Story at a glance
- On January 20th, 2021 the World Health Organization published a Medical product alert that testing sites should be manually resetting their PCR cycle thresholds to lower values.
- Higher PCR cycle thresholds detect dead nucleotides of a virus, which are non-replicable and non-contagious.
- Asymptomatic infections and weak positives could be linked to testing sites using too high of thresholds.
Overview of W.H.O.’s statement
On January 20th, 2021 the World Health Organization (W.H.O.) released a statement clarifying that testing sites should be manually resetting the Cycle threshold values on their Polymerase Chain Reaction (PCR) tests.
The released statement is an updated version of a prior release, which was initially published on December 14, 2020.
Their statement is targeted towards labs who use “Nucleic acid testing (NAT) technologies that use polymerase chain reaction (PCR) for detection of SARS-CoV-2″(1)
According to this release of information, W.H.O. felt as if the PCR users were not following the instructions for use accordingly. Prior to this clarification, weak positive results of SARS-CoV-2 were being interpreted incorrectly.
The alert says, “…careful interpretation of weak positive results is needed. The cycle threshold (Ct) needed to detect virus is inversely proportional to the patient’s viral load. Where test results do not correspond with the clinical presentation, a new specimen should be taken and retested using the same or different NAT technology.” (2)
When interpreted, this quote questions the notion that those who test positive for SARS-Cov-2 could be asymptomatic.
What is a Cycle threshold? Why does it matter?
Cycle threshold (Ct) is “…the number of cycles needed to amplify viral RNA to reach a detectable level.”(3)
In other words, Ct values are the metric used in diagnostic testing to reveal whether someone has traces of a virus in their system or not. Typically, a simple ‘positive’ or ‘negative’ result is what is sought from the conclusion of these tests. However, researchers are now revealing the important correlation between Ct values and the viral load within a positive result.
Perhaps the most important aspect of a Ct value is the fact that it is inversely proportional to the viral load (the concentration of virus in blood). Which means that the more cycles it takes to detect viral RNA, the smaller the viral load will be.
Qualitative and quantitative assays
According to Robert Hagen, MD, there are two types of PCRs: qualitative and quantitative.
- Qualitative PCR testing: “Qualitative PCR testing only indicates a simple positive or negative based on the internal cut-off point at which the machine shuts off.”(4)
- Quantitative PCR testing: “A quantitative test is designed to come up with the actual cycle threshold value as the cycling process turns off when detecting any virus. There is not a preset value, so a quantitative measure is obtained.”(5)
The difference between these two tests is vital, as the qualitative PCR test has a pre-set value, whereas the quantitative PCR test immediately stops after any trace of a virus is detected.
The PCRs which were distributed in an act of emergency are presumably under the ‘qualitative’ category, which is why W.H.O. feels so inclined to address the misinterpretation of what the standard Ct value should be.
It has been estimated that the pre-set value of the PCRs has been in the 40s. This means that the machine will continue to operate until it reaches 40 cycles, regardless if viral RNA is detected beforehand.
Dr. Anthony Fauci himself stated in a July 2020 interview with TWiV (This Week in Virology), that “What is now sort of evolving into a bit of a standard, is that if you get a cycle threshold of 35 or more that the chances of it being replication competent are miniscule.”(6)
Fauci then later explains how any ‘detected’ virus from a Ct value higher than 35 is merely a destroyed nucleotide, which is unable to be replicated.
Chances of being contagious while asymptomatic are slim
Conversations revolving around the clinical presentation of patients who tested positive for SARS-CoV-2 and their Ct values are starting to arise.
There is speculation that those who tested positive, yet had Ct values greater than 35, were the patients who appeared to be asymptomatic.
A team of researchers at the Méditerranée Infection University Hospital Institute in Marseille, France, observed the relationship between a patient’s Ct value and their chances of being contagious.
Their investigative process consisted of placing samples (which had tested positive for a SARS-CoV-2 and been through the PCR testing process) on cultures to effectively measure the positivity rate of the culture.
The research says, “Samples with Ct values of 13-17 all led to positive culture. Culture positivity rate then decreased progressively inversely proportional with Ct values, to reach 12% at a 33 Ct value.”(7)
The evidence, according to the researchers, was conclusive enough. They said, “Based on this data, researchers deduced that patients with Ct values > 34 do not excrete infectious viral particles and thus may be discharged.”(8)
Despite popular belief, there is a chance that those who are SARS-CoV-2 positive yet asymptomatic could be non-contagious as well.
Now that the World Health Organization has directly addressed the misuse of PCRs in SARS-CoV-2 testing sites, there is a possibility that we will see the positivity rates decline.
If the testing sites manually adjust their Cycle threshold values to 33-35, then the arrays should only be detecting large viral loads.
Since any viral load detected above a Ct value of 35 is considered a dead nucleotide/weak positive/non-contagious, there is no reasonable explanation as to why PCR tests are still being conducted with these heightened values.
If SARS-CoV-2 testing labs do not manually adjust their Ct values, there is a high chance that patients will continue to receive false positive diagnoses.
If you must get tested for SARS-CoV-2:
- Ask your health care provider if they can request your Ct value from the diagnostic lab. (W.H.O. states that the Ct value should be included in the report back to your health care provider)
- If you test positive, but feel asymptomatic, examine your Ct value. If your Ct value is greater than 35, request a new test to be administered with the manual adjustment of the PCR set to 33.
- World Health Organization, “WHO Information Notice for IVD Users 2020/05: Nucleic acid testing (NAT) technologies that use polymerase chain reaction (PCR) for detection of SARS-CoV-2″.World Health Organization. January 20, 2021.
- World Health Organization, January 20, 2021.
- AACC.org, “SARS-CoV-2 Cycle Threshold: A Metric That Matters (or Not)”, December 3, 2020.
- Hagen, Robert, MD. “Op-Ed: Why PCR Cycle Threshold is Useful in Coronavirus Testing”. MedpageToday. January 4, 2021.
- Hagen, Robert, MD
- Fauci, Anthony, MD. This Week in Virology. 17 July 2020.
- Gupta, Sweta. “Strong Inverse Correlation Between SARS-CoV-2 Infectivity and Cycle Threshold Value”. Infectious Disease Advisor. May 14, 2020.
- Gupta, Sweta. Infectious Disease Advisor. May 14, 2020.