5000 shades of grey

You think a Covid-19 test is black and white? Think again.

– by B. Smallwood –

The glory which is built upon a lie soon becomes a most unpleasant incumbrance. How easy it is to make people believe a lie, and how hard it is to undo that work again! – Mark Twain

The place to start is the test. For without a reliable test to determine who is or isn’t infected by a pathogen that’s circulating the world, shutting down societies and economies, and paralyzing normal existence, then we’ve got nothing.

But what do we know about the test that determines whether the virus, SARS-CoV-2, causes the respiratory disease, COVID-19? And further, is that test reliable and being used responsibly enough to support the world’s massive response to this pandemic?

It all starts with a simple question: Does x cause y?

A set of rules known as Koch’s postulates, established in the late 19th century, basically states that if a particular bacteria is the cause of a given disease then the following must be true: the bacteria must be present in every case of the disease, and be able to be isolated from the host carrying the disease, and grown in pure culture. When you put that bacteria into a healthy host, it must reproduce the specific disease and the bacteria must be recoverable from the experimentally infected host. Four simple rules right? How do they apply?

Only with serious mental acrobatics can you say that COVID-19 follows these principles. The problem is that we live in a world with lots of viruses and lots of coronavirus as well. In the case of SARS-CoV-2, no one has produced sufficient evidence to show the so-called “novel” coronavirus satisfies all (or even any) of Koch’s rules. We therefore have no certainty that this virus causes this particular respiratory disease. Apparently this doesn’t really matter because the world’s public health leaders have almost universally agreed that SARS-CoV-2, causes respiratory disease and sometimes death. End of story. The result is a program of testing, tracking, tracing and isolating to keep those infected from infecting others.

So it comes down to the test

The test currently in use in most places in the world is called RT-PCR which uses an enzyme called reverse transcriptase to take a piece of RNA and turn it into a piece of DNA. The PCR (polymerase chain reaction) can turn that DNA into billions of copies of the sample. A fluorescent signal attached to it, if amplified enough, shows up as a positive test.

To amplify the samples so they can be detected, they are heated and cooled in cycles. A cycle threshold, or Ct value, is the number of cycles performed that allows the fluorescent signal to be detected. (For details check out this paper from the Centre for Evidence Based Medicine.

A person gives a nose swab, and that sample is sent off to the lab and the lab comes back with one of two answers: yes – a positive test, or no – a negative test. It’s that black and white. It is certainty. It is the basis of the entire regime of public health measures being employed around the world. The problem is that there is no black and white, only shades of grey.

Problems with the test

The first problem is that we might not be testing the right thing. Researchers around the world were given the RNA sequence of the virus from the Chinese right at the beginning of the pandemic, but is it possible that they didn’t hand over the right thing? Sure it is – and numerous things could also have contaminated that sample along the testing highway.

Then there is the problematic issue of the cycle threshold (Ct). At what point do you draw the line to determine a positive test? At 25 cycles? At 30 cycles? At 45?

In BC, much like other jurisdictions, they run the sample through about 35 cycles, and sometimes more than 40. The problem here, identified by molecular biologists, is that doing this many cycles creates background flourescences. When the virus is discovered at a lower number of cycles it is likely to mean a person is more infectious.

What is also really interesting is that if you do over 30 to 35 cycles, you can’t culture a live virus from the sample. Back to Koch’s postulate: if x causes y, there is a causal connection enabling you to reproduce the disease from the sample. Using such a high cycle threshold means you’re likely finding fragments that are meaningless and say nothing about the infectivity of the patient.

The PCR test amplifies any viral material, including particles that aren’t viable, or capable of being transmitted, or capable of causing disease. So a person with a positive test but no symptoms is, contrary to what most people believe, unlikely to infect others. They are what you call a “cold” positive. They might have had contact with the virus, but they aren’t themselves infectious.

Yet, by setting the Ct at such a high level, the tests are likely spitting out mostly false positives, resulting in directives to isolate and quarantine, and otherwise telling healthy people that they are sick and a risk to others.

A recent systematic review from the UK challenged the value of the PCR test. It said that without routinely testing it against reference and culture specimens, no one really knows how reliable and useful it is. The test doesn’t reveal the one thing you really need to know: does this person’s nose swab tell us anything about how infectious that person is?

Currently there is no viable international standard of reporting how well the tests are working and whether those stamped as positive are actually infectious or not. And yet we are shutting down whole societies on the basis of this test.

Let’s face it. BC has very little of the COVID-19 virus, but we are testing a lot. Back in July, Dr. Barbara Yaffe, Ontario’s Deputy Chief Medical Officer told the media: “If you are testing in a population that doesn’t have very much COVID, you’ll get false-positives almost half the time. That is, the person actually doesn’t have COVID, they have something else, they may have nothing.”

Yet everyone wants to get tested, and as we ramp up testing, and label more and more people as positive we may not be doing ourselves any favours. Regardless of whether you ascribe to the second wave theory, the current epidemic of testing is scaring the bejesus out of the population with a test delivering false positives or positives that aren’t actually infectious to others. This is what you’d call a casedemic, not a pandemic.

There are thousands of shades of grey about this virus, but is it not possible that all the extreme measures we’re taking – the physical distancing, hand washing, mask wearing and locking down communities – is little more than an anaphylactic reaction to a virus?

B. Smallwood is a pseudonym for a BC health policy researcher.

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