Trends in SARS-CoV-2 Cycle Threshold Values in Bosnia and Herzegovina-A Retrospective Study

Abstract

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which led to the COVID-19 pandemic, has significantly impacted global public health. The proper diagnosis of SARS-CoV-2 infection is essential for the effective control and management of the disease. This study investigated the SARS-CoV-2 infection using RT-qPCR tests from laboratories in Bosnia and Herzegovina. We performed a retrospective study of demographic data and Ct values from 170,828 RT-qPCR tests from April 2020 to April 2023, representing 9.3% of total national testing. Samples were collected from 83,413 individuals across different age groups. Of all tests, 33.4% were positive for SARS-CoV-2, with Ct values and positivity rates varying across demographics and epidemic waves. The distribution was skewed towards older age groups, although lower positivity rates were observed in younger age groups. Ct values, indicative of viral load, ranged from 12.5 to 38. Lower Ct values correlated with higher positive case numbers, while higher Ct values signaled outbreak resolution. Additionally, Ct values decreased during epidemic waves but increased with the dominance of certain variants. Ct value-distribution has changed over time, particularly after the introduction of SARS-CoV-2 variants of interest/concern. Established Ct value trends might, therefore, be used as an early indicator and additional tool for informed decisions by public health authorities in SARS-CoV-2 and future prospective pandemics. Moreover, they should not be overlooked in future epidemiological events.

Keywords: Bosnia and Herzegovina; Ct values; SARS-CoV-2; decision-making tool; variants of concern.

Figure 2

The association of weekly median Ct values and the weekly positivity rates (period April 2020–April 2023). The observed trend in the slight but constant decrease in weekly median Ct values several weeks before the exponential growth of positive cases indicates the next epidemic wave. The shown increment size is every ten weeks covered by the study, starting with the first and ending with the last week. The number of the week and the corresponding year to which the displayed data refer are given in parentheses.

Figure 3

The distribution of cycle threshold (Ct) values per week (period April 2020–April 2023) is represented as a violinplot. The distribution of Ct values changed over time. The proportion of samples with low Ct increased with the proportion of positive tests and decreased when infection waned, indicating the end of the epidemic in 2023. The shown increment size is every ten weeks covered by the study, starting with the first and ending with the last week. The number of the week and the corresponding year to which the displayed data refer are given in parentheses.

Figure 4

Weekly distribution of tested individuals and positive cases from April 2020 to April 2023. The x–axis denotes the beginning of each epidemic year and the initiation of vaccination. The bars represent the total number of tests conducted (labelled “Tested”) and the number of individuals testing positive for SARS-CoV-2 infection (labelled “Positive”). Colored boxes below the x–axis denote the predominant SARS-CoV-2 variants identified in Bosnia and Herzegovina, based on data from the GISAID database.

Figure 5

The overall median Ct values are represented per age group. The highest median Ct values had the youngest age groups (newborns/toddlers and preschool children—0–5 years) and the oldest age groups (seniors—80+ years). While trends in median Ct values are evident, statistical analysis revealed no significant differences between age groups.

Figure 1

The investigated population with a number of tests performed in each age group represented per year. Prolonged positive individuals were recorded in all age groups. A total of 95.9% of individuals who tested positive had only one positive test result, 4.9% of individuals had between two and four consecutive positive test results (prolonged positive for less than 60 days), and 1.7% of individuals had between five and eight consecutive positive test results (prolonged positive for more than 60 days).