RT-PCR: Cycle threshold value does not hold clinical relevance

A survey of 700 labs in the U.S. found that the Ct values could vary by up to 12 cycles for the same target gene across labs

The art of medicine is taught by the bedside. It involves detailed history-taking, followed by a physical examination which employs the senses of the physician. Humans, however, prefer concrete numbers to abstract skill and intuition. Unfortunately, most of these numbers do not have any clinical relevance. Yet, they continue to be used indiscriminately to drive irrational and often expensive treatments, including unnecessary hospitalisations. At present, the most often repeated number appears to be the cycle threshold value (Ct value) reported on an RT-PCR at the time of diagnosis.

An RT-PCR test detects genetic material in a sample (for COVID, the sample used is a swab from the throat and nose). The sample, after processing, is placed in an RT-PCR machine where the viral genetic material is amplified. So two copies of genetic material become four, four become eight in the next cycle and so on. There are fluorescent marker labels present in the mixture, which attach to the genetic material and release a fluorescent dye, which is measured by the machine as it happens (“real-time”). When the fluorescence crosses a certain threshold, the machine labels the sample as testing positive, and the number of cycles that the sample goes through before reaching this threshold is called the cycle threshold (or Ct value). It follows, therefore, that greater the quantum of genetic material (or virus) in the sample, fewer the cycles to reach the threshold of detection. For approximately every 3.3 rise in the Ct value, the quantum of starting genetic material is likely to be tenfold lower.