A scientific analysis of the Public Health Agency of Canada's PCR test recommendations to the provinces.
In the summer of 2022, The Canadian Independent filed a freedom of information request with the Public Health Agency of Canada with respects to recommendations provided to the provinces and territories on Covid-19 PCR testing. Those documents are available for viewing below or here.
The above documents were sent to Dr. David Speicher, a molecular virologist and clinical epidemiologist in Hamilton, Ontario for review. He examined the recommendations and wrote a report. That report is provided below.
REPORT: Before I summarize the data in the FOIR and provide supplementary information I want to bring attention to a presentation that I gave to the CCCA on the detection of COVID including PCR, RATs, and COVID sniffing dogs. The last link is a prestation by Dr. Bridle at an event in Wellandport in November 2021 on the RATs using data that I brought to his attention.
Rapid Antigen Tests (RATs)
We knew when they were first released that RATs should never have been used for diagnostic screening, especially in asymptomatic (i.e. healthy) people. RATs are highly insensitive with a limit of detection of 100,000 viral copies/mL (Ct 23-25; sensitivity 84.3% (79.5% to 88.1%). When compared to the PCR test 83% of tests had viral loads below 100,000 viral copies. Therefore, the RATs should only have ever been used for quick screening of symptomatic patients. Even the PHAC report, CCDR January 2021 Vol. 47 No. 1, recommended that RATs only be used for symptomatic patients because the viral load was not high enough to give a positive RAT result until 1 day before symptom onset. The only reason that Ontario used RATs en masse was because for the Delta variant viral load peaked 2-3 days prior to symptoms. However, this tend has not been seen since the Delta variant and RATs should not be used unless a person has symptoms.
The social media phenomena of the false positive Panbio RATs was a mystery until I saw the data in the FOIR. The data clearly shows that while the BD Veritor appears to work correctly, the most commonly used RAT, the tests that the Ontario Government handed out, are the Panbio and the BTNX Rapid Response. Based on the FOIR there is clear evidence that the Panbio RAT does not perform adequately and should never have been used for asymptomatic testing. In the Panbio test there is nonspecific binding between the conjugate and capture antibodies if the pH of the sample added to the cartridge drops below 7.0 or if the Tricine concentration drops below 100mM. Tricine is an organic compound derived from Tris and glycine used in the buffer solutions. This is why the data shows a false positive result when a range of buffers and transport media as well as food and water samples are added neat to the RATs. While the data shows that there should not be a problem if the tests are used correctly, i.e. used as per the package insert ensuring that a proper sample and adequate buffer is mixed, the Panbio test is not recommended for asymptomatic testing for entering a workplace or long-term care facility and any result should only be considered a “probable” result and needs to be confirmed with the more sensitive and reliable PCR test. The problem with the Panbio kit is that the buffer comes in a bottle that must be dispensed by the “number of drops” for each test. If the buffer expires, gets contaminated, or is not measured correctly (e.g. too many or too few drops used) there is a risk of a false positive result. Based on the data in the FOIR I am amazed that these tests were even distributed for use especially as PHAC knew of the false positive results and tried to hide the truth from the public.
Nucleic Acid Tests (PCR)
The information regarding PCR testing and Ct values as found in the FOIR makes complete sense. Dr. Neil Rao (Medical Microbiologist, Halton Hills) and I are writing a comprehensive review on the PCR detection of COVID, but I will summarize this issue here. There is “misinformation” on both sides of the narrative regarding PCR testing. The PCR assay is a powerful and very sensitive test that can only answer this question. “Is this known RNA/DNA sequence present in this sample?” The assay cannot tell if the virus detected is whole in-tact infectious virion or non-viable debris. The problem with the “high Ct value” argument and asking how many cycles the PCR is run for is that it is not number of cycles that the assay is run for that counts but the validated cut-off Ct between a positive and a negative result. It is often misquoted that the PCR test produced “97% false positives” but no one has been able to provide me a reference for this. However, Borger, Malhotra, and Yeadon et al stated that “If someone tested positive by PCR as a threshold of >35 the probability that said person is actually infected is <3%, the probability that said result is a false positive is 97%”. They did not say that the PCR assay was not reliable, but that any result Ct >35 is most likely a false positive. This is because the limit of detection for most validated PCR assays is between Ct 35 and 37 or ~100 copies. Any test that is used beyond the limit of detection is never reliable.
The biggest problem with how the PCR test was used is that (i) we should never have tested asymptomatic/healthy people and (ii) the definition of a COVID case.
1. Testing Asymptomatic People
Symptoms develop when the viral load is Ct 25-27, which is similar to the load required to grow in culture. Viral loads below this (i.e. Ct >27) is not high enough to produce symptoms and is not high enough for transmission to occur. The use of PCR on so many asymptomatic people has never been done before COVID. Pre-COVID PCR has only been on symptomatic sick people to determine the aetiological agent of infection.
2. The definition of a COVID case
There needs to be a clear definition of a “COVID case”. The PCR assay detects the presence of SARS-CoV-2 RNA in a sample. A negative sample is only presumptive negative unless there are symptoms. There needs to be clear distinction between those who are virus infected, asymptomatic, and NOT infectious and those with symptoms who are infectious. You cannot say that a person has COVID unless they have symptoms, yet public health is using PCR positive tests to presume a COVID positive case regardless of symptoms. PCR positivity prior to symptoms can only suggest that if symptoms develop over the next few days that the person develops COVID. While a person can test PCR positive 2-3 days presymptomatic they are only able to transmit the virus once viral load is high enough to cause symptoms, i.e. when the person develops COVID. However, after day 8 the person enters into convalescence where the viral load is reduced, the virus is being shed as debris yet symptoms remain due to the damage caused. During this time a person may test PCR positive at low viral levels (Ct >30) for up to 3 months. At this time, if someone tests 4 times over a week and are positive all 4 times at low viral loads that is recorded as 4 COVID cases despite being only 1 case. We cannot solely rely on PCR cases to determine the numbers of COVID and there needs to be better communication between the diagnostic laboratory and the bedside clinician.
Ct values are rarely given to the clinician because most do not know what to do with the information. The only information that is given to the clinical is positive/negative PCR result. The problem with Ct values is that you cannot compare results between labs solely by Ct values. Ct values are completely dependant on the sampling, extraction, amplification and detection method. Even slight changes in time of collection (i.e. days pre and post symptoms), pipetting errors, or the PCR machine used to test samples can slightly alter the Ct value, which is why they are not released to the clinician.