Making a diagnosis used to be a well understood and practised procedure: take a history from someone presenting with symptoms, examine them and do some tests to arrive at an overall diagnosis. It requires substantial training and experience to put this into practice. William Osler, known as one of the founders of modern medicine, often directed his trainees to ‘listen to the patient, he/she is telling you the diagnosis’.
With Covid-19, however, clinical diagnosis is seemingly a secondary consideration in the face of mass testing. All you require is a positive PCR test; no symptoms, no signs, no other diagnostic proof. But our limited understanding of mass testing and PCR suggests this might not suffice.
Detection of viruses using Polymerase Chain Reaction (PCR) is helpful so long as its accuracy can be understood: it offers the capacity to detect RNA in minute quantities, but whether that RNA represents infectious virus is another matter. RT-PCR uses enzymes called reverse transcriptase to change a specific piece of genetic material called RNA into a matching piece of genetic DNA. The test then amplifies this DNA exponentially; millions of copies of DNA can be made from a single viral RNA strand.
A fluorescent signal is attached to the DNA copies, and when the fluorescent signal reaches a certain threshold, the test is deemed positive. The number of cycles required before the fluorescence threshold is reached gives an estimate of how much virus is present in the sample. This measure is called the cycle threshold (Ct). The higher the cycle number, the less RNA there is in the sample; the lower the level, the greater the amount in the initial sample.
In a recent BMJ rapid response, doctors in Wales set out these problems when using the PCR test when there is low viral circulation in the population.
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