Originally Published May 5th, Updated June 12th

This summary is intended to be utilized as a source of information regarding the different types of COVID-19 tests available, their benefits and drawbacks, as well as their potential uses in the workplace. Information changes rapidly in this space, and as such, the information provided below is accurate as of the day of publication. Our understanding of the virus, the disease, recovery, immunity and testing applications has and will continue to evolve. We will aim to update this when new information becomes available.

ABOUT SARS-CoV-2

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a virus which is part of the coronavirus family. The virus is what causes COVID-19 (COronaVIrus Disease 2019), which is the name for the illness caused by the virus. There are many examples of types of coronavirus, with disease severity ranging from mild (the common cold for example) to severe (Severe Acute Respiratory Syndrome or SARS CoV and Middle East Respiratory Syndrome or MERS CoV).

For simplicity sake, for the remainder of this article, “COVID-19” will be used when referring to both the virus and the disease it causes.

There are many differences between COVID-19 and SARS or MERS, namely the extremely high transmissibility of this virus (meaning how easily it can spread from person to person). This new virus, which was first detected in December 2019 in China, has had tremendous spread throughout the world with 188 countries impacted, over 7.3 million confirmed cases and over 400,000 deaths[1] in just over 5 months.

The figure below is accurate as of June 11, 2020[2] illustrating how the virus has impacted Canadians to date.

INTRODUCTION

The COVID-19 pandemic has had a tremendous impact on every aspect of our lives. Canadian workplaces are looking for safe and effective ways to manage this in their workplace, to return to previous working conditions, and/or to better understand how to manage cases that may occur. All of these, however, require a deeper understanding of the disease itself, how our body responds to the infection and the options currently available in Canada for testing of employees.

The chart below summarizes the current availability of tests for COVID-19 in Canada.

*TAT = turnaround time

**PCR = reverse transcription–polymerase chain reaction (RT-PCR, or just ‘PCR’)

***Health Canada has changed the authorization to that of research use only as of May 2, 2020

EXECUTIVE SUMMARY

There are four main types of tests for COVID-19. Three tests attempt to diagnose the virus (PCR testing and CRISPR technology tests for fragments of the genetic material and antigen testing which detects the presence of proteins of the virus). The last type of test detects antibodies produced by our body when we have been exposed to the virus. This test on its own is not an effective diagnose the disease.

At the moment, the only available and accurate test to diagnose the disease is PCR testing, either in the laboratory or by a point-of-care (POC) device. There is the availability of lab-based PCR testing for workplaces in Canada, but challenges still remain, including lab capacity in some provinces. Currently, some provinces have permitted private lab samples to be tested.

CRISPR technology is a newer genetic test that can easily and quickly detect the presence of small quantities of viral genetic material. To date, there is one test lab-based CRISPR test that has U.S FDA Emergency Use Authorization (EUA) but none that are Health Canada authorized or pending review. There are many companies working to produce POC CRISPR tests that are inexpensive and accurate for diagnosis with a fast turnaround time. Some of these are looking at using saliva instead of nasal swabs. As more information becomes available, a deeper discussion of this technology will be added to this paper.

Antigen testing may have a future role in mass screening for the virus. At the time of print, there is one antigen test that has U.S FDA EUA but none that are Health Canada authorized or pending review. Antigen testing would allow for mass screening, with a fast turn-around in the workplace. Once there is the availability of Health Canada Authorized devices for antigen testing, the sensitivity, specificity and accuracy would still need to be reviewed prior to recommendation for use in the workplace. These would be considered screening tests only and will need to have additional testing to confirm a potential diagnosis.

Serological testing can be completed in the laboratory or as POC tests. Even with highly accurate tests, there are many unknowns, including interpretation of the results. Although some preliminary evidence exists showing that the presence of antibodies are likely protective (neutralizing) and will provide immunity, we do not have evidence to fully understand how robust the immunity is, or how long it lasts.. More studies are needed in order to understand the virus, our bodies reaction to this and whether or not antibodies will indeed protect us from future infection.

To better understand how these tests may be able to be utilized in the workplace, please see the detailed explanations below.

COVID-19 FACTS

To date, there is a growing range of information that we know about this virus and yet, there are many questions that still remain unanswered.

The following is a brief summary of information that we currently believe to be true regarding COVID-19 infections:

The virus spreads through respiratory droplets (from coughing, sneezing, speaking, spitting)
These droplets may travel 2 meters to infect others
An individual may shed the virus (and can therefore spread it to others) for days prior to having any symptoms (pre-symptomatic)

o Individuals can spread the virus 2 - 4 days before symptom onset (with a peak infectiousness occurring at 0.7 days before symptoms begin)[3] [4]

o It is estimated that pre-symptomatic transmission accounts for 44% of secondary cases[5]

Some individuals (children for example) may remain asymptomatic and spread the virus, never realizing that they are infected or are transmitting the virus to others. How much this contributes to community spread however is uncertain.
The virus can live on surfaces for variable periods of time (depending on the surface). An individual can get infected if they touch a surface contaminated with viral particles and then touch their mouth, nose, or eyes before washing or sanitizing their hands.
The virus can easily be killed on surfaces by using common cleaning agents (bleach, alcohol-based cleansers, disinfectants). See https://www.canada.ca/en/health-canada/services/drugs-health-products/disinfectants/covid-19/list.html for more specific information if needed

Preventing infection can be accomplished by:

o Frequent hand washing using soap and water for at least 20 seconds

o Use of alcohol-based hand sanitizers containing at least 60% alcohol

o Avoidance of touching your face including mouth, nose or eyes

o Maintaining a physical distance of 2 meters or more from all other individuals

o Wearing personal protective equipment (PPE)

PCR TESTING

Real time PCR detects fragments of RNA (genetic material) from individuals infected with the virus. The test generally requires the use of a swab (nasopharyngeal swab, mid-turbinate, anterior nares or oropharyngeal for most of the tests with the potential for saliva testing being investigated currently). The results can take hours to days when tested in the laboratory.

There are many companies who have developed tests conducted by real time PCR and many do have Health Canada Approval. See the list of authorized devices for diagnostic testing of COVID-19 at https://www.canada.ca/en/health-canada/services/drugs-health-products/medical-devices/covid-19/diagnostic-devices-authorized.html

Health Canada authorization is required if considering use or purchase of a diagnostic device:

“Only diagnostic tests authorized by Health Canada can be imported or sold in Canada. Unauthorized tests may not produce accurate results, leading to potential misdiagnosis. Health Canada has confirmed that authorized COVID-19 tests are well supported by evidence indicating they will provide accurate and reliable results.”

As of June 11, 2020, Health Canada has approved lab-based PCR tests (meaning that they must be used in a laboratory setting) and two point-of-care tests (POC test which can be used outside of a laboratory), one of which is now only approved for research purposes (Spartan). There are however many other diagnostic tests that have applications currently being reviewed; there is only one POC PCR test under review at the time of print (https://www.canada.ca/en/health-canada/services/drugs-health-products/medical-devices/covid-19/diagnostic-devices-applications.html#wb-auto-5).

A positive PCR tests occurs when there is the presence of fragments of the genetic material of the virus (whether alive or dead). In individuals with symptoms (including fever, chills, cough, upper respiratory symptoms, GI symptoms, body aches etc.), who test positive, a diagnosis of COVID-19 can be accurately made.

In asymptomatic individuals, a positive result may be due to one of the following:

The presence of the virus in the few days prior to symptom onset – pre-symptomatic
The presence of the virus in an individual who is asymptomatic and will not develop symptoms (or minimal symptoms not thought to be from COVID-19)
The persistence of viral fragments after recovery from COVID-19 (occurring from either live fragments or dead fragments which are still clearing the body). The individual may or may not be contagious. More information regarding this is needed.

There are individuals with the illness who may test negative on a PCR test. This may occur for many reasons as the accuracy of these types of tests can be impacted by:

Sample type (throat, nasopharyngeal, lower respiratory tract samples) – depending on the stage of the disease, the virus can be found more easily in different samples. At the early stages of infection, the virus tends to be found predominantly in the upper respiratory tract. After time, it migrates to the lower tract where it is easier to detect the virus with throat swab or lower respiratory samples.

Skill of sample collection – it is important to ensure that samples are adequate and completed in a way that ensures the highest rate of detection
Stage of the infection (too early to detect enough fragments of the RNA for example)
PCR assay being used (this can vary from test to test)

APPLICATION FOR PCR TESTING IN THE WORKPLACE

In general, PCR tests remain the only available and best way to diagnose COVID-19 currently. Both laboratory tests as well as many POC tests offer effective, sensitive, specific and accurate tests, however as of the date of writing, laboratory testing offers many advantages.

Laboratory testing at a Canadian lab is available in some provinces. There is the ability to send tests to the U.S. for testing as well, however this can be more costly with a slightly longer turn-around-time, and some provinces require a Ministry-approved lab (a requirement that U.S. labs would not meet). The turnaround time for lab testing completed in a Canadian lab is typically next day, if the sample arrives at the lab same day or next morning.

Although POC PCR tests will have the ability to have results available at the site within hours, at the moment, they are limited due to the following:

Availability of the devices
Only one Health Canada authorized device that is currently available for use in Canada (Spartan is also Health Canada approved but only for research purposes at the time of print)
Limited quantity of tests that can be performed at once

DriverCheck has been at the forefront of investigation into available PCR tests. As the availability of Health Canada authorized POC devices expand in Canada (which is expected to occur by July 2020), DriverCheck will be able to provide you with a detail of the specific benefits and drawbacks of each option. DriverCheck has the capability to coordinate lab-based PCR testing, but challenges still remain, including lab capacity. Currently, lab samples are being tested privately in some provincial labs and US labs. We do expect lab capacity in Canada to continue to increase.

SEROLOGICAL TESTING

The following is a brief summary of information that we currently believe to be true regarding recovery and antibody protection:

For many individuals who have been exposed to the virus, there are production of antibodies

o IgM, IgG and IgA are some of the antibodies that are produced after COVID-19 infection

o There are some individuals however that do not appear to produce these antibodies after infection (or the levels are below that which can be detected)[6]

o The term “neutralizing antibody” refers to antibodies that can protect you from future infection

§ Neutralizing antibodies bind to a virus in a manner that blocks infection

§ Only a small subset of antibodies that bind to a virus are capable of neutralization

§ It may take a long period of time to produce these neutralizing antibodies

o Approximately 30% of patients who have recovered from COVID-19 had very low levels of neutralizing antibodies[7]

o There is reason to believe that presence of antibodies do indeed provide at least short term protection against reinfection; however, more research is needed to confirm this

o We do not have long term data to follow the levels of any antibodies produced (meaning that we do not know how long the antibodies will remain in our body)

o We do believe that those who had a more severe clinical classification of COVID-19 produce higher levels (or titers) of antibodies

o It can take approximately 2 weeks or more for individuals to produce some of the antibodies

o Antibodies can be present at the same time as the virus RNA can be detected

§ Meaning that an individual MAY continue to be contagious even with the presence of antibodies

APPLICATION FOR SERIOLOGICAL TESTING IN THE WORKPLACE

The idea of “immunity certificates” has been gaining more and more interest across the world, with news articles showing up daily touting this to be the best way for countries to return to “normal life”, including returning individuals to work. However, there are many limitations and unknowns that must be considered.

Serological tests identify the presence of antibodies that are produced by our body in response to COVID-19. As with PCR testing, there is the ability for laboratories to test for the presence of antibodies as well as POC serological tests.

At the moment, there are four Health Canada authorized tests to be used in the laboratory for antibody testing only. There are other lab-based antibody tests that are under review by Health Canada (https://www.canada.ca/en/health-canada/services/drugs-health-products/medical-devices/covid-19/diagnostic-devices-applications.html).

There are no Health Canada approved POC devices for serological testing, however there are many that are currently under review (https://www.canada.ca/en/health-canada/services/drugs-health-products/medical-devices/covid-19/diagnostic-devices-applications.html#wb-auto-5).

Currently, there are a considerable number of issues with POC serological testing, such as quality and interpretation of the presence of antibodies, that need to be addressed before widespread use in the workplace can be considered. Tests vary in sensitivity, specificity and accuracy.

Even in those devices which appear to have high sensitivity and specificity (exceeding 97%), false-positive rates can exceed the true positive rates in a population with low % of actual positives. In other words, if the rate of infections in Canada (or previous infections) is only 1%, but the false-positive rate is 3%, then the test will have significantly more false-positive results than true positives. As the prevalence of the disease increases, the percentage of positive that are false will decrease.

The implications of false-positives with serological testing are numerous in comparison to PCR. When an individual has a positive diagnostic test (PCR) for the virus, they will require self-isolation. They will either develop symptoms or not. In the case of a false positive PCR test, so long as they are asymptomatic for at least 24 hours with a minimum of 10 days since symptoms began, they can return to work. However, in an individual with a false positive serological test, there may be a false sense of security putting the individual at higher risk of infection (given the lack of antibodies that may protect them). Individuals who believe that they have antibodies may then be less likely to follow the strict physical distancing and precautions necessary to avoid disease. They would then be at an even greater risk of infection. Additionally, as mentioned above, there are limitations in our knowledge of how to interpret a positive serological test and what this will actually mean for individuals.

At this time, even with a true positive test for antibodies, we cannot confirm the following:

The length of time the antibodies will continue to be detected
Whether or not the presence of antibodies definitively means that the individual is protected from re-infection
If they are indeed protected from re-infection, how long will this last?
Whether or not the individual also has the presence of the virus and would be able to spread this to others (meaning that the antibodies are starting to be produced while the virus is still present)

Based on the above, serological testing cannot be used in isolation to diagnose COVID-19 nor at this time, does it appear that it can accurately be relied upon and used as an “immunity certificate”. There is reason to believe however that as our knowledge increases and accuracy of these tests improve, we may be able to utilize these tests to help diagnose (when used in combination with PCR testing, CRISPR technology and possibly antigen testing) and increase our knowledge of population occurrence rates.

Despite the available Health Canada authorized lab based antibody tests, the implications for the workplace are still limited due to a lack of studies to be able to provide accurate interpretation. Once there is more data available, our ability to use these tests in the workplace will increase. The combination of PCR testing and serological testing (so long as the test is highly sensitive) has some merit[8]. Using the results of both, we may be better able to interpret results of a positive or negative PCR test.

ANTIGEN TESTING

Antigen testing is not a new type of test. This process is used for rapid testing for other illness such as strep throat and the flu (“rapid strep test” and “rapid influenza test”). An antigen test is a screening test and will detect proteins from the virus causing COVID-19. At the moment, these are not available in Canada and the World Health Organization has recommended against the use of this type of test until accuracy increases and more research is conducted:

“At present, based on current evidence, WHO recommends the use of these new point-of-care immunodiagnostic tests only in research settings. They should not be used in any other setting, including for clinical decision-making, until evidence supporting use for specific indications is available.[9]”

Once approved by Health Canada, an antigen test can be completed on-site, is rapid (results occurring within minutes) and therefore would work well for large scale screening. At the moment there are issues with accuracy, and it appears that false negative tests are more common than false positive results.

False negative results however can occur in 20 – 70% of tests. This is due to a number of reasons including:

Low levels of proteins from the virus. The test requires large quantities of the virus and therefore may not detect individuals at the onset of symptoms.
The accuracy is dependent on the sample taken. Once again, if the sample does not include a large quantity of viral proteins, the test may be falsely negative.
The proteins are only detected with active replication of the virus and therefore may only be able to detect the virus during early infection.

False positive results can occur if the test recognizes similar proteins from other similar viruses and therefore is very dependent on the device itself.

It is important to note that, in general, a good screening test is one that is highly sensitive (that will not miss any potential disease). It is very important that the rate of false negatives be extremely low before these types of tests can be effectively used as large scale, on-site screening tests. False negative tests have great implications and may end up with an individual falsely believing they are not shedding the virus and still be contagious to others. In a workplace setting, this could mean quick spread of the virus across the workplace.

APPLICATION FOR ANTIGEN TESTING IN THE WORKPLACE

An antigen test can be completed on-site, is rapid (results occurring within minutes), is cost-effective and therefore would work well for large scale screening.

There is potential to be able to utilize this type of testing if and when available. DriverCheck will continue to stay on top of the potential availability for antigen testing options, and will be able to provide you with a detail of the specific benefits and drawbacks of each option.

SUMMARY OF TESTING IMPLICATIONS FOR THE WORKPLACE

In a perfect world, workplaces should have the ability to ensure that workers are not presenting to work during the pre-symptomatic phase (the few days prior to presenting with symptoms of COVID-19) or being completely asymptomatic but shedding and spreading the virus. As well, for employees presenting with some minor symptoms that may be consistent with COVID-19 (nasal congestion, sneezing for example), having the ability to rule-out COVID-19 infection would be ideal. This can be accomplished by testing individuals using PCR to detect the presence of the virus. Although with current testing it appears that some individuals may test negative and yet be able to spread infection, with proper techniques of swabbing, and accurate technology, the risk of this appears to be decreased. If there is the ability to complete serological testing as well as PCR testing, false negative rates appear to be reduced. When combining the two tests, the accuracy of diagnosis can increase substantially[10] and the interpretation for individuals may also be better understood.

DriverCheck has the capability to coordinate private lab-based PCR testing, but challenges still remain, including lab capacity. Currently, lab samples would be referred out to a US lab for analysis as all lab capacity in Canada is dedicated to Public Health. We do expect there to be lab capacity in Canada soon though, as early as June.

At the moment there continues to be uncertainty of protection against future infection in individuals who have recovered and have antibodies against COVID-19. This, as well as the concerns regarding the risks of false-positives as explained above, are the main drawbacks of using serological testing on its own.

With a daily growth in serologic testing technology and an increasing knowledge of the interpretation of the presence of antibodies (and their ability to protect from future infection), it is expected that there will be a future role of serological testing for the workplace. At this time, even with accurate testing, the interpretation of the presence of antibodies remains unclear.

Antigen testing may become an effective screening tool for workplaces in Canada. This however very much depends on the ability to develop these tests with high sensitivity (very low false negative rates). If this occurs, antigen testing will provide workplaces with a quick, on-site test that can easily screen large numbers of individuals. It is important to note that these will be considered screening tests and verification by other methods may be needed.

DriverCheck’s goal is to be at the forefront of testing for COVID-19. We offer our clients the most up to date information, as well as ability to use testing to safely operate your business during this pandemic (where possible and allowed by federal and provincial governments). We will continue our pursuit of the best approach for both diagnosis, as well as protection of the spread of COVID-19 in your workplace.

1 COVID-19 Dashboard by the Centre for Systems Science and Engineering (CSSE) at Johns Hopkins University, May 4, 2020

2 https://www.canada.ca/en/public-health/services/diseases/coronavirus-disease-covid-19.html?utm_campaign=not-applicable&utm_medium=vanity-url&utm_source=canada-ca_coronavirus

3 He, X., Lau, E.H.Y., Wu, P. et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. Nat Med (2020). https://doi.org/10.1038/s41591-020-0869-5

4 Arons MM, Hatfield KM, Reddy SC, et al. Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facility. N Engl J Med. DOI: 10.1056/NEJMoa2008457.

5 He, X., Lau, E.H.Y., Wu, P. et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. Nat Med (2020). https://doi.org/10.1038/s41591-020-0869-5

6 Fan Wu, Aojie Wang, Mei Liu, Qimin Wang, Jun Chen, Shuai Xia, Yun Ling, YulingZhang, Jingna Xun, Lu Lu, Shibo Jiang, Hongzhou Lu, Yumei Wen, Jinghe Huang. Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications: medRxiv 2020.03.30.20047365; https://doi.org/10.1101/2020.03.30.20047365

7 Fan Wu, Aojie Wang, Mei Liu, Qimin Wang, Jun Chen, Shuai Xia, Yun Ling, YulingZhang, Jingna Xun, Lu Lu, Shibo Jiang, Hongzhou Lu, Yumei Wen, Jinghe Huang. Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications: medRxiv 2020.03.30.20047365; https://doi.org/10.1101/2020.03.30.20047365

8 Juanjuan Zhao, Quan Yuan, Haiyan Wang, Wei Liu, Xuejiao Liao, Yingying Su, Xin Wang, Jing Yuan, Tingdong Li, Jinxiu Li, Shen Qian, Congming Hong, Fuxiang Wang, Yingxia Liu, Zhaoqin Wang, Qing He, Zhiyong Li, Bin He, Tianying Zhang, Yang Fu, Shengxiang Ge, Lei Liu, Jun Zhang, Ningshao Xia, Zheng Zhang, Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019, Clinical Infectious Diseases, , ciaa344, https://doi.org/10.1093/cid/ciaa344

9 World Health Organization https://www.who.int/news-room/commentaries/detail/advice-on-the-use-of-point-of-care-immunodiagnostic-tests-for-covid-19

10 Juanjuan Zhao, Quan Yuan, Haiyan Wang, Wei Liu, Xuejiao Liao, Yingying Su, Xin Wang, Jing Yuan, Tingdong Li, Jinxiu Li, Shen Qian, Congming Hong, Fuxiang Wang, Yingxia Liu, Zhaoqin Wang, Qing He, Zhiyong Li, Bin He, Tianying Zhang, Yang Fu, Shengxiang Ge, Lei Liu, Jun Zhang, Ningshao Xia, Zheng Zhang, Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019, Clinical Infectious Diseases, , ciaa344, https://doi.org/10.1093/cid/ciaa344

Dr. Melissa Snider-Adler, M.D., C.C.F.P.(AM), M.R.O. (AAMRO), D,A.B.A.M.

Chief Medical Review Officer, DriverCheck Inc.

Physician, Addiction Medicine

Dr. Snider-Adler is the Chief Medical Review Officer for DriverCheck and is a Board-Certified Addiction Medicine Physician with a Certificate of Added Competence in Addiction Medicine.

Dr. Snider-Adler currently practices addiction medicine in Oshawa, Ontario and is an Assistant Professor at Queen's University Department of Family Medicine. She works as a Peer Assessor for the College of Physicians and Surgeons of Ontario.

Dr. Snider-Adler is considered an expert in the field of substance use in the workplace as well alcohol and drug testing for safety sensitive workplaces. As such, she is often asked to provide expert opinions, reports and testimony for arbitrations, hearings and court cases across Canada.

Dr. Snider-Adler travels across Canada and the U.S. speaking to workplaces and at various conferences regarding the impact of recreational cannabis, cannabis for medical purposes, workplace substance use, and addiction prevention and treatment.

Using COVID-19 Testing in the Workplace