key: cord-0701443-8yyahc0x authors: Mishra, Baijayantimala; Ranjan, Jai; Purushotham, Prashanth; Saha, Swarnatrisha; Payal, Poesy; Kar, Punyatoya; Das, Sivasankar; Deshmukh, Vaishnavi title: High proportion of low cycle threshold value as an early indicator of COVID‐19 surge date: 2021-09-15 journal: J Med Virol DOI: 10.1002/jmv.27307 sha: 2beda2e3de91300ce22426ed2ac0c26d9bda0ae7 doc_id: 701443 cord_uid: 8yyahc0x Many countries in the world are experiencing a recent surge in COVID‐19 cases. This is mainly attributed to the emergence of new SARS‐CoV‐2 variants. Genome sequencing is the only means to detect the evolving virus mutants and emerging variants. Cycle threshold values have an inverse relationship with viral load and lower Ct values are also found to be associated with increased infectivity. In this study, we propose to use Ct values as an early indicator for upcoming COVID‐19 waves. A retrospective cross‐sectional study was carried out to analyze the Ct values of positive samples reported during the first wave and second wave (April 2020–May 2021). Median Ct values of confirmatory genes were taken into consideration for comparison. Ct values below 25, >25–30, and >30 were categorized as high, moderate, and low viral load respectively. Our study found a significantly higher proportion of positive samples with a low Ct value (<25) across age groups and gender during the second wave of the COVID‐19 pandemic. A higher proportion of positive samples with a low Ct value (high viral load) may act as an early indicator of an upcoming surge. lower Ct values are also found to be associated with increased infectivity. In this study, we propose to use Ct values as an early indicator for upcoming COVID-19 waves. A retrospective cross-sectional study was carried out to analyze the Ct values analyzed for normality using the Shapiro-Wilk test. If data was normal, an independent t-test was used to calculate the mean difference between the groups. Mann-Whitney U-test was used to compare medians between two groups in case of skewed data. p < 0.05 was considered statistically significant. The peak positivity was recorded during the month of September 2020 and May 2021 for the first and second waves, respectively ( Figure 1 ). As the number of cases varied widely across the months in both the waves, the data was represented as the median and interquartile range and 41.6% versus 20.4%, respectively (Table 1) . To explore the difference in Ct value gender-wise and in different age groups, we compared the Ct value in these groups. The cycle threshold values of males and females were found to be comparable in 2020 and 2021 ( Figure 3 ). However, when the median Ct value in both the genders was compared year-wise between 2020 and 2021 the difference was found to be significant (median Ct 29 vs. 23), as shown in Figure 3 . We tried to look for the Ct value difference across different age groups during both the waves and the Ct value difference in each age group during the first and second waves. The median Ct value difference during the first wave and the second wave in each age group was found to be significant ( Figure 4 ). concern by the World Health Organization and shown to be more infectious. 10, 11 Significantly high proportion of positive cases with high viral load (low Ct) may be an early indicator of the pandemic surge. The median Ct value has also been suggested as a useful marker for predicting a pandemic surge. 6 Zein et al. 12 lower Ct value is uniformly seen among both the groups during the second wave. Ct value depends on several variables such as type and quantity of biological material, target genes, normalization of RT-PCR assay, different RT-PCR kits, and RT-PCR instruments, and so on. Therefore, the use of Ct value in a clinical setup for individual patient management purposes has been criticized. 16 However, the use of Ct values across population or locality has been shown to be a useful indicator of COVID-19 dynamics in the community. Our study highlights the importance of Ct value analysis on a population or locality basis. The higher proportion of positive samples with a low Ct value (high viral load) may act as an early indicator of an upcoming surge. With the continuance of pandemics and the emergence of virus variants, it is imperative to keep track of the virus and its behavioral pattern so that timely preventive action can be taken. Real-time genomic surveillance has failed to a large extent to predict the upcoming pattern of the pandemic surge, particularly in resourcelimited countries and countries with a high population burden. Realtime PCR being the most widely used diagnostic test for COVID-19, the observation of the pattern of Ct value by microbiologists has the potential to act as a readily available tool to give a signal of the upcoming pandemic surge. Second wave of COVID-19 in India: dissection of the causes and lessons learnt Challenges of SARS-CoV-2 genomic surveillance in Africa To interpret the SARS-CoV-2 test, consider the cycle threshold value Viral RNA load as determined by cell culture as a management tool for discharge of SARS-CoV-2 patients from infectious disease wards A narrative systematic review of the clinical utility of cycle threshold values in the context Comparison of the proportion of weekly Ct values in the first and second waves of COVID-19. Ct, cycle threshold of COVID-19 Correlation of population SARS-CoV-2 cycle threshold values to local disease dynamics: exploratory observational study Comparison of reversetranscription polymerase chain reaction cycle threshold values from respiratory specimens in symptomatic and asymptomatic children with severe acute respiratory syndrome coronavirus 2 infection Correlation between 3790 quantitative polymerase chain reaction-positives samples and positive cell cultures, including 1941 severe acute respiratory syndrome coronavirus 2 isolates Estimating epidemiologic dynamics from cross-sectional viral load distributions Increased household transmission of COVID-19 cases associated with SARS-CoV-2 variant of concern B.1.617.2: a national case-control study Tracking SARS-CoV-2 variants Declining trend in the initial SARS-CoV-2 viral load during the pandemic: preliminary observations from Detroit, Michigan. medRxiv Comparison of upper respiratory viral load distributions in asymptomatic and symptomatic children diagnosed with SARS-CoV-2 infection in pediatric hospital testing programs Clinical course and molecular viral shedding among asymptomatic and symptomatic patients with SARS-CoV-2 infection in a community treatment center in the Republic of Korea Comparison of symptomatic and asymptomatic infections due to severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in San Francisco long-term care facilities Misinterpretation of viral load in COVID-19 clinical outcomes High proportion of low cycle threshold value as an early indicator of COVID-19 surge The authors declare that there are no conflict of interests.