In the April issue of HIMCC, I contributed an article on Deep Space Medicine. My essay raised the potential of new diagnostic laboratory testing that would be required for people to live in deep space near the moon or Mars, while having practical applications on earth in parallel to space. While researching the deep space medicine article, I corresponded with several experienced specialists in the clinical laboratory field, Kris Bailey and Bonnie Reib.
Kris Bailey, President of AiCon Inc., and I originally worked together on the transformation and automation of the MDS Ontario laboratory beginning in 1993. Over the next decade, she and I worked together on several significant laboratory projects including the Ontario Regional Laboratory Strategy Project (ORLSP) and the BC Provincial Health Services Authority Laboratory Integration Strategy Project. Bonnie Reib and I first worked together in mid-1990’s to transform laboratory services for the new regional Capital Health Authority in Edmonton. Later, Bonnie and I were both employed by Sick Kids Hospital; myself as Director of Applications and Bonnie as the Managing Director for the Department of Paediatric Laboratory Medicine.
In early 2000, Kris and Bonnie each raised caution flags that disruptive changes from the current established diagnostic laboratory testing infrastructure in Canada could take years to evolve. Sometime in the future, we would have quality, near patient diagnostic testing accessible in every urban/rural/remote community hosted by a neighborhood pharmacy, with test results automatically uploaded into electronic health records, forwarded to a patient via text message or email or personal health record refresh. For public health testing, it is most important that all positive test results are uploaded in real time into the jurisdiction’s communicable disease and outbreak management solution to enable community tracking and case management. Twenty years later, these disruptive changes have not been implemented in a cohesive manner.
Fast forward a few years, we are witness to the emergence of the global pandemic of COVID-19 virus. Last Friday, two significant events, one in Canada and one in the US. Prime Minister Trudeau announced formation of COVID-19 Canadian immunity expert panel to be led by Dr. David Naylor. Later the same day, the US President led a press conference on the White House lawn to announce the immediate expansion of community laboratory testing for COVID-19. The announcements included participation by each of the major pharmacy chains across all of the US, and support for both molecular diagnostic identification and serum antibody testing. Currently, intravenous specimen testing is deemed necessary to achieve the desired accuracy, such as Roche’s Immunochemistry analyzer with 100% accuracy for detecting COVID-19 antibodies and 99.8% accurate for ruling them out. The pandemic has dictated our priorities that earth-based application will arrive before deep space application.
Kris has authored the following timely and informative essay on “Lab Testing for CoronaVirus – Reality, Log Jams and So What?”
Lab Testing for Coronavirus – Reality, Logjams and So What?
Lab testing serves three useful purposes, diagnosis, monitoring and surveillance. As I listen to the political representatives, I am perplexed at the lack of understanding of what lab testing is and its contribution to disease management and public health surveillance. I will attempt to explain what, why and so what?
There are 2 tests:
Test for the virus – this is done in a lab looking for the COVID messenger RNA strand to determine if the patient has the virus. The patient’s cells are captured using a swab up the nose and put into a medium to protect the cells prior to testing.
Test for antibodies – this is done using serum or plasma for the detection of IgM and IgG antibodies against the SARS-CoV-2, also called serology.
Tests are created; they do not sit on a shelf waiting to happen:
As of 21 March 2020, the US CDC recommended RT-PCR test method is to be used to detect and confirm the presence of the coronavirus’ RNA in very recent or active infections. It is a very specific and reliable test. IF there are living cells and the test is positive, there is certainty. The diagnostic companies that product this test are Abbott, DiaSorin and Roche (there are other companies as well). Rapid tests (also known as point of care) for this virus are available from Cepeid (which has been performing influenza testing for a few years) and Spartan Cube (new to the market). Other companies are entering this market quickly.
Detection of antibodies can be used both for diagnosis and population surveillance. The antibody tests are not yet fully developed, nor is it how certain patient immunity is. Rapid tests are quicker to manufacture and easy to use but have to be carefully designed and validated. Quality control and validation take time and money along with larger population studies than the PCR virus test. Inaccurate tests could be devastating. If the serology test is incorrectly determined to show immunity, non-immune people would go to work, and if they are carriers or pre-symptomatic, they could infect others and the virus would spread. It is important to note that many of these tests have accuracy rate around 80%. The rate of error varies with the disease. For some infections, tests can give you a positive result, if you’ve not had the coronavirus, but you may have antibodies against something similar that could also produce a positive result.
All tests once created, tested and validated, must be approved for use by the FDA in the US or Health Canada in Canadian jurisdiction. At this point, the organization that make the test must create the product and the distribution channel for issuance.
Tests don’t magically appear. When a new virus or bacteria emerges, it must be studied molecularly and microscopically to determine if this is something brand new, a mutated strain of something we already have seen or know about or something that is old and re-emerging (like TB). And then the real work begins where the scientists and disease control organizations constantly work on the old and the new.
What can go wrong here? The virus or the bacterium is unstable, is low in number and is not viable (meaning doesn’t live long). All this to say, it can take a long time to isolate and create a robust test to identify this in a human. Once done, there may not be enough studies and test environments to ascertain its viability and efficacy. Rushing this process to market is very dangerous. Negative test results do NOT confirm that a person doesn’t have the virus …. It just hasn’t reached a level to create a positive result.
Lab samples are collected.
A collection kit requires a swab, test medium and a requisition to identify the patient and their demographic particulars. Collection is tricky, so people who are trained and protected with PPE are required. The container needs to be correctly labeled with the patient particulars.
What can go wrong here? Insufficient swabs and collection kits (including transport medium), not having appropriately trained people to collect and label, and/or no PPE for collection staff.
Samples are transported to a lab for testing.
Samples are packaged up at the collection areas (drive through spots, identified collection depots, hospitals). Sample packages are picked up by a courier and then taken to identified labs for testing or for further shipment (air, train, bus, mail, courier).
What can go wrong here? Too few labs with enough testing capacity, log jammed logistics, sample packages not prepared properly and/or sent to the wrong designation or lost.
Testing Lab receives and tests samples.
Once the sample is received at a lab, each sample package is inspected to ensure requisition, swab and medium is safe for opening. The information from the patient is entered into a laboratory information system and the sample is then tested. Competent medical laboratory technologists manage the assay (test) along with standards and quality control material. Once the assay has completed its testing protocols, the results are made available to the technologist who reviews the quality control, standards, analyzer performance and the patient results. Assuming everything meets qualified standards and limits of error, the results are released from the analyzer to the laboratory information system. POSITIVE results are called by the lab staff to the Public Health Unit.
What can go wrong here? A scarcity of cells were collected with inconclusive results, inadequate supply of trained people to operate the volume of work, too few analyzers (equipment) with operating capacity to perform the volume of work, not enough testing reagents, no PPE for laboratory staff, too few lab testing sites made available for testing (this is normally assessed by the Ministry of Health in conjunction with Public Health).
Public Health, ordering physicians or others receive test results to take action.
This is tricky. Most labs, if not all, send lab results electronically to the ordering clinician.
What can go wrong here? If there is no electronic connection between the lab and the ordering clinician or public health, there is a requirement to fax, phone, or mail results that takes time.
If specimens are collected, via point of care, there is not the same rigour and protocols to collect patient information, test results and distribute the results to those that need it (public health and clinicians). This is the biggest logistical barrier to receiving laboratory results as very few to no labs are electronically connected to public health or to national registries.
The contribution of laboratory testing to Diagnosis, Treatment, Monitoring and Surveillance
Diagnostics is a critical and important part of disease management. The patient care or clinical skill required to identify the problem and the care needed is also important. Identifying the COVID-19 virus includes patient presentation, temperature taking, chest Xray, oxygenation level and a positive Covid RT-PCR test.
To quantify the spread, tracking of a patient’s interactions is required (also called contact tracing). This can be achieved in real time using telecommunications and “tracking apps” on cell phones; otherwise this is a significantly manual and slow process requiring the patient to recall whereabouts and interactions for up to 14 days.
To treat a positive COVID-19 patient requires isolation, oxygen, drugs and treatment protocols.
To determine if a patient has immunity, a blood test is performed for IGG and IGM antibodies. It is not yet proven that serology will be helpful. Many, but not all communicable diseases, have vaccines (COVID-19 vaccine does not exist today in manufactured form). This virus will remain communicable for several more months while the general population goes back to something akin to “normal”.
To keep people safe, social distancing, handwashing, wearing masks, taking temperatures and staying home when sick, helps reduce the spread. To understand the broader disease progression requires national disease registries.
Can wide-spread lab testing be attained and tracked?
To determine if a patient is sick, testing for the virus matters and is the cornerstone of identification and surveillance. Coronavirus is a family of single-stranded RNA viruses that include the causative agents of MERS, SARS, and COVID-19. Coronaviruses causes one-third of common colds. The questions to answer scientifically, clinically, and compassionately should be:
- Should everybody be tested?
- Do we have “specific” serology tests for this family of viruses?
- Do we have a vaccine for the common cold?
- Do we have a vaccine for MERS or SAR
- Will more viruses arise in the future?
- Can other mechanisms be quickly and effectively introduced into normal living?
Why can’t we get thousands of tests up and running? As imperfect as our health systems are, lab testing does matter and does impact a patient’s treatment, such as the PCR test for the virus. Clinical observation and simple tests also matter to determine what is wrong and how sick a patient is. Public Health registries of communicable diseases and contact tracing are important to prevent illnesses from being spread in a family or community as they can lead to serious illness and even death.
My supposition is, change the way we as humans interact, learn to wash our hands frequently, keep surfaces clean, wear masks where appropriate, don’t go to work or out in public when sick and use diagnostic testing that impacts outcomes. How hard can that be?
Other longer-term thought needs to be given to congregate living, including many inputs.
Laboratory testing is the cornerstone of virologic and bacteriologic pandemics; they must be made available broadly coupled with contact tracing and national registries of positive tests.