The World Health Organization (WHO) has acknowledged that a widely used PCR test for COVID-19 is subject to false positives, an admission that calls into question the actual number of confirmed cases of the coronavirus.
In issuing its January 20 notice, the Geneva-based WHO confirmed suspicions that the overly sensitive tests were detecting virus fragments, creating an inflated figure of COVID-19 infections. WHO’s action targets the PCR (polymerase chain reaction) test for the detection of the SARS-CoV-2, the virus that causes COVID-19.
Aimed at laboratory professionals and not necessarily the general public, the notice requests users to follow the instructions for use when interpreting results for specimens tested using PCR methodology. WHO notes that in testing for COVID-19, there is a need for “careful interpretation of weak positive results.”
To get a result using the PCR, labs must run the specimen through a specific number of cycles, known as the cycle threshold (CT).
“The CT is inversely proportional to the patient’s viral load,” the notice states. “When test results do not correspond to the clinical presentation, a new specimen should be taken and retested using the same or different NAT (nucleic acid testing) technology.”
The Problem with Mass Testing
The notice reminds labs that the prevalence of the disease can affect the predictive value of test results.
“As disease decreases, the risk for false positives increases,” the notice states.
The notice also reminds labs that the PCR test is an “aid for diagnosis.” Health care providers must consider a wide range of factors such as when the test was given, the specimen type, the assay specifics, and other patient information such as clinical observations, patient history, contacts, and other epidemiological information.
Questions about the accuracy of PCR tests long predated WHO’s action. PCR testing depends on the number of cycles through which a sample is run. The more cycles, the more fragments of the virus the test is likely to detect. This yields a “positive” result that may not tell whether the patient is truly infected.
Sensitivity at the Cost of Specificity
The WHO’s notice on the unreliability of PCR testing is not surprising, says Erwin Haas, M.D., an infectious disease expert and policy advisor to The Heartland Institute, which co-publishes Health Care News.
“‘Sensitivity’ can be increased, but only at the cost of ‘specificity,’ which is the probability that the test will falsely label individuals who do not have the disease as contagious and sick,” said Haas. “These false positives feed the public health juggernaut by inflating the number of ‘cases’ that can be reported to keep the hustle going.”
That “public health juggernaut” is evident, says Jane Orient, M.D., executive director of the Association of American Physicians and Surgeons and policy advisor to The Heartland Institute.
“Unfortunately, this information does not seem to be well known as of yet, and labs may not report the cycle threshold. So many are frightened and unnecessarily quarantined,” said Orient.
Despite recent outbreaks of COVID-19 variants in the United Kingdom and South Africa, both of which are spreading to other countries, the United States is seeing a decline in new cases—for now. The New York Times reported on January 29 that 165,000 people tested positive in the last week of January, down from about 250,000 at the beginning of the year. It is not clear how WHO’s warnings of misleading results from PCR tests, the ongoing distribution of vaccines, and the possibility of the new variants spreading in the United States will affect future case counts.
Bonner R. Cohen, Ph.D., (bcohen@nationalcenter.org) is a senior fellow at the National Center for Public Policy Research.