For more than a year the reverse‐transcriptase polymerase chain reaction (RT‐PCR) test for viral load has been considered a “gold standard” in the diagnosis of CCP/CoVid-19 infection.
Should it be?
RT-PCR is a laboratory technique combining reverse transcription of RNA into DNA and amplification of specific DNA targets using polymerase chain reaction. This technique’s “transformation and amplification” process infers the amount of a specific RNA by monitoring the amplification reaction using fluorescence. Real-time PCR or quantitative PCR (qPCR) are commonly used for analysis of gene expression and quantification of viral RNA in research and clinical settings.
However, the amplification process has its drawbacks. The well-described long tail of RNA positivity after the transmissible stage means that many, if not most, people whose infections are detected during routine surveillance using high-analytic-sensitivity tests are no longer infectious at the time of detection (Mina et al., 2020). Depending on when the test is taken, one could have a positive result and yet be in the post-infectious stage.
A particularly high Ct count further expands the response curve to include larger fractions of post-infectious load.
As reported in The New York Times, most than 50% of infections in Massachusetts and New York identified by PCR-based surveillance had PCR cycle threshold values in the mid-to-upper 30s, indicating low viral RNA counts. Thousands of people are being sent to 10-day quarantines after positive RNA tests despite having already passed the transmissible stage of infection (Mandavalli, 2020).
The exponential growth of the reverse transcribed complementary DNA (cDNA) during the multiple cycles of PCR produces inaccurate end point quantification due to the difficulty in maintaining linearity (Gettemy and Gold, 1998). Combined with detecting post-infectious conditions,
RT‐PCR may also increase the positivity rate, depending on the number of repetitions of this test.
Thus, knowing the cycle number (Ct) is crucial to an accurate and reliable CoVid diagnosis. Per Umemneku et al. (2019), RT-PCR tests are NOT the gold standard.
It is crucial to evaluate diagnostic accuracy studies, analytical validity, and testing for agreement in CT, RT‐PCR, and antibodies tests at the different clinical stages. For the moment, and whenever possible, it is more useful in clinical practice to evaluate tests by several methods because there is no generally accepted reference standard.
Off-Guardian (OG) picks up the “test accuracy” trail by observing the rapid fall-off in CoVid positive tests since January 2021 (see https://off-guardian.org/2021/02/26/coronavirus-fact-check-10-why-new-cases-are-plummeting/)
Why the sudden fall-off in case?
Well, Trump isn’t president – sorry, couldn’t resist that one. But interesting timing coincidence anyway.
But why indeed?
As OG observes:
- It’s not the vaccines – not even a tenth of the population has been vaccinated while the drop is happening simultaneously in different countries all around the world, and not every country is vaccinating at the same rate or even using the same vaccine.
- It’s not the lockdowns – “Sweden, famously, never locked down at all. Yet their “cases” and “Covid related deaths” have been dropping exactly in parallel with the UK”
So why?
Well, here’s OG’s take, referring to the graph on the top of the page:
As you can see, the global decline in “Covid deaths” starts in mid-to-late January.
What else happened around that time?
Well, on January 13th the WHO published a memo regarding the problem of asymptomatic cases being discovered by PCR tests, and suggesting any asymptomatic positive tests be repeated.
This followed up their previous memo, instructing labs around the world to use lower cycle thresholds (CT values) for PCR tests, as values over 35 could produce false positives.
OG concludes:
What we’re seeing is a decline in perfectly healthy people being labelled “covid cases” based on a false positive from an unreliable testing process. And we’re seeing fewer people dying of pneumonia, cancer or other disease have “Covid19” added to their death certificate based on testing criteria designed to inflate the pandemic.
Just as we at OffG predicted would happen the moment the memo was published.
There may be other factors, such as the seasonality of solar exposure.
But that’s for another post.
References:
Gettemy JM, Ma B, Alic M, Gold MH (February 1998). “Reverse transcription-PCR analysis of the regulation of the manganese peroxidase gene family”. Appl. Environ. Microbiol. 64 (2): 569–74. doi:10.1128/AEM.64.2.569-574.1998. PMC 106084. PMID 9464395.
Mandavilli, A. (2020, August 29). Your Coronavirus test is positive. Maybe it shouldn’t be. The New York Times. Retrieved from https://www.nytimes.com/2020/08/29/health/coronavirus-testing.html
Mina, M. J., Parker, R., & Larremore, D. B. (2020). Rethinking covid-19 test sensitivity – A strategy for containment. The New England Journal of Medicine, 383(22), e120.
Umemneku Chikere CM, Wilson K, Graziadio S, Vale L, Allen AJ. Diagnostic test evaluation methodology: a systematic review of methods employed to evaluate diagnostic tests in the absence of gold standard—an update. PLoS One. 2019;14(10):e0223832. https://doi.org/10.1371/journal.pone.0223832
Econophysics2020 