Abstract
Real-time RT-PCR is considered the gold standard confirmatory test for coronavirus disease 2019 (COVID-19). However, many scientists disagree, and it is essential to understand that several factors and variables can cause a false-negative test. In this context, cycle threshold (Ct) values are being utilized to diagnose or predict SARS-CoV-2 infection. This practice has a significant clinical utility as Ct values can be correlated with the viral load. In addition, Ct values have a strong correlation with multiple haematological and biochemical markers. However, it is essential to consider that Ct values might be affected by pre-analytic, analytic, and post-analytical variables such as collection technique, specimen type, sampling time, viral kinetics, transport and storage conditions, nucleic acid extraction, viral RNA load, primer designing, real-time PCR efficiency, and Ct value determination method. Therefore, understanding the interpretation of Ct values and other influential factors could play a crucial role in interpreting viral load and disease severity. In several clinical studies consisting of small or large sample sizes, several discrepancies exist regarding a significant positive correlation between the Ct value and disease severity in COVID-19. In this context, a revised review of the literature has been conducted to fill the knowledge gaps regarding the correlations between Ct values and severity/fatality rates of patients with COVID-19. Various databases such as PubMed, Science Direct, Medline, Scopus, and Google Scholar were searched up to April 2021 by using keywords including “RT-PCR or viral load”, “SARS-CoV-2 and RT-PCR”, “Ct value and viral load”, “Ct value or COVID-19”. Research articles were extracted and selected independently by the authors and included in the present review based on their relevance to the study. The current narrative review explores the correlation of Ct values with mortality, disease progression, severity, and infectivity. We also discuss the factors that can affect these values, such as collection technique, type of swab, sampling method, etc.
Highlights
The coronavirus disease 2019 (COVID-19) ongoing pandemic has caused catastrophe in the lives of millions of people worldwide
Given that rapid and accurate detection of SARS-CoV-2 is crucial in controlling the outbreak in the community and in hospitals, this review focuses on the concept of cycle threshold (Ct) values in COVID-19, and its relationship with disease severity, disease progression and infectivity
The RT-PCR technique has been exploited widely, and Ct values are considered as the indicators of viral load and may have a role in predicting the disease’s prognosis and severity
Summary
The coronavirus disease 2019 (COVID-19) ongoing pandemic has caused catastrophe in the lives of millions of people worldwide. Reports state that the peak SARS-CoV-2 load is seen during the first seven days of viral infection [19,20]. The SARS-CoV-2 real-time RT-PCR test reports as negative or positive in clinical practice, using a specific threshold for Ct values [28] (Figure 1). Figure methodology and thethe detection of of a positive sample in clinical practice, using a a specific threshold and Ct value. There are some ambiguities, such as whether it is best to use Ct values in predicting the level of infectivity and disease severity in patients infected with SARS-CoV-. Given that rapid and accurate detection of SARS-CoV-2 is crucial in controlling the outbreak in the community and in hospitals, this review focuses on the concept of Ct values in COVID-19, and its relationship with disease severity, disease progression and infectivity. We highlight factors affecting these values and present Ct values’ relationship with haematological and inflammatory biomarkers
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