A study shows that coronavirus test cycle threshold (Ct) values should not be used to assess the performance of coronavirus tests or to triage COVID-19 patients.
The study was published in the American Association for Clinical Chemistry’s (AACC) Clinical Chemistry journal, according to a news release from the association.
Ct values are generated as part of the molecular coronavirus testing process.
In recommendations for coronavirus test developers, the World Health Organization (WHO) proposes a Ct of 25 as the minimum level of virus that should be detected by point-of-care coronavirus tests. Some research has also suggested that Ct values could potentially identify patients who have high viral loads and are at increased risk for serious disease.
However, the Association for Molecular Pathology (AMP) issued a joint statement with the Infectious Diseases Society of America (IDSA) in April urging caution in the use of SARS-CoV-2 PCR cycle threshold (Ct) values for clinical decision-making. In July, AACC issued a similar public statement.
In an effort to fill this data gap, a team of researchers led by Jim Huggett, PhD, of the U.K. National Measurement Laboratory at LGC, set out to determine how the WHO’s suggested Ct cut-off of 25 impacts coronavirus test performance, the AACC said in summarizing the study’s results. To do this, the researchers analyzed the results of more than 6,000 patients who underwent coronavirus PCR testing at three clinical laboratories in the U.K., Belgium, and the Republic of Korea. For the purposes of this study, all PCR tests used were considered to have 100% clinical sensitivity (i.e., the ability to correctly identify patients with COVID-19 100% of the time).
However, when Huggett’s team interpreted the tests’ results using the WHO’s cut-off, the tests’ clinical sensitivity dropped, varying from approximately 16% to 90% depending on the patient cohort.
Further analysis of data from 732 additional laboratories found that an individual Ct value can correspond to widely differing viral loads depending on the lab. For example, in theory the Ct value range of 25-30 corresponds to 106 copies of SARS-CoV-2/mL. In reality, however, the researchers found that that Ct range can correspond to as many as 108 copies/mL to as few as 103 copies/mL, AACC said.