Cycle Threshold Values


You may have heard discussion regarding using crossing threshold (Ct) values as a surrogate measure for the viral load of SARS-CoV-2. This has been a hot topic of discussion across the country. Recently the Infectious Disease Society of America and the Association for Molecular Pathology release a joint statement regarding the use of cycle threshold values for clinical decision-making

The take home message from the statement is that the Ct value should not be considered a quantitative measure of viral load. One should use caution in interpreting the relationship between Ct value and clinical decision making. 

Here are a few highlights from the statement:

  • there is a lack of definitive data to determine if the predictive values of Ct numbers can predict progression to severe COVID-19 disease, infer transmissibility, and differentiate active viral replication from prolonged shedding
  • there are multiple factors that can affect Ct values
    • adequacy of specimen collection
    • specimen type
    • dilution of sample in transport medium
    • specimen transport and storage
  • Not all qualitative PCR assay reliable correspond to RNA concentration
  • PCR assays are not consistent across different platforms

It is important to note the current FDA EUA assays are designed as qualitative assays, not quantitative assays. That is why you will not get a viral load with the result of positive or negative. Not all molecular diagnostic assays for the detection of SARS-CoV-2 will generate a Ct value. Even given these issues, there is an inverse relationship between the Ct value and the viral load. A low Ct value generally indicates a high viral load, while a high Ct value generally indicates a lower viral load. The biggest factors that distinguish a quantitative assay from a qualitative assay is the use of calibrates to generate a linear relationship between the Ct values. 

At MUSC, most of our Ct values come from the Cepheid Express assay and the Abbott assays. For the Abbott assay, the company uses the terminology Crossing Number (CN) as opposed to Ct. The two values are the same. If you are interested in the Ct value for a patient, please contact Infection Control. 

Up-to-date guidance from the CDC for reporting Ct values can be found on their FAQ page (updated 3/10/2021):https://www.cdc.gov/coronavirus/2019-ncov/lab/faqs.html#Interpreting-Results-of-Diagnostic-Tests 

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