Recently, some websites and internet users reported that the World Health Organization (WHO) ‘conceded that the number of COVID-19 positive cases was greatly overestimated’, and that the ‘new’ PCR test was invalid. The reports appear to stem from an announcement by the WTO advising laboratory technicians and scientists to carefully validate the PCR results and ensure that each test is carefully considered. Written in a fairly technical language – it was aimed at PCR scientists and experts in the field – it is understandable how much the wording was misinterpreted, but what is said in the announcement is not necessarily what has reached the public ears .
PCR testing
Let us first explain what a PCR test is. Polymerase Chain Reaction, or PCR, is simply a method of duplicating the genetic material in a sample to make more of it so that further tests can be performed. The test goes through different stages that are repeated up to 50 times, each of which exponentially duplicates the DNA / RNA – the less genetic material in the sample, the more cycles are needed to get the concentration high.
Scientists usually perform PCR if they have a sample of DNA or RNA and they search for specific genes in the sample, but the amount of genetic material is too small. Fumbling through a small DNA sample for a specific series without PCR would be like playing Where is Waldo with a very vague image – you need to make it clearer to find what you are looking for. PCR is our most powerful way of doing this.
But how does this relate to COVID-19? To detect the presence of SARS-CoV-2 in a patient, the test takes a swab from the throat, which will contain virus particles if the person is infected. A special form of PCR, called reverse transcriptase PCR (rt-PCR), is then used to amplify the amount of genetic material in the sample before it is tested for the presence of specific viral genes.
WHO confusion
PCR tests have been in place for almost a year to see if there is a COVID-19 infection, and this is our best method to understand the appearance of the virus. Recently, however, the WHO issued a report on how the test results should be carefully examined to ensure its accuracy, and some understood it as inaccurate.
This is the first of the two sections written by the WHO:
‘WHO guidance Diagnostic tests for SARS-CoV-2 require accurate interpretation of poorly positive results (1). The cycle threshold (Ct) required to detect virus is inversely proportional to the patient’s viral load. Where the test results do not correspond to the clinical presentation, a new sample must be taken and tested again with the same or different NAT technology. ”
This section simply asks that all positive test results that give a weak signal should be carefully examined to ensure that the result is truly positive and not false positive, and if the patient has symptoms of COVID-19, repeat the test to exactly to be sure. of the result. This procedure is likely to be written on many COVID-19 test sites as a reminder or an update of their official protocol, and it does not in any way indicate that the PCR test is inaccurate.
It also talks about the cycle threshold (Ct), which is the number of PCR cycles needed to make the signal strong enough to register. Some people claim that a large number of cycles will yield a positive result for anything – this is not true; more cycles are required if the genetic material concentration is very low, as in COVID-19 testing. More cycles cannot highlight the appearance of something that is not there.
The second part says this:
‘WHO reminds IVD users that the incidence of diseases changes the predictive value of test results; as the incidence of diseases decreases, the risk of false positives increases (2). This means that the probability that someone who has a positive result (SARS-CoV-2 detected) is actually infected with SARS-CoV-2 decreases as the incidence decreases, regardless of the alleged specificity.”
This explains why the probability of a person being positive for COVID-19 is lower as COVID-19 is less common in the population. Enrolling in an announcement is likely to be a reminder to investigate positive cases in areas with a low number of COVID-19 patients, and not a complete statement that PCR is inaccurate.
None of these sections “recognize that PCR testing at high gain rates alters the predictive value of the tests and results in a large number of false positive results”, as some have suggested. False positives in PCR tests are extremely uncommon, according to the UK government it currently ranges between 0.8 and 4.3 per cent. The vast majority of false positive results are due to analytical errors, which are not related to the PCR test or cycle number.
As for the rumor that the WHO has reduced the number of PCR cycles in its guidelines, it seems unfounded, and all that is recommended is that the cycle numbers be adjusted according to the test manufacturer’s instructions. The WHO suggests that in cases of a borderline test, in which the patient has a very low viral load, a second test should be performed.