The World Health Organization (WHO) recently published (14th Dec 2020, then updated 20th Jan 2021) a piece of advice for laboratories testing for SARS-CoV-2 using PCR. The advice boils down: new to PCR? Read the instructions and understand the purpose of testing. But of course, this lab-focussed advice has been taken by those with malicious intent, or with too little understanding of the topic, and blown it up into something else entirely wrong.
Target audience probably isn’t you
Look, the internet doesn’t necessarily always write just for you.
I’m sorry because this will come as a shock to some. It will disappoint others. A few will currently be pouring gasoline over their phone and lighting it on fire.
But as the WHO went to some extra lengths to make clear…
Target audience:Â laboratory professionals and users of IVDs.
From the people who wrote the document
That means for most of the planet – there’s nothing to see here because this is literally a document that says – “make sure you’ve read the manual”. It’s not even directed at expert pathology labs who already know what they are doing.
If you’re in the target audience – listen up
This was written because some of you, perhaps some doing high-throughput testing of human specimens for the first time ever – need to take some time to learn about what it is you’re trying to achieve here.
Basically, the document specifies that a PCR result is one part of a process of diagnosis. It’s to be taken in context. I feel like I may have said this 2,765 times before:
Most PCR assays are indicated as an aid for diagnosis, therefore, health care providers must consider any result in combination with timing of sampling, specimen type, assay specifics, clinical observations, patient history, confirmed status of any contacts, and epidemiological information..
From [1], bolding by me.
If you don’t use or run PCR in a pathology laboratory setting….
…you might need to go delete that tweet or post because you could be very wrong in your interpretation of this notice from the WHO.
Some certainly have posted material that was unsupported or wrong – and it was pounced upon by those among the angry anti-PCR (and anti-other things) cult.
Some examples
The misunderstanding below is around the WHO’s comment not to mess with the threshold for determining the threshold cycle (CT), if that contravenes the real-time RT-PCR test kit’s instructions for use (IFU) and you have no experience with doing so.
I have no idea how that was misinterpreted into becoming about changing the number of cycles used the RT-rPCR though. This bold but wrong statement was quickly retweeted (now deleted thankfully) and spread far and wide (the account has 330,768 followers and a television audience).
When a topic is so far removed from your area of expertise, it can be best to make doubly sure that you choose your words carefully. Your influence matters.
Another tweeter seems to be revelling in the WHO notice saying something more than it does as well, enthusiastically claiming they were right all along about their (actually quite wrong) claims of PCR test generating false positives. Sadly for them, the WHO notice provides no such support.
In the example below, the tweeter seems to have fallen into the same trap of misunderstanding, misreading or not reading at all the WHO Information Notice. They seem to think it says that the cycle number could be reduced. The Notice doesn’t say this.
Also, even if you were to reduce the cycle number by 10 (from, for example, 45 to 35), for the sake of appeasement, the majority of positives would still be uncontroversially positive if we go by the UK testing data below.
In this headline, the writer seems to have added in something about PCR not identifying a case of COVID-19 and a second test being required according to the WHO Notice.
Context is really lacking here. The WHO Notice doesn’t state this as written and this will likely lead some who only read headlines to walk away with the wrong impression.
WHO guidance Diagnostic testing for SARS-CoV-2 states that careful interpretation of weak positive results is needed (1). 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.
Quote from the WHO Notice [1]
The Notice discusses weak positive results (late or high CTs) – not all positives. It goes on to say that if the test doesn’t fit with the patient’s health (I’d add contact and epidemiological history) status, a new sample should be collected and the test repeated. A lab may use the initial test or a different test (good labs are armed with tests that target more than one genetic region of SARS-CoV-2 or come from more than one commercial supplier).
I could go on with examples and showing you how they are flawed takes – for whatever reason(s) – but you probably get the picture now.
The WHO Notice was clear, basic and meant for those labs that need some mentorship in pathology testing.
References
- WHO Information Notice for IVD Users 2020/05
https://www.who.int/news/item/20-01-2021-who-information-notice-for-ivd-users-2020-05 - Coronavirus (COVID-19) Infection Survey, UK: 22 January 2021
https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/coronaviruscovid19infectionsurveypilot/22january2021 - WHO releases new tightened guidelines regarding the diagnostic criteria for COVID-19. PCR positive no longer means you have COVID-19. You need a second test to confirm you have the virus
https://worldnewsera.com/news/startups/who-releases-new-tightened-guidelines-regarding-the-diagnostic-criteria-for-covid-19-pcr-positive-no-longer-means-you-have-covid-19-you-need-a-second-test-to-confirm-you-have-the-virus-tech-news/
Thank you for this quick explanation. How do supposedly intelligent people misunderstand? (Supposed, because they achieved doctoral-level recognition of their skills and knowledge.) I keep pointing out that the number of tests per person is multiple – using the Queensland government website as my go-to. (https://www.qld.gov.au/health/conditions/health-alerts/coronavirus-covid-19/current-status/statistics) Last reporting cycle: persons tested 1,911, samples tested 5,187. So, 3-4 tests have been required on each person’s sample for the experts to be able to come to a comfortably probable interpretation of whether the person was positive/negative for active COVID-19 at the time the sample was taken. [Apologies for any incorrect terminology. I’m an economic historian, not an epidemiologist, etc.!]
There are also a number of test kits in use in the USA and elsewhere that DON’T give ct numbers as results. They are just black box pos/neg results. Too many people in NZ and Aus latch on to articles (justifiably, imo) critical of these tests, not realising that “the PCR test” is not the same everywhere. And that in NZ and Aus we are already doing, and have been for months, all the things the WHO have recently suggested as being best practice.
None in Australia and New Zealand. We are already doing all the things the WHO say. In the USA? Who can tell. We are lucky to have few enough positive test results that we can easily do “further investigations” on all of them, and sequence their genomes to boot. I suspect that in countries with very high rate of positive tests a) they will be using a lot of fast kits that are not quantitative and b) they will not have the time available to follow up on borderline tests where they are using quantitative ones.
“Freeze” It would be nice if he could answer your question. As a researcher, Ive found it extremely difficult to obtain clarity to any issue that has a political bent to it. This guy seems the most objective ive come across yet. Im hopeful he finds his way back here soon. It is important to understand if what we know today about Covid science, retroactively effects what little we knew back at the beginning…because Policies and guidelines are still being created or enforced based on studies done at the beginning.