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Allan Maynard – May 8th, 2020

There is a great deal of new information along with political noise about testing for the CoVid 19. For the past 6 weeks, almost all countries have been in various forms of lock-down; in some cases a complete shut down. Understandably there is desire by most citizens to be able to safely move past this phase and return to some sense of normality, however that may be defined for our post CoVid future. Most medical experts caution though, that the key to slowly re-opening our economies is to significantly ramp up testing, followed by quarantining those who test positive and additionally tracing and testing their contacts.

For most countries, the testing frequency is insufficient despite the statements of some politicians. Some examples – testing totals per 1000 citizens as of May 3rd, 2020 – Italy -34, Germany – 30, USA – 20, Canada – 22, South Korea – 12, France – 11. The South Korea numbers may seem low in comparison but that country was very quick to implement widespread testing, combined with combined with contact tracing and isolation which enabled the country to ‘flatten the curve’ (slow infection rates) much earlier than other countries. The USA had a slow start due to a defective test system but is now catching up. The UK also had a late start. Both countries have unfortunately, been following an infection trajectory comparable to Italy.

According to most medical experts, even though testing numbers increased through April, the numbers are still insufficient to allow a substantial opening of commerce. For instance – the USA has now conducted just over 6 million tests in total but the target should really closer to 1 million per day (about 10 times more than over the past 2.5 months). France is now conducting 700,000 tests per week. In the UK the target is 100,000 tests per day. Canada has set a goal of over 500,000 tests per week. It should be noted however that increased testing will not have the desired outcome unless it is accompanied by contact tracing and isolation. Moreover, herd immunity, an epidemiological concept that describes the state where a population is sufficiently immune, will not be possible until a vaccine is available – likely 1.5 years away at the earliest.

To meet the ever-increasing demand for more testing, research has expanded around the globe to produce more, better and faster tests. The latest count – there are over 60 forms of the viral swab PCR tests and over 130 forms of the antibody tests. Many of these have been introduced without undergoing full approval processes in the various countries. In the USA – the FDA provides an “Emergency Use Application (EMA)” for many of the new tests. This can be sensible in such dire situations as long as the tests’ performance characteristics are very carefully monitored.
So – how are the various tests performing?

THE PCR TEST FOR THE COVID 19 VIRUS – MAIN ISSUE – FALSE NEGATIVES. – As described in my earlier blog, the first type of test introduced worldwide, the polymerase chain reaction (PCR) test, diagnoses CoVid infections by analyzing virus material in mucous collected from the nose and/or back of the throat. The test then isolates the genetic components of the virus and converts it into DNA (Deoxyribonucleic acid). Then, using “polymerase enzymes”, the DNA is duplicated again and again so that there’s enough to be detected (if it is present at all). This process is known as “amplification.”

The inherent issue with this test is that the incidence of false negatives can be high. This makes sense. If a patient is tested too early in the disease, there may not be a sufficient viral load to be detectable. If a patient is tested later in the disease, the viral material is likely concentrated more in the lungs and trachea and thus may not be isolated.
Furthermore, there are now a number of more rapid PRC tests on the market without the same degree of amplification of the DNA. This may mean there is less genetic material within the test, for detection. There are now a number of studies underway or reported that show the incidence of false positives can be significant. In the early stages of the pandemic, Chinese scientists published a paper that found the false negative rate of some of the tests conducted at the Third People’s Hospital in Shenzhen, southern China, between Jan. 11 and Feb. 3, were as high as 40 percent.

More recent studies (University of Cleveland, Mayo Clinic) calculate a false positive rate of closer to 15% and stress the need for follow-up tests to reduce the health risk created by infected people mistakenly being told they are infection-free. This objective of repeated testing is hampered by the shortage of supplies needed to conduct the PCR tests. Many who should be re-tested or even initially tested, are not able to do so.

These problems may seem untenable but that is not the case. The PCR test is highly complex. The global developments to expand testing and speed up test results are impressive. The main point, the limitations of the test must be well understood and further assessed as we deal with the CoVid health crisis.

ANTIBODY TESTING – MAIN ISSUE IS FALSE POSITIVES – The second kind of test involves testing blood samples for the presence of antibodies to the virus. Antibodies are evidence of the body’s reaction to an infection. The presence of CoVid antibodies might then suggest that the person is now immune to the virus. It should be cautioned however, that the notion of immunity to the CoVid virus being acquired through infection is only, for now, an assumption based on past experience with other viruses. No scientific studies have confirmed this hypothesis yet. Nonetheless – serology testing for antibodies is a critical part of national testing programs.

Antibody testing is generally less complex and certainly more rapid that testing for the virus itself (the PCR test). In fact there are even test kits on the market that are similar to home pregnancy tests. Most kits however, involve the need for a blood sample to be collected with a finger prick, which is then analysed in a lab setting. However, as stated above most of the new tests on the market have bypassed the needed oversight.

The issue is that many of the new tests have a high rate of false positives. This makes sense given the many types of antibodies in our blood stream, with some, such as the common cold corona virus, very similar in structure to the CoVid virus. Of the 12 antibody tests that were studied by the CoVid testing project in the USA, one of the tests gave false positives more than 15% of the time, or in about one out of seven samples. Three other tests gave false positives more than 10% of the time.

It is a work in progress though and some of the larger firms (Roche, Abbot and others) seem to be close to getting full approval by organizations such as WHO, and the FDA. It seems likely that by June 2020, there will be more reliability in antibody testing.

NEW APPROACH – TESTING FOR COVID GENETIC MATERIAL IN BLOOD SAMPLES – In what could be a significant breakthrough is a blood-based test that will be able to detect the virus’s presence as early as 24 hours after infection – before people show symptoms and several days before a carrier is considered capable of spreading it to other people. In other words — around four days before current tests can detect the virus.

The test has emerged from a project set up by the US military’s Defense Advanced Research Projects Agency (Darpa) aimed at rapid diagnosis of germ or chemical warfare poisoning. It was hurriedly repurposed when the pandemic broke out. The new test is expected to be forwarded for emergency use approval (EUA) by the US Food and Drug Administration (FDA) in May 2020.

Like the viral test, the new blood test hunts for the virus’s RNA (Ribonucleic acid) — in this case it is messenger RNA (mRNA). “Target mRNA is part of the immune response to viral infection,” a Darpa representative said. The test needs about 1 ml of blood – thus blood collection would need to be done in a clinical setting. More will be known about this potential test by June 2020.

In summary – testing for the CoVid virus is expanding in scope and the tests are improving in terms of their reliability. However the limitations of the tests must be fully considered in analysing data concerning infection rates and disease mitigation measures.