General Discussion
In reply to the discussion: I talked my wife into not attending the Minnesota State Fair [View all]BumRushDaShow
(137,532 posts)And again, as I noted earlier, the Wisconsin report was not designated "a study". It was their reported data that had background info associated with it, and analysis of what they found with their outbreak.
The "Ct" reference value is used in PCR (polymerase chain reaction) tests that amplify the amount of collected sample through a number of "cycles" to get enough of it to be detected by a fluorometric detector. A bunch of years ago I ran these as part of a couple training courses that I was one of the instructors for. I am sure the instruments today are much more sophisticated than those back then but the concept is the same. I believe the sample gets a marker substance that binds to the molecules that would cause the fluorescence that would eventually get detected.
Basically the more cycles needed to get enough of it to detect, the less there is of the targeted material in that sample. Alternately, the lower the number of cycles needed to detect the marker, the more there is in that sample. Variations will inevitably occur with samples based on the collection techniques and how much was actually collected using the swab, as well as the transfer techniques to preserve that sample for eventual marking, and analysis. I.e., sometimes not enough is collected or something happened between collection and transfer or sample prep that results in getting an "inconclusive" result.
University of Wisconsin describes it here (PDF file) - https://www.wvdl.wisc.edu/wp-content/uploads/2013/01/WVDL.Info_.PCR_Ct_Values1.pdf
In general, across the hundreds of different manufacturers of test kits/schemes, the number of cycles for amplification is generally cut off at ~35.
I posted about the guidance regarding these tests here - https://www.democraticunderground.com/?com=view_post&forum=1014&pid=2778994 and will re-post below -
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FDA publishes a reference standard for the current EUA-approved tests - https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/sars-cov-2-reference-panel-comparative-data
which indicates the minimum detected viral load (particles per ml) for each of the approved test systems. A good summary of that is here -
It can help better triage patients, physician argues
by Robert Hagen, MD January 4, 2021
(snip)
The FDA has given lab manufacturers a wide latitude in determining the cycle threshold cut-off number of their qualitative tests to determine positive versus negative. These tests were approved under Emergency Use Authorization and have not been subjected to typical FDA scrutiny. With this in mind, the state of Florida has required all laboratories doing COVID testing to report the cycle threshold numbers used in qualitative and quantitative tests.
So how does a qualitative RT-PCR test work? Basically, the manufacturer sets the test to turn off the cycling or amplification process when a certain number is hit. For a qualitative test set at 40, after 40 amplification cycles, if any viral material is detected, it turns off and is reported as positive. If none is detected, it would be reported as negative. If the number of amplification cycles was really 15 or 25, it would still run until it gets to 40 and be reported as positive. With these type of tests, it's critical to use an agreed-upon cycle threshold value such as 33 (CDC) or 35 (Dr. Fauci) rather than setting it at a potentially misleading 40 or 45.
Many of the current tests in use are preset by the manufacturer to these higher numbers.The World Health Organization issued a notice last week telling the labs "the cut-off should be manually adjusted to ensure that specimens with high Ct values are not incorrectly assigned SARS-CoV-2 detected due to background noise." Could this be a reason why many people test positive but remain asymptomatic? In that same memo, WHO said all labs should report the cycle threshold value to treating physicians.
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. A test that registers a positive result after 12 rounds of amplification for a Ct value of 12 starts out with 10 million times as much viral genetic material as a sample with a Ct value of 35. Above that level, Fauci has said the test is just finding destroyed nucleotides, not virus capable of replicating.
https://www.medpagetoday.com/infectiousdisease/covid19/90508
(emphasis mine)
The number of cycles (Ct) to reach a detectable amount with forced replication (amplification), tends to vary (due to sampling type and consistency, and obviously due to sample prep required for the various test systems and their actual detector thresholds). But from a bunch of research things that I looked at, some kind of "positive" result will be detectable within a range from ~13 - 35 cycles.
Supposedly many of the test systems are set to run for up to 40 cycles to catch the most minimal of particles, but generally going that far didn't seem necessary. For example, a simple description of that was this (from October 2020 regarding viral shed) -
(emphasis mine)
So looking at the 5 pages of "approved" tests, the most sensitive vs the least sensitive -
180 | PerkinElmer, Inc. | PerkinElmer New Coronavirus Nucleic Acid Detection Kit
600000 | Boston Medical Center | BMC-CReM COVID-19 Test
So the above represents the "lowest detectable" by those systems (as the most sensitive vs the least sensitive for the approved list) but either would be considered a "low" viral load. And within the ranges of each of these tests, there would be a "high" load value that is detected with the minimum amount of amplification cycles, and based on a number of papers, those with "high" loads happen fairly soon in the number of cycle runs, but more often than not, after about 12/13 cycles. And apparently once they hit a "positive", they cease any further runs.
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And with respect to the UK study that you cite, this summarizes what they found - https://www.nature.com/articles/d41586-021-02187-1
But that is not unexpected and it indicates that the vaccine "is working".
Here is a link to that UK study's summary and what it said in the abstract - https://spiral.imperial.ac.uk/handle/10044/1/90800
Discussion From end May to beginning July 2021 in England, where there has been a highly successful vaccination campaign with high vaccine uptake, infections were increasing exponentially driven by the Delta variant and high infection prevalence among younger, unvaccinated individuals despite double vaccination continuing to effectively reduce transmission. Although slower growth or declining prevalence may be observed during the summer in the northern hemisphere, increased mixing during the autumn in the presence of the Delta variant may lead to renewed growth, even at high levels of vaccination.
(the link went to something that was jammed into one big paragraph so I separated out based on where section headers were)
The above regarding the reduced effectiveness over time is also why you see the U.S. and other countries going with the boosters and again, it confirms what was found from the data from Wisconsin and Provincetown - i.e., "fully vaccinated people" were found to be able to contract the virus over time. And in the case of the UK, they were actually testing everyone - both symptomatic and asymptomatic, whereas in the U.S. they are not really tracking asymptomatic infections (unless someone believes they were exposed and gets tested and that result gets reported). So the number of "positives" in the U.S. is probably much higher, but people who have little or no symptoms are generally not getting tested (and have been dissuaded from getting tested).
And with that, some Thomas Dolby (came out my senior year in college and I still have the 45 in a crate somewhere ) -