Active Infections, Amplification Cycles, Andrew Bostom, Anthony Fauci, Antigen Tests, Asymptomatic. Minimally Infectious, Brown University, CDC, Coronavirus, Covid-19, Cycle Threshold, DNA, Elon Musk, Eurosurveillence, False Positives, Molecular Tests, New York Times, PCR Tests, Portugal, Replication Cycles, RNA, SARS-CoV-2
We have a false-positive problem and even the New York Times noticed! The number of active COVID cases has been vastly exaggerated and still is, but there is more than one fix.
COVID PCR tests, which are designed to detect coronavirus RNA from a nasal swab, have a “specificity” of about 97%, and perhaps much less in the field. That means at least 3% of tests on uninfected subjects are falsely positive. But the total number of false positive tests can be as large or larger than the total number of true positives identified. Let’s say 3% of the tested population is truly infected. Then out of every 100 individuals tested, three individuals are actively infected and 97 are not. Yet about 3 of those 97 will test positive anyway! So in this example, for every true infection identified, the test also falsely flags an uninfected individual. The number of active infections is exaggerated by 100%.
But again, it’s suspected to be much worse than that. The specificity of PCR tests depends on the number of DNA replications, or amplification cycles, to which a test sample is subjected. That process is illustrated through three cycles in the graphic above. It’s generally thought that 20 – 30 cycles is sufficient to pick-up DNA from a live virus infection. If a sample is subjected to more than 30 cycles, the likelihood that the test will detect insignificant dead fragments of the virus is increased. More than 35 cycles prompts real concern about the test’s reliability. But in the U.S., PCR tests are regularly subjected to upwards of 35 and even 40-plus cycles of amplification. This means the number of active cases is exaggerated, perhaps by several times. If you don’t believe me, just ask the great Dr. Anthony Fauci:
“It’s very frustrating for the patients as well as for the physicians … somebody comes in, and they repeat their PCR, and it’s like [a] 37 cycle threshold, but you almost never can culture virus from a 37 threshold cycle. So, I think if somebody does come in with 37, 38, even 36, you got to say, you know, it’s just dead nucleotides, period.“
Remember, the purpose of the test is to find active infections, but the window during which most COVID infections are active is fairly narrow, only for 10 – 15 days after the onset of symptoms, and often less; those individuals are infectious to others only up to about 10 days, and most tests lag behind the onset of symptoms. In fact, infected but asymptomatic individuals — a third or more of all those truly infected at any given time — are minimally infectious, if at all. So the window over which the test should be sensitive is fairly narrow, and many active infections are not infectious at all.
PCR tests are subject to a variety of other criticisms. Many of those are discussed in this external peer-review report on an early 2020 publication favorable to the tests. In addition to the many practical shortfalls of the test, the authors of the original paper are cited for conflicts of interest. And the original paper was accepted within 24 hours of submission to the journal Eurosurveillance (what a name!), which should raise eyebrows to anyone familiar with a typical journal review process.
The most obvious implication of all the false positives is that the COVID case numbers are exaggerated. The media and even public health officials have been very slow to catch onto this fact. As a result, their reaction has sown a panic among the public that active case numbers are spiraling out of control. In addition, false positives lead directly to mis-attribution of death: the CDC changed it’s guidelines in early April for attributing death to COVID (and only for COVID, not other causes of death). This, along with the vast increase in testing, means that false positives have led to an exaggeration of COVID as a cause of death. Even worse, false positives absorb scarce medical resources, as patients diagnosed with COVID require a high level of staffing and precaution, and the staff often requires isolation themselves.
Many have heard that Elon Musk tested positive twice in one day, and tested negative twice in the same day! The uncomfortable reality of a faulty test was recently recognized by an Appeals Court in Portugal, and we may see more litigation of this kind. The Court ruled in favor of four German tourists who were quarantined all summer after one of them tested positive. The Court said:
“In view of current scientific evidence, this test shows itself to be unable to determine beyond reasonable doubt that such positivity corresponds, in fact, to the infection of a person by the SARS-CoV-2 virus.”
I don’t believe testing is a bad thing. The existence of diagnostic tests cannot be a bad thing. In fact, I have advocated for fast, cheap tests, even at the sacrifice of accuracy, so that individuals can test themselves at home repeatedly, if necessary. And fast, cheap tests exist, if only they would be approved by the FDA. Positive tests should always be followed-up immediately by additional testing, whether those are additional PCR tests, other molecular tests, or antigen tests. And as Brown University epidemiologist Andrew Bostom says, you should always ask for the cycle threshold used when you receive a positive result on a PCR test. If it’s above 30 and you feel okay, the test is probably not meaningful.
PCR tests are not ideal because repeat testing is time consuming and expensive, but PCR tests could be much better if the number of replication cycles was reduced to somewhere between 20 and 30. Like most flu and SARS viruses, COVID-19 is very dangerous to the aged and sick, so our resources should be focused on their safety. However, exaggerated case counts are a cause of unnecessary hysteria and cost, especially for a virus that is rather benign to most people.