More on PCR cycles: Less than 3% of specimens positive at 35+ cycles have live virus

1,750 Views | 14 Replies | Last: 5 yr ago by cone
Keegan99
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AG



Most US labs still declare a positive result if viral matter is detected at up to 40 cycles, which is 32x the "magnification" of 35 cycles.

All test results should include the PCR cycle count at which the viral matter was detected.
DadHammer
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AG
This is so crazy. So the plan was just keep replicating until you get the answer you want?
cone
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if you think it's the plague, you want the diagnostic test to be very sensitive

but it's not the plague, at least not for people under 70
DadHammer
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Didn't the latest cdc data say the overall death rate would be about 0.20%. That's not even in the plaques universe.
Keegan99
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DadHammer said:

This is so crazy. So the plan was just keep replicating until you get the answer you want?


There are reportedly labs in the US that use 45 cycles.

That's 1024x the "magnification" of 35 cycles.

This is the risk of using PCR as a diagnostic tool instead of as a confirmation tool upon presentation of symptoms.
RandyAg98
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or worse, as a screening tool in healthy people.
Keegan99
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Exactly.
cone
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the tests were developed and rolled out in the fog of war

if you want to complain about current sensitivity given that this thing is pretty much endemic and survivable, be my guest
cone
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the problem is you want something faster than PCR but sensitive enough to catch active cases (but not too sensitive)

from what I hear, rapid antigen isn't fit for that purpose either
Keegan99
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The test itself is fine. The PCR machine does exactly what we ask of it.

But the policy around the tests, including deciding who to test and assessing the results and making decisions from those assessments, needs re-evaluation.

We're not going to be able to test our way to zero COVID.
RandyAg98
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Right, the false negatives on that thing make it pretty unreliable, if not useless. If you had a fast-turnaround PCR test that only ran the number of cycles needed to detect viable viral loads, then that would be ideal. Sensitive, but not overly so, and very specific.
cone
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you basically use the rapid antigen to get back to work
amercer
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I'm not sure this study say what you guys are implying it says.

From the figure posted all you can really say it that the two assays have different limits of detection.

A study showing that people who are positive at cycle 38 always have mild disease, or are asymptomatic (or even are false positives) would be really interesting.
bigtruckguy3500
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DadHammer said:

This is so crazy. So the plan was just keep replicating until you get the answer you want?
No one is doing this. Manufacturers of the PCR assay do studies on various viruses and bacteria and come up with a general number of cycles to use if you're testing for different things.

Maybe when you test a urine sample you only need 20 samples to detect gonorrhea, but you need 35 cycles to detect chlamydia. Since both tests are typically run simultaneously, you'd probably go with 35 cycles. Does that mean that the extra cycles are detecting clinically insignificant gonorrhea?

Likewise, maybe you need 40 cycles to detect the influenza virus, or RSV. When this was inundating Italy and New York, there was no time to run PCR samples for different cycles and then determine which samples also produce viable virus. I'm sure some manufacturers just turned it up to 11 while others probably used numbers similar to other assays that detect RSV, or flu, or other respiratory viruses.

Also, I don't think this is study necessarily means what it's suggested to mean. We know that infected cells will continue to produce viral RNA even after clearing the virus. And we know that detectability varies depending on where in the infection cycle you are. A positive test with someone on the upslope of infection is very different than a positive test from someone on the downslope, regardless of the Ct used to detect it.

But I do agree that we need to understand the data we're producing before we make policy decision off of it. And we need to be willing to change what we believe as the science develops. A lot of people are saying we shouldn't be testing asymptomatic people, but you know what, Americans love to get tested for stuff, especially when insurance or the government is paying for it. Even if it won't change management, they want testing. And as long as they want it, and someone will pay for it, then the free market will provide it.

But, let's also keep in mind that asymptomatic testing isn't without merit. When Marines went to Okinawa a few months ago, they all quarantined for 2 weeks prior to being released to their regular housing. During those 2 weeks COVID spread throughout, with largely asymptomatic infections, until it stopped being asymptomatic. Over 100 cases in military members, likely contributing to the 2000+ cases in local nationals, and 40ish deaths. On an island with one of the oldest populations in the world, this is kind of a big deal.
DadHammer
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cone said:

the tests were developed and rolled out in the fog of war

if you want to complain about current sensitivity given that this thing is pretty much endemic and survivable, be my guest

You make very little sense sometimes. It's October not February 2020.


cone
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AG
sorry to don't say what you want to hear
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