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

Stijn P. Andeweg, Jan van de Kassteele, Xiaorui Wang, Noortje van Maarseveen, Boris Vlaemynck, Sanne Bos, Harry Vennema, Lance Presser, Juan Juan Cai, Mirjam J. Knol, Dirk Eggink*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article number107362
Number of pages7
JournalInternational Journal of Infectious Diseases
Volume153
DOIs
Publication statusPublished - Apr 2025

Bibliographical note

Publisher Copyright:
© 2024 The Author(s)

Funding

This work was funded by the Ministry of Health, Welfare, and Sports (VWS). The Centre for Clinical Expertise at the National Institute for Public Health and the Environment (RIVM) assessed the research proposal following the specific conditions as stated in the law for medical research involving human subjects. The work described was exempted from further approval by the ethical research committee. Pathogen surveillance is a legal task of the RIVM and is carried out under the responsibility of the Dutch Minister of Health, Welfare, and Sports. The Public Health Act (Wet Publieke Gezondheid) provides that RIVM may receive pseudonymized data for this task without informed consent. The authors would like to thank all personnel at the 25 Public Health Services for data collection in the national surveillance database, the members of the RIVM genomic surveillance team, and the members of the RIVM COVID-19 surveillance and epidemiology team. Study design by SPA, MK, DE; Data collection by SPA, NvM, BV, MK, DE; Laboratory analyses by NvM, BV, SB. Data analysis and interpretation by SPA, JvdK, XW, HV, LP, JC, MK, DE; Writing by SPA, MK, DE. JC, MK, and DE were responsible for resources, supervision, project administration, and funding acquisition. All authors reviewed and approved the final version of the manuscript. Code for data processing, statistical analysis, figures, and tables can be found at GitHub (https://github.com/Stijn-A/SARS-CoV-2_Ct_value).

FundersFunder number
Ministerie van Volksgezondheid, Welzijn en Sport
Speech Pathology Australia
Rijksinstituut voor Volksgezondheid en Milieu
National Institute for Public Health and the Environment

    Keywords

    • Ct values
    • Molecular epidemiology
    • Prior infection
    • SARS-CoV-2
    • Vaccination
    • Viral load

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