As this pandemic plays out, we are learning more and more about this virus.

Currently recommendations about prevention, infection control and treatment, are largely based on how the virus that caused severe acute respiratory syndrome (SARS) were effectively managed.

SARS was caused by the virus called SARS-associated coronavirus (SARS-CoV). This illness, considered the first pandemic of the 21st century circulated in 2003 and affected more than 8000 patients and caused 774 deaths in 26 countries on five continents.

It was deemed contained by 2004 and since then no new cases have been detected.

Based on our current knowledge, COVID -19, caused by the SARS CoV-2 virusappears to be genetically similar to SARS-CoV and infected patients are presenting with a similar clinical illness.

COVID-19 is dissimilar to SARS in terms of its virulence, and therefore our approach needs to be amended.

As I mentioned before, and continue to believe, encouraging widespread testing of non-healthcare associated personnel while in the throes of this COVID-19 pandemic is wrong headed as containment is no longer possible.

Healthcare workers still do not have adequate supplies of Personal Protective Equipment (PPE) so when you go for testing you are amplifying their risk of infection.

Our health should not be put at risk as we do our jobs!

Inevitably, many healthcare workers - my colleagues and friends will unfortunately become infected and die in the course of doing their jobs caring for those suffering. To me this is a high price to pay.

We can lay blame later, but now we need to act, and that action involves you and me and everyone else actively participating to their fullest capacity.

To quote Helen Keller, “Alone we can do so little, together we can do so much!”

Since we cannot leave the hospitals or clinics empty of staff, let us individually agree to protect our health workers.

We have ways to test retrospectively, using two powerful techniques namely – CT chest and ELISA. These will be discussed in other posts.

There was recently an article that stated that some enterprising companies will be marketing home testing kits to test for COVID-19 infections. These kits will set you back $130 plus, but give you peace of mind.

The article mentioned that the test will be using RT-PCR so I would like to take this opportunity to provide you information about RT-PCR and discuss a few reasons why home testing and drive thru testing, although attractive testing options, continue to be ill advised.

In this post I will discuss:

• The reliability of test procedures using RT-PCR and the subsequent results.
• Whether or not the results will change the recommendations previously provided to you.

RT-PCR – Reverse transcription PCR

RT-PCR testing for the COVID19 virus has been deemed highly unreliable clinically and faulty testing has been connected to the under-detection of cases in China and now in the US.

In order for PCR testing to be reliable it must be done under “ideal” conditions”, from tests generation to sample collection and result generation.

Depending on the science used to design the kit, the type and quality of the reagents used in the processing, and the techniques used to collect the sample, these tests can lead to high rates of false negatives a test result that says a condition is absent when it is actually present as well as high rates of false positives a test result that says a condition is present when it is actually absent

High False Negatives

This error results in patients that are potentially infected being deemed “PCR- negative”.

Of course, this creates a false sense of security, and these patients feel emboldened to go out and live life as usual, inadvertently infecting other persons. To combat this scenario, there is strict guidance from the CDC that reads: “ Negative results do not preclude SARS-CoV-2 infection and should not be used as the sole basis for patient management decisions. Negative results must be combined with clinical observations, patient history, and epidemiological information.”

This is the CDC admitting that testing for COVID-19 using, rRT-PCR, is not altogether reliable, but the best we have at this time.

The high rate of false negative results is thought to be occurring because of:
Sampling Problems

• Sample Collection:
• Many discussions about testing state that a nasal or oral swab is needed to test for COVID -19. This is very true but not as simple or straightforward as it seems. Promise!
• CDC recommends: https://www.cdc.gov/coronavirus/2019-ncov/lab/guidelines-clinical-specimens.html
• Collecting and testing an upper respiratory nasopharyngeal swab (NP).
  • Here is how to conduct a useful NP swab. http://www.hss.gov.yk.ca/pdf/npswab.pdf
  • Swab should reach depth equal to distance from nostrils to outer opening of the ear.
• Collection of oropharyngeal swabs (OP) is a lower priority and if collected should be combined in the same tube as the NP.
  • Collection of only OP swab is acceptable if other swabs are not available (as they are less reliable)
    • OP swabs are less reliable as they are largely contaminated with oral bacteria that can lead to irregularities with results.
      • Here is how to conduct a useful OP swab.
      • https://www.health.pa.gov/topics/Documents/HAN/2020-PAHAN-485-03-11-UPD%20-%20COVID19%20I.pdf
• CDC also recommends testing lower respiratory tract specimens, if available.
  • These include inducted sputum, tracheal aspirate, broncheoalveolar lavage (BAL) fluid, pleural fluid.
  • This is ICU work done when you on a ventilator, essentially on death’s door.
• Testing Information Updated 13 Mar 2020

Poor design of some kits
• Because of the pressure to produce as many kits as possible yesterday, the production and standardization of kits are not always reliable.
• Inadequate primers Primers are short strands of DNA made in the lab. They are usually about 20 nucleotides long and can be custom-designed for the purpose at hand. Primer sequences are selected to give the best specificity (targeting of the viral particles for detection, in this case) while allowing for an efficient PCR amplification process. are used – too short or not rigorously specific.
• It has been reported that some kits (even those from the CDC) do not come with the proper reagents a substance or mixture for use in chemical analysis or other reactions needed to run the tests and produce reliable, replicable results.

Timely running of the sample
• Because of the problems with the kits mentioned above, some samples sit and degenerate and are essentially unreliable to test even if “stored” for later reading. (not ideal conditions)
• We do not have enough of the required reagents for sure and likely not enough PCR machines available to meet the demand.
• In addition, not enough of the humans needed to facilitate the process.

High False Positives

High rates of false positives can occur when the environment under which the person being tested has a high bacterial load.

This can be in the hospital:
• Hospitals are places where high numbers of sick people congregate
• Even on a good day, during regular situations, there are high viral loads
• In these times, when everyone with respiratory symptoms want to be evaluated and visit the ER, that viral load is further increased.
• So visiting hospitals or any medical facility open to the public will ensure that you get the infection if you do not already have it.
• Please see my recommendations about what to do if you feel to be tested.

This can occur from being in a home where:
• Multiple persons are ill,
• Especially when the family size is large or where there are young children
• We are still uncertain of the role that kids are playing in infectivity, but findings are suggesting that they are asymptomatic carriers of the infection.
• Hence the school closures.

This can also occur in situations where:
• The person being tested has not been practicing social distancing - recreationally or in work environments.
• Grocery stores
• Restaurants – even those only doing take out
• Pharmacies
• Spring break revelry locations

The test kits that are coming on to the market are not going to provide reliable information or any benefit whatsoever. Remember that these are commercial ventures with an agenda that is not necessarily for your benefit.

There is still not treatment!

There are some promising agents under investigation but nothing that is going to change the course of the disease anytime soon. Please see the treatment article for updates.

Please let us read between the lines with these excerpt from the article referenced above.

“These tests follow the PCR-based method, which tests for the genetic presence of the COVID-19 virus in a patient. These have a high degree of accuracy, at least when performed in a controlled setting and administered by a medical professional, and are the same tests that are available via drive-through testing stations being set up by state agencies.”

In parsing these statements, here is my takeaway:

• RT-PCR is largely unreliable as it results in a high rate of false negative errors and underestimate infection rates. See discussion above.
• The science behind them is not standardized as they have to use different primers to make the tests proprietary. This leads to conflicting interpretations of what is actually positive.
• The high degree of accuracy is derived from doing the testing under ideal conditions.
• You would protest vehemently if I, a professional, do these tests on you, how can I then expect you – a non trained, non medical professional - to do them rigorously on your own, at home?
• See what should be expected when you utilize a home test kit here.
• Here is how to conduct a useful NP swab.
• Here is how to conduct a useful OP swab.
• We have not yet analyzed the results obtained from the drive through testing models for things like benefits and reliability of sampling and reliability of the results obtained.
• They will likely be inferior.
• Inferior tests have a tendency give inferior results.
• Testing for testing sake is not going to quell this pandemic, but will expose more and more persons to infection, including the medical staff doing the testing.

Here is another statement to analyze, again from that article:

“ At-home use is relatively new to market, and could introduce some potential for error in the collection part of the process, but both Carbon Health and Nurx are offering consultation with medical professionals to help ensure that samples are collected properly, and that results, when available, are correctly interpreted and provided with guidance on next steps for those taking the tests”

So again in parsing this:

• Why is there the proliferation of a test method whose results are admittedly going to be systematically and repeatedly compromised by the erroneous collection of the sample?
• Let me see, …inferior testing method + equivocal science behind the fundamentals of said tests + inferior sample collection ……= Viola! Accurate, reliable test results!
• Really? I don’t think so!
• They are going to provide medical professionals to provide guidance on next steps to take after testing, where available.
• As I mentioned before,
• There is still not treatment!
• The same things that were being asked of you before testing is going to be asked of you afterwards. So……

The only thing that will be reliably being collected with these home tests is your DNA sample.

Save your money and protect your privacy. In retrospect, eventually everyone will be assessed.

Read the following to understand what is occurring in the DNA collection industry these days.

https://www.nytimes.com/2018/03/14/health/theranos-elizabeth-holmes-fraud.html
https://www.cnbc.com/2020/01/23/23andme-lays-off-100-people-ceo-anne-wojcicki-explains-why.html
https://www.cnbc.com/2020/02/05/ancestry-layoffs-of-6percent-100-people-amid-dna-test-slowdown.html

If you think you are infected please follow the CDC guidelines here.

Please follow the recommendations provided here.

Additional Resources:

https://knowledge.pcrdrive.com/wiki/Types_of_PCR_Primers
http://www.premierbiosoft.com/tech_notes/PCR_Primer_Design.html
https://www.khanacademy.org/science/biology/biotech-dna-technology/dna-sequencing-pcr-electrophoresis/a/polymerase-chain-reaction-pcr