Utility of the cycle threshold in anticipating the next phase of the coronavirus disease 2019 (COVID-19) pandemic

Systematic Review on the Correlation Between SARS-CoV-2 Real-Time PCR Cycle Threshold Values and Epidemiological Trends

“…The second pandemic wave had a unprecedented rapid surge of cases Penney et al. [ 17 ] 2022 USA To examine the association between Ct values from patients in a tertiary care ER department with the weekly state hospitalizations to evaluate the utility of using Ct values to estimate epidemiological trends and anticipate the next phase of the pandemic Retrospective Single unit Local There was a significant inverse correlation between median weekly Ct values and weekly incident hospitalizations for SARS-CoV-2 infections in Massachusetts Phillips et al. [ 13 ] 2022 USA To determine if temporal trends in SARS-CoV-2 Ct values from clinical testing were predictive of future cases to aid hospital-level surge planning Prospective Single unit Single unit Temporal trends in SARS-CoV-2 Ct values were predictive of future admission case numbers of COVID-19 at a specific hospital Stevens et al.…”

“…[ 25 ] Hospital and public 13,816 NR N, ORF, RdRp NR NR Delta variant (B.1.617) confirmed for second wave included in this study Positive samples reported during the first and second wave > 25, 25–30, and > 30 were categorized as high, moderate, and low viral load respectively NR No predictive modeling used in this study The study did not include correlation statistics but rather examined the Ct values over time of the two waves and found that the proportion of Ct values < 25 was significantly higher before the peak of the second wave of infections, which was associated with a more rapid surge of cases nationally Penney et al. [ 17 ] Hospital 342 Abbott M2000 SARS-CoV-2 assay, Abbott Park, IL, USA N, RdRp Nasopharyngeal NR NR Epidemiological trends and anticipating the next phase of the pandemic using median weekly incident hospitalizations due to SARS-CoV-2 infection in Massachusetts, obtained from the Massachusetts Department of Public Health NR NR No predictive modeling used in this study A strong inverse correlation (Pearson's correlation r = −0.76 ( P < 0.05)) was observed between the median Ct value and median weekly incident hospitalizations due to SARS-CoV-2 infection in Massachusetts, obtained from the Massachusetts Department of Public Health Phillips et al. [ 13 ] Hospital 2114 Lowest Ct value associated > 0 for E and N2 region for Xpert Xpress SARSCoV-2 assay OR a single Ct value that corresponds to the lowest Ct value > 0 for the Xpert Xpress SARS-CoV-2/Flu/RSV assay Xpert Xpress SARS-CoV-2 Assay, Cepheid, Sunnyvale CA, USA Xpert Xpress SARS-CoV-2/Flu/RSV assay, Cepheid, Sunnyvale CA, USA Both run on Infinity and XVI systems E, N2 Nasopharyngeal or anterior nasal NR NR Future changes in institutional COVID-19 cases NR 2 weeks When compared temporally, the average weekly Ct values for all tests performed negativ...…”

“…The studies were conducted in the USA [ 2 , 13 – 17 ], Europe [ 18 – 21 ], Africa [ 22 ], Australia [ 23 ], China [ 24 ], India [ 25 ], the Kingdom of Bahrain [ 3 ], and Lebanon [ 26 ]. RT–PCR Ct values were measured from public samples only (national or local), or from hospital and public samples in ten studies [ 3 , 14 , 18 – 25 ], and from hospital only or hospital and care home samples only in six studies [ 2 , 13 , 15 – 17 , 26 ]. Eleven studies included nasopharyngeal swabs [ 2 , 3 , 13 – 18 , 20 – 22 ], one study used nose and throat swabs [ 19 ], and four studies did not record the sample type [ 23 – 26 ].…”

“…Almost half the studies reported a time lag in the negative cross-correlation between Ct values and new daily cases, with seven studies reporting time lags between 1 and 3 weeks [ 2 , 3 , 13 , 15 , 18 , 20 , 26 ], and one study reporting a time lag of 33 days [ 14 ] (Table 2 ). Five studies looked at the correlation between Ct values and the stages of different epidemic waves of SARS-CoV-2 [ 15 – 17 , 21 , 23 ]. These studies found that as case numbers increased towards the peak of an epidemic wave there was an increase in viral loads as determined by low Ct values; towards the end of epidemic waves, there was also a higher proportion of patients with high Ct values, and therefore a decrease in viral load (Table 2 ).…”

The many clinical advantages of reporting the cycle threshold (Ct) value

“…Several lines of evidence now confirm that the Ct value is a significant predictor of emergence and progression of local SARS-CoV-2 outbreaks. This has been clearly demonstrated by Yin et al (2), who showed that the trends of Ct values predict epidemic trajectories in terms of future mean daily positive tests, as well as by Penney et al (3), who demonstrated that the trend of Ct values in SARS-CoV-2 positive samples significantly predicts incident COVID-19 hospitalizations. Besides these important epidemiological implications, mounting evidence reveals that monitoring routine Ct values of SARS-CoV-2 by means of accurate and standardized molecular assays may have substantial clinical implications.…”