus inactive.  One strategy for treatment has been to use blood-plasma transfusions from people who have recovered from past COVID infection appear to help current COVID patients in critical condition.

But it isn’t clear how long these antibodies offer protection. Research from South Korea reported that 91 infected patients tested negative for the virus and then later tested positive again. This could be due to several factors including false-negative test results virus fragments being released even after someone has recovered and the virus is no longer active.

Some early studies from China showed that some patients made no antibodies to COVID while others had a very high antibody response.  In the SARS outbreak in 2002, we found that there was a protection of up to 18-24 months due to the presence of these antibodies.  This week, The World Health Organization said it is unknown which recovered coronavirus patients are immune to a second infection.

I remember in 2002-20003 working the ICU in Phoenix with 90 sick patients with SARS and looking up at the 10-story hospital watching helicopters land wondering if that would be one of my patients that day.  Looking up and seeing the ICU floors as I stepped out of my car for my 36-hour shifts knowing I would be surrounded by SARS patients all day and had 2 young children to come home too.  But we had all the masks/gowns/gloves and other protective gear to change between each patient.  Today, to have to go into that environment not knowing if I had the protective equipment needed would be nerve-wracking. We are seeing that every day in many cities and they still go to work and provide amazing care.  Hospitals and others are using every possible tool to increase protective equipment-even using 3D printers to make surgical masks/protective barrier health care quality masks. Everyone is stepping up to support our teams.  Here in Jackson Hole, we had a local entrepreneur, Colby Cox of Convergence Investments, use his network to find 11,000 masks for our healthcare workers and emergency responders and donated them to our healthcare teams.

Out of chaos comes compassion. Pay it forward, take care of yourself first, then your family then your neighbors and community.  Be smart, stay safe and be passionate about compassion.