Association between RT-PCR Ct values and COVID-19 new daily cases: a multicenter cross-sectional study

Abstract

Proactive prediction of the epidemiologic dynamics of viral diseases and outbreaks of the type of COV-ID-19 has remained a difficult pursuit for scientists, public health researchers, and policymakers. It is unclear whether RT-PCR Cycle Threshold (Ct) values of COVID-19 -or any other virus -as indicator of viral load, could represent a possible predictor for underlying epidemiologic changes on a population level. The study objective is thus to investigate whether population-wide changes in SARS-CoV-2 RT-PCR Ct values over time are associated with the daily fraction of positive COVID-19 tests. In addition, this study analyses the factors that could influence RT-PCR Ct values. A retrospective cross-sectional study was conducted on 63,879 patients from May 4, 2020 to September 30, 2020, in all COVID-19 facilities in the Kingdom of Bahrain. Data collected included number of tests and newly diagnosed cases, as well as Ct values, age, sex nationality, and symptomatic status. Ct values were found to be negatively and very weakly correlated with the fraction of daily positive tests in SUMMARY the population r = -0.06 (CI 95%: -0.06; -0.05; p=0.001). The R-squared for the regression model (adjusting for age and number of daily tests) showed an accuracy of 45.3%. Ct Values showed an association with nationality (p=0.012). After the stratification, the association between Ct values and the fraction of daily positive cases was only maintained for the female sex and Bahraini-nationality. Symptomatic presentation was significantly associated with lower Ct values (higher viral loads). Ct values do not show any correlation with age (p=0.333) or sex (p=0.522). We report one of the first and largest studies to investigate the epidemiologic associations of Ct values with COVID-19. Although changes in Ct values showed a moderate association with daily cases, our results indicate that it may not be as predictive within a simple model. More population studies and models from global cohorts are necessary.

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

“…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 ].…”

“…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 ]. At least 30 different polymerase chain reaction (PCR) assays were included in the studies, but not all were described in sufficient detail to give a precise count, with two studies not recording the PCR assay used [ 25 , 26 ].…”

“…Real-time RT–PCR Ct values represent the number of amplification cycles required for the target gene to exceed a threshold level, with a low Ct value corresponding to a high pathogen load. Ct values are inversely related to viral load and can provide an indirect method for quantifying the copy number of sample viral ribonucleic acid (RNA) [ 3 ]. Several studies have demonstrated a link between lower Ct values and increased disease severity [ 4 – 6 ].…”

“…Symptomatic presentation of COVID-19 has been significantly associated with lower Ct values, meaning higher viral load and prolonged virus shedding, which may play a role in determining the transmissibility and contagiousness of disease [ 3 ]. Therefore, a possible link between Ct values and epidemiology trends needs to be explored.…”

Can the nucleic acid Ct value of discharged patients infected with SARS-CoV-2 Omicron variant be 35?——A retrospective study on fluctuation of nucleic acid Ct values in SNIEC mobile cabin hospital

“…The use of the Ct value has been incorporated into Chinese guidelines for its rapid, highvolume testing mode. Moreover, the Ct value has a certain correlation with the progression of COVID-19 (Rao et al, 2020;Abdulrahman et al, 2021). In 2020, a systematic review by Sonia N. Rao, which identified 11 studies on the COVID-19 Ct value, found a relationship between the Ct value and disease severity (Rao et al, 2020).…”