SARS-CoV-2 Cycle Threshold: A Metric That Matters (or Not)

Growing evidence suggests Ct marks severe COVID-19 illness, but with few quantitative assays, lack of standardization across tests, labs shy from routinely reporting this value.

The cycle threshold (Ct) in reverse transcription polymerase chain reaction (RT-PCR) SARS-CoV-2 tests is gaining currency as a potential marker for severe disease in patients with COVID-19 illness. Amid mounting evidence in the clinical literature, however, some in the laboratory community are urging caution about the utility of this metric, how and even if it should be reported.

Ct refers to the number of cycles needed to amplify viral RNA to reach a detectable level. Certain testing platforms reveal Ct, but labs generally don’t provide the Ct value when reporting test results. It’s unclear how Ct should be applied in clinical settings. No standardization for Ct values exists across RT-PCR platforms, making it difficult to compare results among different tests. Researchers in clinical studies also haven’t validated using Ct to guide management of COVID-19 cases.

Several studies, however, point to a telling link between this viral load marker and severity of disease.

One review published in July in Infectious Diseases and Therapy reported an association between lower Ct values and not only worsening disease but also progression to severe disease and complications. Examining data from 18 studies, the investigators found significant correlations between Ct values and severe disease or death, as well as Ct and the presence of biochemical and hematological markers.

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