Estimating the effect of COVID-19 vaccination and prior infection on cycle threshold values as a proxy of SARS-CoV-2 viral load

Objectives: SARS-CoV-2 viral load could be an important parameter for transmission potential. Here, we use quantitative reverse transcription-polymerase chain reaction cycle threshold (Ct) values as a proxy for viral load. We assess the effect of COVID-19 vaccination and prior infection status on Ct value while accounting for the virus variant. Methods: Using Dutch SARS-CoV-2 community testing data (n = 409,925 samples) from 8 March 2021 to 31 December 2022, separate univariable linear regressions were conducted for each explanatory variable, including age, sex, testing date, variant of infection, time since symptom onset, and testing laboratory. Subsequently, causal inference analysis assessed the impact of prior infection and vaccination status on Ct values, employing inverse propensity score weighting to adjust for confounders. Results: Our findings revealed a negative correlation between age and Ct values. Additionally, we observed modest differences in Ct values between different variants of infection, with lower Ct values (indicative of higher viral load) noted for Omicron variants compared to earlier variants. In addition, our results indicated an increase in Ct value (lower viral load) with prior infection. Conversely, the impact of vaccination was less pronounced. Conclusions: We observed an association between prior infection status and higher Ct values, suggesting a decrease in viral load, which could possibly indicate lower transmissibility.