Cycle Threshold Values as Indication of Increasing SARS-CoV-2 New Variants, England, 2020-2022

Abstract

Early detection of increased infections or new variants of SARS-CoV-2 is critical for public health response. To determine whether cycle threshold (Ct) data from PCR tests for SARS-CoV-2 could serve as an early indicator of epidemic growth, we analyzed daily mean Ct values in England, UK, by gene target and used iterative sequential regression to detect break points in mean Ct values (and positive test counts). To monitor the epidemic in England, we continued those analyses in real time. During September 2020-January 2022, a total of 7,611,153 positive SARS-CoV-2 PCR test results with Ct data were reported. Spike (S) gene target (S+/S-)-specific mean Ct values decreased 6-29 days before positive test counts increased, and S-gene Ct values provided early indication of increasing new variants (Delta and Omicron). Our approach was beneficial in the context of the first waves of the COVID-19 pandemic and can be used to support future infectious disease monitoring.

Keywords: 2019 novel coronavirus disease; COVID-19; England; SARS-CoV-2; United Kingdom; coronavirus disease; polymerase chain reaction; quantitative real-time PCR; respiratory infections; severe acute respiratory syndrome coronavirus 2; viruses; zoonoses.

Figure 1

Weekly Taqpath reverse transcription quantitative PCR (27) gene detection (S+/S−) in SARS-CoV-2 infections, England, August 31, 2020–January 31, 2022. The chart excludes cycle threshold (Ct) values >30 for S− because when Ct >30, the S− may be caused by a sample of low quality or with low viral load rather than a reliable S− signal. Test results for which only 1 gene is detected are excluded. S, spike; S+, presence of S gene; S−, absence of S gene.

Figure 2

Daily mean Taqpath reverse transcription quantitative PCR (27) cycle threshold results by gene target profile (S+/S−) in SARS-CoV-2 infections, England, August 31, 2020–January 31, 2022. S+ indicates open reading frame ab1, nucleocapsid, and S detected; S− indicates open reading frame ab1 and nucleocapsid detected. Incidence, cases/100,000 population; S, spike; S+, presence of S gene; S−, absence of S gene.

Figure 3

Emergence of novel Alpha variant of SARS-CoV-2 in England, showing mean Ct values (A) and positive results for SARS-CoV-2 S tests (B) for September 3, 2020–January 31, 2021, according to a gamma model. Break points detected through iterative sequential regression (ISR) that indicate significant changes in mean Ct values and positive test counts are labeled. Blue line represents estimated S− mean Ct value and positive test counts by ISR. Blue lines at the base of the graph represent 95% CIs around the break points estimated by the ISR model. Ct, cycle threshold; S, spike; S+, presence of S gene; S−, absence of S gene.

Figure 4

Emergence of novel Delta variant of SARS CoV-2 in England, showing mean Ct values (A) and positive test counts for SARS CoV-2 S-gene–positive tests (B) for February 1, 2020, through November 30, 2021, according to a gamma model. Break points detected through iterative sequential regression (ISR) that indicate significant changes in mean Ct values and positive tests are labeled. Blue line represents estimated S− mean Ct value and positive test counts by ISR. Blue lines at the base of the graph represent 95% CIs around the breakpoints estimated by the ISR model. Ct, cycle threshold; S, spike; S+, presence of S gene; S−, absence of S gene.

Figure 5

Emergence of novel Omicron (BA.1) variant of SARS CoV-2 in England, showing mean Ct values (A) and positive test counts for SARS CoV-2 S–tests (B) from October 1, 2021, through January 31, 2022, according to a gamma model. Break points detected through iterative sequential regression (ISR) that indicate significant changes in mean Ct values and positive tests are labeled. Blue line represents estimated S− mean Ct value and positive test counts by ISR. Blue lines at the base of the graph represent 95% CIs around the break points estimated by the ISR model. Ct, cycle threshold; S, spike; S+, presence of S gene; S−, absence of S gene.