Q: What is a cycle threshold value and can it be used to assess for contagiousness?
A: SARS-CoV-2 RT-PCR tests amplify viral RNA in a cyclic fashion. When the amount of fluorescence generated by the reaction crosses a predetermined threshold, the instrument declares the test positive, and the number of cycles it takes to reach that threshold is called the cycle threshold value. The lower the value, the greater the amount of viral RNA present in the original sample and vice versa. This information has been helpful from an infection control standpoint as there is an indirect correlation between Ct values and viral culture positivity, which is a widespread indicator for contagiousness. A person whose test has a low Ct value suggests a high burden of virus in the sample and is more worrisome for contagiousness than a test with a high Ct value.
However, there are a number of caveats to this. First, a Ct value gives you the least amount of virus possibly present in a sample. A person may have more than what was collected in the specimen due to poor sampling, inefficient amplification or because they are early in infection. Furthermore, there are no standardized values for what constitutes ‘low,’ ‘medium’ or ‘high’ Ct values; therefore, it is possible that the cutoffs used may lead to misclassification of noncontagious patients.
The clinical use of Ct values is not approved by IDSA or the Association for Molecular Pathology because they are also subject to numerous sources of variation (IDSA & AMP, March 2021 [PDF]). These include systematic bias between PCR platforms and even within a single platform, variability across sampling sites such as the anterior nares versus the nasopharynx, and variability in the methods by which instruments set thresholds and detect changes in fluorescence. Thus, a Ct value of 23 obtained from a PCR platform in one lab is not comparable to Ct value of 23 obtained from instruments at another lab or even different instruments in the same lab. Consultation with a clinical microbiologist or infectious diseases physician is recommended prior to making clinical decisions using Ct values.