Saturday, June 19, 2021

97% of PCR positives aren’t false

A clip of a woman calling Bristol and Weston NHS Foundation Trust about coronavirus tests has been shared widely on social media.

In the clip, the caller claims that she has submitted a Freedom of Information request to the trust and found out that it runs its PCR tests with up to 45 cycles.

She says running PCR tests with more than 25 cycles means that most of the “positive” cases are false positives and the trust is “committing medical fraud and crimes against humanity.” 

This is not true. 

It is implausible that 97% of positives identified by PCR tests run at more than 25 cycles are false, as the caller claims. At higher cycles, PCR tests are more likely to detect people who have low levels of virus, which could indicate they are early or late in their infection. 

It doesn’t mean they are “false positives”. We’ve written more about cycle thresholds and the controversy surrounding them before.

What are PCR test cycles?

A PCR test works by first isolating and purifying any genetic material that you want to identify, and then repeatedly cooling and heating it in the presence of various substances to replicate it.

PCR tests are specific to the genetic material of interest—they don’t just replicate all the genetic material present. 

Some of the substances mixed with the sample produce fluorescence when they come into contact with the genetic material.

If the genetic material is present, more and more of it is replicated with each cycle, gradually increasing the fluorescence until it is detectable. 

The number of times the sample is heated and cooled before the fluorescence becomes detectable is called the cycle threshold. 

The fewer cycles required before fluorescence is observed, the greater the concentration of viral genetic material in the original sample, roughly speaking. 

Conversely, the more cycles that are required, the smaller the concentration of material in the original sample. 

Public Health England says that, typically, a maximum of 40 cycles are conducted when testing for SARS-CoV-2. Bristol and Weston Foundation Trust has said it runs 45 cycles on its PCR tests.

After all the cycles are done, if no fluorescence is detected, the sample is deemed to be negative. However, a positive PCR result after any number of cycles does indicate that the material of interest was present, if only in very small quantities.  

The caller’s claims

“I don’t know if you’re aware that Kary Mullis, the man who invented the PCR test said anything over 24 or 25 [cycles], you will find anything that you’re looking for”

Kary Mullis, the inventor of the PCR method, did say “with PCR, if you do it well, you can find almost anything in anybody,” though we can’t find an instance of him referring to a specific cycle number. 

But, regardless of what Kary Mullis did or didn’t say, it doesn’t mean that coronavirus PCR tests are frequently “detecting” false positives, in Bristol or anywhere else.

As mentioned, PCR tests are typically run with up to 40 cycles. During periods of low coronavirus prevalence, such as in summer 2020 or spring 2021, the PCR positivity rate in England has fallen below 1%. 

At those times, even if every single positive case was false, more than 99% of PCR tests were still returning negative results so it’s just not true that if you run PCR tests using more than 25 cycles “you will find anything that you’re looking for”. 

Nor are most Covid-19 cases found with an extremely high number of cycles. An academic study of the PCR tests conducted by the Office for National Statistics last year found that positive cases were detected after a median of 26.2 cycles. (So half were below this number and half were above.) 

“The PCR test, if you run it over a certain amount, if you run it over 25, you get a 97%, positive, false positive, which means you’re running yours on 45, which means 97% of your positives are false.”

It’s unclear whether the caller meant that:

  • 97% of all positives detected by PCR tests which are run with a maximum of 25 cycles or more (i.e. all PCR tests) are false (regardless of whichever cycle number the positive was detected), or 
  • 97% of positives detected after at least 25 cycles are false.

If she means that 97% of all PCR positives are false, this is demonstrably untrue. 

If 97% of all positives are false, then of the 3,834,387 positive cases so far detected in England by PCR, only 115,032 would have been “true” positives. Yet in England, more people have already died with Covid as a cause, in the opinion of their doctor.  

If she means that 97% of positives detected after at least 25 cycles are false, then there is no evidence to support that either. 

This claim may have originated from claims from an Irish GP called Dr Vincent Carroll who used similar figures when incorrectly describing the “false positive rate” (which is a different measure). When asked about the claim fact checker  thejournal.ie, Dr Carroll cited as evidence two scientific papers. But the authors of these papers say their research says no such thing. 

Both scientists contacted essentially said their papers showed that positives which were detectable only above 25 or 35 cycles indicated people who were not infectious.

But that doesn’t mean they are “false positives”. PCR tests do not diagnose illness or infection. They just detect whether the virus is in the sample or not. 

In theory, it is plausible that, at times of very low prevalence, the proportion of all positive results which are false positives could be very high. 

For example, if no-one at all had SARS-CoV-2, and one person tested positive, then the proportion of positives which were false would be 100%.

But that doesn’t mean the test is inaccurate, given it would have detected everyone else, correctly, as being negative. 

Besides, this clearly is not what happened during the pandemic, when many thousands of people in the UK have become ill and died. 

Also, it should be said that false negatives, where someone who genuinely has the virus tests negative, are also a concern when it comes to PCR tests.

This can be caused by, for example, people doing home tests not swabbing themselves correctly.

The ONS says: “Studies suggest that sensitivity may be somewhere between 85% and 98%,” meaning that the false negativity rate could be up to 15%.

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