PCR False Positives?

[javadog]

Originally Posted by Sooner or later

What is with the name calling and attack? You made the claim. It is up to you to offer proof of said claim.

Feel free to disregard my claim, there’s no prize for winning an argument on the Internet.

The vast majority of my posts are on the 911 technical forum. After dispensing advice for 10 years there, I grew tired of answering the same question a dozen or two dozen different times, which is why one day I decided to walk away from that forum and spend some time here.

Guess what? I’m not going to spend any time rehashing arguments I had here a year ago, with someone that hasn’t stayed up to speed on the topic. I have found that to be a complete waste of my time.

This entire forum is a complete waste of time, for the most part. I anticipate departing for more productive pastures in the near future.

[cabmandone]

Originally Posted by 1990C4S

That's okay for some people; this person operates on children, some of whom are immuno-compromised. A slightly higher bar is required for a Dr, no?

Keep us posted if they give you any updates. I'd like to know what happened if they share that with you.

[javadog]

Originally Posted by 1990C4S

That's okay for some people; this person operates on children, some of whom are immuno-compromised. A slightly higher bar is required for a Dr, no?

I would certainly encourage any healthcare professional to take whatever precautions they deem necessary to do their job safely.

I would also expect any healthcare professionals to be well informed on this issue and not rely on argumentative Internet forums such as this one for their continuing medical education.

[cabmandone]

Originally Posted by javadog

Feel free to disregard my claim, there’s no prize for winning an argument on the Internet.

The vast majority of my posts are on the 911 technical forum. After dispensing advice for 10 years there, I grew tired of answering the same question a dozen or two dozen different times, which is why one day I decided to walk away from that forum and spend some time here.

Guess what? I’m not going to spend any time rehashing arguments I had here a year ago, with someone that hasn’t stayed up to speed on the topic. I have found that to be a complete waste of my time.

This entire forum is a complete waste of time, for the most part. I anticipate departing for more productive pastures in the near future.

Well hell! I'd think since you had them elsewhere that retracing your footsteps wouldn't be hard to do. That is unless what you were saying back then was unsupported nonsense too. Entirely possible I suppose.

[Sooner or later]

I did find this...

https://www.thejournal.ie/factcheck-pcr-tests-irish-video-5304097-Dec2020/

“You get a lot of false positives because you start to identify things that are nothing to do with the current infection,” Dr Carroll said. “It might be fragments of DNA from other coronaviruses.” This happens because the original sample is amplified “through too many cycles”, he added.

Dr Carroll, who has a master’s degree in public health medicine, says that a positive PCR test does not correspond to an active case of Covid-19.

Experts in PCR contacted by  TheJournal.ie  viewed the 97% figure for false positives as a misunderstanding.

“This is not true. This demonstrates a clear misunderstanding of the PCR primers,” says Michael Mina, a professor at the Harvard T.H. Chan School of Public Health.

Primers are the reason why the PCR test for SARS-CoV-2 will only pick up that specific virus and not any other coronaviruses.

“When setting up a PCR test, you need to know what you are looking for, otherwise you won’t amplify anything,” says Dr Cillian De Gascun, director of the National Virus Reference Laboratory in UCD.

Verdict

The video is wrong that the PCR test for SARS-CoV-2 gives a false positive rate of 97%. Also, PCR tests do not wrongly confuse genetic material from other viruses with SARS-CoV-2.

The scientific consensus is that PCR tests are the best option for public health screening right now.

Dr Cillian de Gascun of the National Virus Reference Laboratory in UCD says the actual false positive rate is between 0.1% and 0.2%.

As a result, we rate the claim that PCR tests have a 97% false positive rate as FALSE.

As per our verdict guide, this means: The claim is inaccurate.

[1990C4S]

Originally Posted by javadog

I would certainly encourage any healthcare professional to take whatever precautions they deem necessary to do their job safely.

I would also expect any healthcare professionals to be well informed on this issue and not rely on argumentative Internet forums such as this one for their continuing medical education.

I'm not a healthcare person in any way, I was just wondering about the fallibility of the tests, and the probability of new variants causing a problem for vaccinated people.

At no time did I ask for advice on him returning to work, I'm sure Harvard can look after that.

[javadog]

Originally Posted by cabmando

Well hell! I'd think since you had them elsewhere that retracing your footsteps wouldn't be hard to do. That is unless what you were saying back then was unsupported nonsense too. Entirely possible I suppose.

Something preventing you from doing a search?

Fingers all broken and you’re not dexterous with your toes?

[javadog]

Originally Posted by 1990C4S

I'm not a healthcare person in any way, I was just wondering about the fallibility of the tests, and the probability of new variants causing a problem for vaccinated people.

At no time did I ask for advice on him returning to work, I'm sure Harvard can look after that.

I’m sure he can figure it out for himself.

I wish him good fortune.

[Sooner or later]

Originally Posted by javadog

Something preventing you from doing a search?

Fingers all broken and you’re not dexterous with your toes?

I did a search. Mine find says your 97% is false.

Do you have any support for your claim?

[javadog]

Originally Posted by Sooner or later

I did a search. Mine find says your 97% is false.

Do you have any support for your claim?

Hey, believe what you want. If you think the false positive rate is between 0.1% and 0.2%, as your clip suggests, I can’t help you.

[cabmandone]

Originally Posted by javadog

Something preventing you from doing a search?

Fingers all broken and you’re not dexterous with your toes?

There is! My bullsh.t meter is pegged and it's keeping my computer from working properly. Weird huh?

[cabmandone]

Originally Posted by javadog

Hey, believe what you want. If you think the false positive rate is between 0.1% and 0.2%, as your clip suggests, I can’t help you.

You could help him... if you were only able to find that super secret information that doesn't appear anywhere on the internet. You go dark web?

[Sooner or later]

Originally Posted by javadog

Hey, believe what you want. If you think the false positive rate is between 0.1% and 0.2%, as your clip suggests, I can’t help you.

Yes, you COULD help. Post your supporting documentation of a 97% false positive rate.

[cabmandone]

Originally Posted by 1990C4S

I'm not a healthcare person in any way, I was just wondering about the fallibility of the tests, and the probability of new variants causing a problem for vaccinated people.

At no time did I ask for advice on him returning to work, I'm sure Harvard can look after that.

I did a lot of research on testing back when DeWine had his "I'm positive... WAIT! No I'm not" last summer. The most reliable is considered the PCR which is supposed to have an accepted error rate of somewhere around 25% but that's on the false negative side. On the false positive side it's supposed to be between .5 and 1% or something like that. I could link some stuff that I have bookmarked on testing but it's really not all that exciting.

As I said in my first reply, the vaccine isn't a guarantee you don't get the virus. There is still a chance you can get it but you're supposed to get a less severe case if you do get it. Again, keep us posted and sorry for muddying up your thread with the argument about testing accuracy. I'll stop now.

[brainz01]

Java's on point as usual. For the lazy, here's an article from the toilet Paper of Record -- emphasis mine.

And BTW, different countries use various cycle thresholds for positivity which makes comparison of COVID statistics amongst nations with non-identical standards difficult.

NYT; Aug 29, 2020; Updated Jan 19, 2021
https://www.nytimes.com/2020/08/29/health/coronavirus-testing.html

Your Coronavirus Test Is Positive. Maybe It Shouldn’t Be.
By Apoorva Mandavilli

The usual diagnostic tests may simply be too sensitive and too slow to contain the spread of the virus.

Some of the nation’s leading public health experts are raising a new concern in the endless debate over coronavirus testing in the United States: The standard tests are diagnosing huge numbers of people who may be carrying relatively insignificant amounts of the virus.

Most of these people are not likely to be contagious, and identifying them may contribute to bottlenecks that prevent those who are contagious from being found in time. But researchers say the solution is not to test less, or to skip testing people without symptoms, as recently suggested by the Centers for Disease Control and Prevention.

Instead, new data underscore the need for more widespread use of rapid tests, even if they are less sensitive.

“The decision not to test asymptomatic people is just really backward,” said Dr. Michael Mina, an epidemiologist at the Harvard T.H. Chan School of Public Health, referring to the C.D.C. recommendation.

“In fact, we should be ramping up testing of all different people,” he said, “but we have to do it through whole different mechanisms.”

In what may be a step in this direction, the Trump administration announced on Thursday that it would purchase 150 million rapid tests.

The most widely used diagnostic test for the new coronavirus, called a PCR test, provides a simple yes-no answer to the question of whether a patient is infected.

But similar PCR tests for other viruses do offer some sense of how contagious an infected patient may be: The results may include a rough estimate of the amount of virus in the patient’s body.

“We’ve been using one type of data for everything, and that is just plus or minus — that’s all,” Dr. Mina said. “We’re using that for clinical diagnostics, for public health, for policy decision-making.”

But yes-no isn’t good enough, he added. It’s the amount of virus that should dictate the infected patient’s next steps. “It’s really irresponsible, I think, to forgo the recognition that this is a quantitative issue,” Dr. Mina said.

The PCR test amplifies genetic matter from the virus in cycles; the fewer cycles required, the greater the amount of virus, or viral load, in the sample. The greater the viral load, the more likely the patient is to be contagious.

This number of amplification cycles needed to find the virus, called the cycle threshold, is never included in the results sent to doctors and coronavirus patients, although it could tell them how infectious the patients are.

In three sets of testing data that include cycle thresholds, compiled by officials in Massachusetts, New York and Nevada, up to 90 percent of people testing positive carried barely any virus, a review by The Times found.

On Thursday, the United States recorded 45,604 new coronavirus cases, according to a database maintained by The Times. If the rates of contagiousness in Massachusetts and New York were to apply nationwide, then perhaps only 4,500 of those people may actually need to isolate and submit to contact tracing.

One solution would be to adjust the cycle threshold used now to decide that a patient is infected. Most tests set the limit at 40, a few at 37. This means that you are positive for the coronavirus if the test process required up to 40 cycles, or 37, to detect the virus.

Tests with thresholds so high may detect not just live virus but also genetic fragments, leftovers from infection that pose no particular risk — akin to finding a hair in a room long after a person has left, Dr. Mina said.

Any test with a cycle threshold above 35 is too sensitive, agreed Juliet Morrison, a virologist at the University of California, Riverside. “I’m shocked that people would think that 40 could represent a positive,” she said.

A more reasonable cutoff would be 30 to 35, she added. Dr. Mina said he would set the figure at 30, or even less. Those changes would mean the amount of genetic material in a patient’s sample would have to be 100-fold to 1,000-fold that of the current standard for the test to return a positive result — at least, one worth acting on.

The Food and Drug Administration said in an emailed statement that it does not specify the cycle threshold ranges used to determine who is positive, and that “commercial manufacturers and laboratories set their own.”

The Centers for Disease Control and Prevention said it is examining the use of cycle threshold measures “for policy decisions.” The agency said it would need to collaborate with the F.D.A. and with device manufacturers to ensure the measures “can be used properly and with assurance that we know what they mean.”

The C.D.C.’s own calculations suggest that it is extremely difficult to detect any live virus in a sample above a threshold of 33 cycles. Officials at some state labs said the C.D.C. had not asked them to note threshold values or to share them with contact-tracing organizations.

For example, North Carolina’s state lab uses the Thermo Fisher coronavirus test, which automatically classifies results based on a cutoff of 37 cycles. A spokeswoman for the lab said testers did not have access to the precise numbers.

This amounts to an enormous missed opportunity to learn more about the disease, some experts said.

“It’s just kind of mind-blowing to me that people are not recording the C.T. values from all these tests — that they’re just returning a positive or a negative,” said Angela Rasmussen, a virologist at Columbia University in New York.

“It would be useful information to know if somebody’s positive, whether they have a high viral load or a low viral load,” she added.

Officials at the Wadsworth Center, New York’s state lab, have access to C.T. values from tests they have processed, and analyzed their numbers at The Times’s request. In July, the lab identified 872 positive tests, based on a threshold of 40 cycles.

With a cutoff of 35, about 43 percent of those tests would no longer qualify as positive. About 63 percent would no longer be judged positive if the cycles were limited to 30.

In Massachusetts, from 85 to 90 percent of people who tested positive in July with a cycle threshold of 40 would have been deemed negative if the threshold were 30 cycles, Dr. Mina said. “I would say that none of those people should be contact-traced, not one,” he said.

Other experts informed of these numbers were stunned.

“I’m really shocked that it could be that high — the proportion of people with high C.T. value results,” said Dr. Ashish Jha, director of the Harvard Global Health Institute. “Boy, does it really change the way we need to be thinking about testing.”

Dr. Jha said he had thought of the PCR test as a problem because it cannot scale to the volume, frequency or speed of tests needed. “But what I am realizing is that a really substantial part of the problem is that we’re not even testing the people who we need to be testing,” he said.

The number of people with positive results who aren’t infectious is particularly concerning, said Scott Becker, executive director of the Association of Public Health Laboratories. “That worries me a lot, just because it’s so high,” he said, adding that the organization intended to meet with Dr. Mina to discuss the issue.

The F.D.A. noted that people may have a low viral load when they are newly infected. A test with less sensitivity would miss these infections.

But that problem is easily solved, Dr. Mina said: “Test them again, six hours later or 15 hours later or whatever,” he said. A rapid test would find these patients quickly, even if it were less sensitive, because their viral loads would quickly rise.

PCR tests still have a role, he and other experts said. For example, their sensitivity is an asset when identifying newly infected people to enroll in clinical trials of drugs.

But with 20 percent or more of people testing positive for the virus in some parts of the country, Dr. Mina and other researchers are questioning the use of PCR tests as a frontline diagnostic tool.

People infected with the virus are most infectious from a day or two before symptoms appear till about five days after. But at the current testing rates, “you’re not going to be doing it frequently enough to have any chance of really capturing somebody in that window,” Dr. Mina added.

Highly sensitive PCR tests seemed like the best option for tracking the coronavirus at the start of the pandemic. But for the outbreaks raging now, he said, what’s needed are coronavirus tests that are fast, cheap and abundant enough to frequently test everyone who needs it — even if the tests are less sensitive.

“It might not catch every last one of the transmitting people, but it sure will catch the most transmissible people, including the superspreaders,” Dr. Mina said. “That alone would drive epidemics practically to zero.”

[1990C4S]

Originally Posted by cabmando

As I said in my first reply, the vaccine isn't a guarantee you don't get the virus. There is still a chance you can get it but you're supposed to get a less severe case if you do get it. Again, keep us posted and sorry for muddying up your thread with the argument about testing accuracy. I'll stop now.

This result will be fully investigated because it has some worrying issues, including variants, but also over-amplification leading to positives on vaccinated people.

I will report back, but it might take a while.

[cabmandone]

Originally Posted by 1990C4S

This result will be fully investigated because it has some worrying issues, including variants, but also over-amplification leading to positives on vaccinated people.

I will report back, but it might take a while.

Which vaccine did they get? The Pfizer and Moderna aren't supposed to create a positive because they don't use live virus so essentially they should be able to run the test for about as long as they want and not find live virus. J&J and AZ use live virus if I'm not mistaken... which I could be.

[cabmandone]

Originally Posted by brainz01

Java's on point as usual. For the lazy, here's an article from the toilet Paper of Record -- emphasis mine.

And BTW, different countries use various cycle thresholds for positivity which makes comparison of COVID statistics amongst nations with non-identical standards difficult.

NYT; Aug 29, 2020; Updated Jan 19, 2021
https://www.nytimes.com/2020/08/29/health/coronavirus-testing.html

Your Coronavirus Test Is Positive. Maybe It Shouldn’t Be.
By Apoorva Mandavilli

The usual diagnostic tests may simply be too sensitive and too slow to contain the spread of the virus.

Some of the nation’s leading public health experts are raising a new concern in the endless debate over coronavirus testing in the United States: The standard tests are diagnosing huge numbers of people who may be carrying relatively insignificant amounts of the virus.

Most of these people are not likely to be contagious, and identifying them may contribute to bottlenecks that prevent those who are contagious from being found in time. But researchers say the solution is not to test less, or to skip testing people without symptoms, as recently suggested by the Centers for Disease Control and Prevention.

Instead, new data underscore the need for more widespread use of rapid tests, even if they are less sensitive.

“The decision not to test asymptomatic people is just really backward,” said Dr. Michael Mina, an epidemiologist at the Harvard T.H. Chan School of Public Health, referring to the C.D.C. recommendation.

“In fact, we should be ramping up testing of all different people,” he said, “but we have to do it through whole different mechanisms.”

In what may be a step in this direction, the Trump administration announced on Thursday that it would purchase 150 million rapid tests.

The most widely used diagnostic test for the new coronavirus, called a PCR test, provides a simple yes-no answer to the question of whether a patient is infected.

But similar PCR tests for other viruses do offer some sense of how contagious an infected patient may be: The results may include a rough estimate of the amount of virus in the patient’s body.

“We’ve been using one type of data for everything, and that is just plus or minus — that’s all,” Dr. Mina said. “We’re using that for clinical diagnostics, for public health, for policy decision-making.”

But yes-no isn’t good enough, he added. It’s the amount of virus that should dictate the infected patient’s next steps. “It’s really irresponsible, I think, to forgo the recognition that this is a quantitative issue,” Dr. Mina said.

The PCR test amplifies genetic matter from the virus in cycles; the fewer cycles required, the greater the amount of virus, or viral load, in the sample. The greater the viral load, the more likely the patient is to be contagious.

This number of amplification cycles needed to find the virus, called the cycle threshold, is never included in the results sent to doctors and coronavirus patients, although it could tell them how infectious the patients are.

In three sets of testing data that include cycle thresholds, compiled by officials in Massachusetts, New York and Nevada, up to 90 percent of people testing positive carried barely any virus, a review by The Times found.

On Thursday, the United States recorded 45,604 new coronavirus cases, according to a database maintained by The Times. If the rates of contagiousness in Massachusetts and New York were to apply nationwide, then perhaps only 4,500 of those people may actually need to isolate and submit to contact tracing.

One solution would be to adjust the cycle threshold used now to decide that a patient is infected. Most tests set the limit at 40, a few at 37. This means that you are positive for the coronavirus if the test process required up to 40 cycles, or 37, to detect the virus.

Tests with thresholds so high may detect not just live virus but also genetic fragments, leftovers from infection that pose no particular risk — akin to finding a hair in a room long after a person has left, Dr. Mina said.

Any test with a cycle threshold above 35 is too sensitive, agreed Juliet Morrison, a virologist at the University of California, Riverside. “I’m shocked that people would think that 40 could represent a positive,” she said.

A more reasonable cutoff would be 30 to 35, she added. Dr. Mina said he would set the figure at 30, or even less. Those changes would mean the amount of genetic material in a patient’s sample would have to be 100-fold to 1,000-fold that of the current standard for the test to return a positive result — at least, one worth acting on.

The Food and Drug Administration said in an emailed statement that it does not specify the cycle threshold ranges used to determine who is positive, and that “commercial manufacturers and laboratories set their own.”

The Centers for Disease Control and Prevention said it is examining the use of cycle threshold measures “for policy decisions.” The agency said it would need to collaborate with the F.D.A. and with device manufacturers to ensure the measures “can be used properly and with assurance that we know what they mean.”

The C.D.C.’s own calculations suggest that it is extremely difficult to detect any live virus in a sample above a threshold of 33 cycles. Officials at some state labs said the C.D.C. had not asked them to note threshold values or to share them with contact-tracing organizations.

For example, North Carolina’s state lab uses the Thermo Fisher coronavirus test, which automatically classifies results based on a cutoff of 37 cycles. A spokeswoman for the lab said testers did not have access to the precise numbers.

This amounts to an enormous missed opportunity to learn more about the disease, some experts said.

“It’s just kind of mind-blowing to me that people are not recording the C.T. values from all these tests — that they’re just returning a positive or a negative,” said Angela Rasmussen, a virologist at Columbia University in New York.

“It would be useful information to know if somebody’s positive, whether they have a high viral load or a low viral load,” she added.

Officials at the Wadsworth Center, New York’s state lab, have access to C.T. values from tests they have processed, and analyzed their numbers at The Times’s request. In July, the lab identified 872 positive tests, based on a threshold of 40 cycles.

With a cutoff of 35, about 43 percent of those tests would no longer qualify as positive. About 63 percent would no longer be judged positive if the cycles were limited to 30.

In Massachusetts, from 85 to 90 percent of people who tested positive in July with a cycle threshold of 40 would have been deemed negative if the threshold were 30 cycles, Dr. Mina said. “I would say that none of those people should be contact-traced, not one,” he said.

Other experts informed of these numbers were stunned.

“I’m really shocked that it could be that high — the proportion of people with high C.T. value results,” said Dr. Ashish Jha, director of the Harvard Global Health Institute. “Boy, does it really change the way we need to be thinking about testing.”

Dr. Jha said he had thought of the PCR test as a problem because it cannot scale to the volume, frequency or speed of tests needed. “But what I am realizing is that a really substantial part of the problem is that we’re not even testing the people who we need to be testing,” he said.

The number of people with positive results who aren’t infectious is particularly concerning, said Scott Becker, executive director of the Association of Public Health Laboratories. “That worries me a lot, just because it’s so high,” he said, adding that the organization intended to meet with Dr. Mina to discuss the issue.

The F.D.A. noted that people may have a low viral load when they are newly infected. A test with less sensitivity would miss these infections.

But that problem is easily solved, Dr. Mina said: “Test them again, six hours later or 15 hours later or whatever,” he said. A rapid test would find these patients quickly, even if it were less sensitive, because their viral loads would quickly rise.

PCR tests still have a role, he and other experts said. For example, their sensitivity is an asset when identifying newly infected people to enroll in clinical trials of drugs.

But with 20 percent or more of people testing positive for the virus in some parts of the country, Dr. Mina and other researchers are questioning the use of PCR tests as a frontline diagnostic tool.

People infected with the virus are most infectious from a day or two before symptoms appear till about five days after. But at the current testing rates, “you’re not going to be doing it frequently enough to have any chance of really capturing somebody in that window,” Dr. Mina added.

Highly sensitive PCR tests seemed like the best option for tracking the coronavirus at the start of the pandemic. But for the outbreaks raging now, he said, what’s needed are coronavirus tests that are fast, cheap and abundant enough to frequently test everyone who needs it — even if the tests are less sensitive.

“It might not catch every last one of the transmitting people, but it sure will catch the most transmissible people, including the superspreaders,” Dr. Mina said. “That alone would drive epidemics practically to zero.”

If they're finding live virus at 40... they're infected right? Can they spread the virus if detected at 40? The article from MIT stated the lower the cycles the more viral load a person had. And for what it's worth, no he's not on point. It's absurd IMO to say "If we would have stopped at...." The accepted threshold seems to be 40. Is there an argument for lowering it? Maybe... but it is where it is and at 40 they were finding live virus which creates a positive test for covid.

[Tobra]

If they have a higher viral load, of course the test would take fewer cycles.

I would be surprised if any of them use live virus. PCR test should not be used the way we have been using it, or that is what the guy who developed it says.

[javadog]

You geniuses figure it out: