Do you remember how the pandemic scare started in the West? It was the news coming from Italy that freaked everyone out. A report from the Italian public health agency dated March 20, 2020 was released describing the Italian catastrophe. You only have to read the first couple of pages, including the footnotes, to realize it was a scam. And if the first two pages don't do it, then the 5th absolutely will. "For 2 patients under the age of 40 years, no clinical information is available; the remaining 7 had serious pre-existing pathologies (cardiovascular, renal, psychiatric pathologies, diabetes, obesity)." – this is what was said about the COVID-19 deaths.
I did not read that report when it came out. Neither did most of the people. The few who did got ridiculed and ostracized.
Part 1. Potato. PCR, the gold standard
"In Ontario, we use PCR as the gold standard of testing for COVID-19 because it is able to successfully detect tiny amounts of the virus (sensitivity) with a low chance for error (accuracy) compared to other types of lab tests."
— Jonathan Gubbay, Medical Microbiologist, Public Health Ontario
“… able to detect tiny amounts of the virus..” – Jonathan does not give the PCR technology enough credit. It is not only capable of detecting tiny amounts of virus but tiny amounts of the virus parts, like molecules. Polymerase Chain Reaction (PCR) is an amazing invention. Kary Mullis, who invented the PCR method in 1985, was recognized for this achievement by the Nobel Prize in Chemistry in 1993.
It would be very interesting to hear Kary’s opinion on the “gold standard” in the context of today’s PCR application but, sadly, he died in 2019 just before COVID-19 and the pandemic were announced. Mullis did say though
“… with PCR, if you do it well, you can find almost anything in anybody… If you can amplify one single molecule up to something that you can really measure – which PCR can do, there is very few molecules you don’t have at least one single one of them in your body... It [PCR] allows you to take a very miniscule amount of anything and make it measurable and then talk about it in meetings and staff like it’s important. That’s not a misuse, that’s just a sort of misinterpretation of [PCR]. It [PCR] does not tell you that you are sick…”
While this was said in the context of HIV, it casted a shadow of a doubt on PCR-based diagnosis for all viral ctitters, including SARS-CoV-2.
Mullis’s legacy sparked controversy resulting in claims by Science™ deniers that PCR is useless for diagnosing COVID-19, followed by respective Fact Checkers debunking all those “racists” and “misogynists”.
But why would there be even a slightest controversy for such an amazing technology without which e.g. the “Human Genome” project would not be even possible? Solving this puzzle needs answering the following question first.
What does it mean to diagnose someone as sick with COVID-19?
For someone to get sick, he needs to have viral culture in loads sufficient to evoke symptoms and transmissibility, or capable of developing into such loads. The key phrase here is “viral culture”. A mere detection of viral parts is irrelevant to proclaiming someone as “having COVID” or sick.
The Government of Canada gives us a very good perspective on that: “The genetic fingerprint of the virus can be picked up long after the virus is no longer infectious. PCR can be positive for over 100 days or more after infection...”
I took advantage of this aspect, which also made it into travel policies. When I had to travel in 2022, and wanted to avoid all the COVID testing hassle at the airports. For $150, an online doctor issued “COVID recovery letter”, and that piece of paper gave me 180(!) days immunity (pun intended) from COVID testing.
So, if you had COVID in the winter and then later in the early summer suffered from your regular hay fever episode, a just-in-case PCR might surprise you with “re-infection”.
Another revealing example of PCR’s finding too much is with varicella-zoster virus (VZV). VZV causes Chickenpox, and it also causes shingles. After recovering from chickenpox, the virus remains in the body (dormant) and can cause shingles if VZV reactivates later in life (e.g. if immune systems gets compromised). People with shingles can then spread VZV to people who have never had chickenpox or never received the chickenpox vaccine. The presence of varicella virus is best detected by… you guess it.. PCR test. Mind that shingles is much worse and chickenpox is roughly 3 times more contagious than COVID-19. But while many people had chickenpox in their childhood and hence have the varicella-zoster totally capable virus culture "living" inside them, it would be ludicrous to suggest that those people are sick or contagious and must be quarantined. But, that’s what PCR would indicate, if applied in the same manner as for detecting SARS-CoV-2. And the testing is done on the blood, which gives much more reliable sampling compared to collecting droplets in a human’s respiratory tract. So, even the presence of viral culture does not mean “infection” if your immune system keeps it in check.
How about taking a perfectly healthy person with no particular symptoms and swabbing inside of his nose? If the culture shows the presence of staphylococcus aureus, do we proclaim staph infection?
So, detecting virus is by far not the same as detecting the disease it causes, and even less so for any parts of the virus.
How does PCR testing discern a viable viral culture from harmless virus debris?
This might surprise Jonathan Gubbay, Medical Microbiologist of Public Health Ontario, cited earlier, but PCR method does NOT detect viruses per se – it deals with DNA or RNA molecules. COVID-19 PCR test, through a series of temperature changes and application of polymerase enzyme, makes copies of RNA molecules of interest (commonly targeting regions in the SARS-CoV-2 gene encoding the spike (S) protein). Each temperature cycle doubles the number of the RNA molecules present, until their amount reaches a certain detectable threshold. And the number of the cycles it takes for the PCR machine to reach such a threshold is called Ct (Cycle Threshold). The more initial RNA of interest there is, the fewer cycles it takes to detect that significant amount. A low Ct number means that the target molecule was present in high amounts, while a high Ct number means it was present in low amounts.
The conclusion (or rather a probabilistic estimate) whether a viral culture is present or not is done by limiting the number of PCR cycles not to exceed a certain predetermined Ct value, and if the generated RNA amount reaches the significant threshold within the set number of cycles, it is assumed that the test is “positive” and the viral culture is indeed present.
So, what is the magic PCR Ct cut-off number?
A number of studies have been conducted to determine the right Ct cut-off number that would nail the presence of infection (viable viral culture) reliably, meaning, with the least number of false positive and false negative outcomes. However, this field remains wide open to different opinions and completely opposing views on the use and communication of Ct in general and its cut-off value specifically. Here are two articles from serious sources arguing respectively for and against paying attention to and reporting Ct values in PCR testing – just to give you a sense of how messy and unsettled this subject is.
· “CT values could also help clinicians flag patients most at risk for severe disease and death.” (Science, “One number could help reveal how infectious a COVID-19 patient is. Should test results include it?”)
· “The utilization of Ct values to guide patient management is discouraged. Correlation with viral load, viral burden, or infectivity has not been established for qualitative SARS-CoV-2 tests.” (AACC, “How to Say No to Reporting Ct Values”)
“An Overview of Cycle Threshold Values and their Role in SARS-CoV-2 Real-Time PCR Test Interpretation” article by Public Health Ontario offers a lot of great information about Ct and its application in Canada. According to the research quoted in it, “specimens with Ct values > 24 were viral culture negative. However, the US CDC has reported that they were able to culture virus from specimens with Ct values up to the low 30s (unpublished data)”.
Even if we trust the unsubstantiated CDC claim (why wouldn’t we?), what this still tells us is that from Ct=25 and up to 30 things get quite problematic for declaring infection. And if we go above 30 and into mid/high 30’s the chances of the positive PCR to be representative of a viral culture (infectious disease) are slim to none, meaning, a positive PCR test with Ct > 30 is most likely a false positive infection-wise.
A French research group’s extensive study on this subject has shown that:
at Ct of 25, PCR test resulted in 30% of false positives (30% positively tested samples were not infectious);
at Ct of 30, 80% of false positives;
at Ct of 35, 97%;
and at a Ct above 35, no sample remained positive (infectious) in cell culture (100% false positives).
So, branding someone “COVID positive” at Ct above 30 (without further testing or analyses) would be moronic, and above 35 - criminal.
But, what are the cycle threshold (Ct) cut-off values used in Canadian labs?
The answer is not an easy find. The aforementioned Public Health Ontario article has a whole section explaining “Why aren’t cycle threshold reported on test results?”. Apparently, “like with other PCR tests (including non-COVID-19 tests), it is not recommended to provide Ct values on test results in Ontario (and Canada). PCR tests tell us if the virus is present or not in the sample provided to the lab; however, there are other factors to consider in interpreting lab results. Ct values are not directly comparable from one PCR test kit to the next, and can change with increased transportation times, sample storage conditions, and sample collection method.” I am sure that “other factors” are important, but every cycle doubles the amount of the object, and the impact of incrementing Ct is hard to overestimate. Also, the lab technicians go through the pre-established routine and give people their tests back, positive or negative with no “factors” to consider and no Ct information on them.
And again, the very same helpful article comes to rescue! “At PHO, Ct values are available to health care professionals upon request, and low level detected results (Ct value 35 to 38) are indicated on the laboratory report (since November 2020). There is still a lot to learn about Ct values and more research is required to fully understand Ct values and their link to disease onset, severity and infectiousness.” From that statement it is obvious that the Ontario labs run PCR tests at least up to Ct=38.
What about the repercussions from false positive results that would obviously follow from such high thresholds (Ct)?
A Lancet study that looked into such rather obvious repercussions offers the following list (abridged and highlighted by me):
Individual perspective:
For swab tests taken for screening purposes before elective procedures or surgeries: unnecessary treatment cancellation or postponement
For swab tests taken for screening purposes during urgent hospital admissions: potential exposure to infection following a wrong pathway in hospital settings as an in-patient
Financial losses related to self-isolation, income losses, and cancelled travel, etc.
Psychological damage due to misdiagnosis or fear of infecting others, isolation, or stigmatisation
Global perspective:
Misspent funding (often originating from taxpayers) and human resources for test and trace
Funding replacements in the workplace
Epidemiological and diagnostic performance
Overestimating COVID-19 incidence and the extent of asymptomatic infection
Misleading diagnostic performance, leading to mistaken purchasing or investment decisions
Misdirection of policies regarding lockdowns and school closures
Increased depression and domestic violence
"Most samples that test positive at PHO are found after a low number of cycles are run. However, any indication of the virus in a sample is important, regardless of how many cycles it took to find." — Samir Patel, Clinical Microbiologist and Deputy Chief Microbiology, Public Health Ontario
Samir thinks that it’s better to test with as many cycles as it takes to find “any indication of the virus”. Why? Just to prove that PCR, according to its inventor, “can find almost anything in anybody”? Did he consider what such practice leads to?
It should be clear that testing at Ct=38 or higher (which is likely the case) does produce false positives, and anything COVID positive over Ct=30 is almost guaranteed to be a non-infectious case.
And how many or what proportion of all reported cases do fall in that “Ct > 30“ bucket?
Again, there is no easy answer. Our most helpful Public Health Ontario article need to be invoked again. “How commonly this [false positive] occurs in the province is not known, as individual reports that are corrected are not centrally documented”. PHO admits that this information is not collected. However, in the very same paragraph it claims that “Based on PHO Laboratory data, the rate of false positive tests that are later determined to be negative requiring results to be corrected is extremely low.” They purport a rate “of less than 0.01%” based on admittedly occasional, not formalized reporting of the PCR false positives, while emphasizing the need to run as many cycles as it takes to get to the positive... And this seems to be the only “science” we have on the matter in Canada.
However, a German study re-analyzed PCR tests of 160,000 people and concluded: “In light of our findings that more than half of individuals with positive PCR test results are unlikely to have been infectious, RT-PCR test positivity should not be taken as an accurate measure of infectious SARS-CoV-2 incidence. Our results confirm the findings of others that the routine use of ‘positive’ RT-PCR test results as the gold standard for assessing and controlling infectiousness fails to reflect the fact that 50-75% of the time an individual is PCR positive, they are likely to be post-infectious.” Read it again!
50-75% false positives in a randomly sampled PCR-tested people!
So much for the “gold standard”. And that’s in Germany, where Ct cut-offs were likely lower than in Canada (due to surprising lack of information on this subject in Canada, it is assumed that Canada labs’ practices were similar to the US, where CDC advised for Ct cut-off to be at 40, while many European labs work with 30 to 40 cycles)
And some final food for thought. Before 2020 Canada was reporting about 50,000 cases of influenza annually (counted seasonally from Sep to Aug). According to the Government of Canada FluWatch report, only 69 influenza detections were reported for the 2020-2021 season. Total flu elimination in 2020-21 is sometimes attributed to lockdowns and other measures (masking, distancing, school and workplace closures, etc.) introduced to slow down the COVID-19 pandemic. However, that hypothesis is busted by countries and states that exercised much lighter approach to COVID containment but had virtually no flu either. For example, Sweden response to COVID-19 containment in the period, corresponding with 2020-2021 influenza season, was very modest and did not go beyond merely recommending to stay home, had no school or workspace closures, and had no masking policies at all. Nevertheless, it seemed to have been enough to eliminate flu to the same extent as it happened in Canada amounting, according to The Public Health Agency of Sweden “Influenza in Sweden – Season 2020-2021" report, to only 29 sporadic cases of laboratory-confirmed influenza…". While an argument can still be made that influenza viruses have been displaced by the more infectious novel coronavirus, it might be better ascertained by analysing Ct numbers of the PCR positive patients with flu-like and no taste loss symptoms.
There can be a lot more said about PCR testing and the circumstances of its misapplication in passing the COVID-19 positive/negative judgement (this petition can be a good resource for curious and scientifically inclined minds), but the main point of this article is how much such a misapplication contributed to defining the state of the world as in pandemic. And if it’s 75%, it seems like a lot, and for Canada and the USA specifically, 75% might be an understatement.
And now onto the second ingredient of this simple recipe: