Recently, some sites and Internet users have been reporting that the World Health Organization (WHO) has "admitted the number of COVID-19 positive cases is grossly overestimated", and that the "new" PCR test is invalid. The reports appear to stem from an announcement by the WHO advising lab technicians and testing scientists to carefully validate the PCR results, and to ensure that each test is carefully considered. Written in quite technical language – it was aimed at PCR scientists and experts in the field – it is understandable how many misconstrued the wording, but what is said in the announcement is not necessarily what has reached public ears.
Firstly, let's explain what a PCR test is. Polymerase Chain Reaction, or PCR, is simply a method for duplicating the genetic material in a sample to make more of it, so that further tests can be performed. The test cycles through different stages that are repeated up to 50 times, each one duplicating the DNA/RNA exponentially – the less genetic material in the sample, the more cycles needed to get it to a high enough concentration.
Scientists usually perform PCR when they have a sample of DNA or RNA and they are looking for specific genes within that sample but the amount of genetic material is too small. Rummaging through a tiny DNA sample for a specific sequence without PCR would be like trying to play Where’s Waldo with a really blurry image – you need to make it clearer to find what you’re looking for. PCR is our most powerful method 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 virus genes.
PCR tests have been in force to check for COVID-19 infection for almost a year now, and have been our best method for understanding the prevalence of the virus. However, recently the WHO released a report relating to how the test results should be carefully scrutinized to ensure its accuracy, and some have taken to understand this as the test being inaccurate.
This is the first of two passages written by the WHO:
“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.”
This passage simply calls for any positive test results that give a weak signal to be scrutinized carefully to ensure the result is a true positive and not a false positive, and if the patient has symptoms of COVID-19, repeat the test to be exactly sure of the result. Likely written as a reminder or an update to their official protocol, this procedure is already done in many COVID-19 testing locations and is by no means stating 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 high number of cycles will give a positive result for anything – this is not true, more cycles are needed when the genetic material concentration is very low, as it is in COVID-19 testing. More cycles cannot highlight the presence of something that isn’t there.
The second passage states this:
“WHO reminds IVD users that disease prevalence alters the predictive value of test results; as disease prevalence decreases, the risk of false positive increases (2). This means that the probability that a person who has a positive result (SARS-CoV-2 detected) is truly infected with SARS-CoV-2 decreases as prevalence decreases, irrespective of the claimed specificity.”
This explains that the likelihood a person is positive for COVID-19 is lower when COVID-19 is less common in the population. Writing this into an announcement is likely a reminder to scrutinize positive cases in areas with a low number of COVID-19 patients and not a blanket statement that PCR is inaccurate.
Neither of these passages "admits that PCR testing at high amplification rates alters the predictive value of the tests and results in a huge number of false positives" as some have suggested. False positives in PCR tests are extremely uncommon, with the number currently ranging from 0.8 percent to 4.3 percent according to the UK government. The vast majority of false positives occur as a result of analytical errors, having no relation to the PCR test or cycle number.
As for the rumor that the WHO has reduced the number of PCR cycles in its guidelines, this appears unfounded and all that is recommended is that cycle numbers are adjusted in keeping with test manufacturer 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 carried out.