The association between real-time reverse transcriptase polymerase chain reaction cycle threshold values, symptoms and disease severity among COVID-19 patients in the community: a retrospective cohort study

Abstract

Background

COVID-19 continues to spread throughout the world. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) is used to diagnose COVID-19, with its cycle threshold (Ct) value inversely related to the viral load. The association between Ct values and COVID-19 related outcomes has been studied in the hospital setting but less so in the community. We aimed to estimate the association between Ct values and the severity of community-diagnosed COVID-19 to provide evidence on the utility of Ct testing in this setting.

Methods

This was a retrospective cohort study based on data from Israel’s largest health organization. The study population included 34,658 individuals who tested positive for COVID-19 by RT-PCR and had available Ct values between June 1^st and December 21^st, 2020. Outcomes included COVID-19 related symptoms, hospitalization, severe disease, and death. Ct values were modelled both as discrete and continuous exposures.

Results

After adjusting for known risk factors for severe COVID-19, low Ct values were associated with symptomatic disease (odds ratio [OR]: 1.51; 95% confidence interval [CI]:1.21–1.84), hospitalization (OR: 1.27; 95%CI: 1.12–1.49), severe disease (OR: 1.80; 95%CI: 1.43–2.27), and death (OR: 1.64; 95%CI: 1.06–2.59). By modelling the exposure as continuous, we noticed a dose-response relationship, with the risk gradually rising with lower Ct values.

Conclusions

This study found a significant association between low Ct values and severe COVID-19 related outcomes, with a dose-response relationship. This suggests that Ct values could be helpful in identifying high-risk patients diagnosed in the community.

Keywords:

• COVID-19
• severe COVID-19
• RT-PCR
• cycle threshold
• community

Ethical approval

This study was approved by Clalit Health Services’ ethics committee. The study was exempt from requiring informed consent.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

MMA, SK and NB conceived and designed the study. MMA, YBS, TH and ND participated in data extraction and analysis. MMA, SK, ND and NB wrote the manuscript. All authors critically reviewed the manuscript. RB and NB supervised the study process.

Data availability statement

Due to data privacy regulations, the raw data of this study cannot be shared.