SARS-CoV-2 PCR cycle threshold at hospital admission associated with Patient Mortality
Authors: Choudhuri Jui , Carter Jamal , Nelson Randin , Skalina Karin , Osterbur-Badhey Marika , Johnson Andrew , Goldstein Doctor , Paroder Monika , Szymanski James 
Published: September 2020

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cycle threshold (Ct) has been suggested as an approximate measure of initial viral burden. The relationship of initial Ct at hospitalization and patient mortality has not been thoroughly investigated.

Methods and findings

We conducted a retrospective study of SARS-CoV-2 positive, hospitalized patients from 3/26/2020 to 8/5/2020 who had SARS-CoV-2 Ct data within 48 hours of admission (n=1044). Only patients with complete survival data discharged (n=774) or died in hospital (n=270), were included in our analysis. Laboratory, demographic, and clinical data were extracted from electronic medical records. Multivariable logistic regression was applied to examine the relationship of patient mortality with Ct values while adjusting for established risk factors. Ct was analyzed as continuous variable and subdivided into quartiles to better illustrate its relationship with outcome. Cumulative incidence curves were created to assess whether there was a survival difference in the setting of the competing risks of death versus patient discharge.

Mean Ct at admission was higher for survivors (28.6, SD=5.8) compared to non-survivors (24.8, SD=6.0, P<0.001). Patients with lower Ct value on admission had higher odds ratio (0.91, CI 0.89-0.94, p<0.001) of in-hospital mortality after adjusting for age, gender, BMI, hypertension and diabetes. Patients with Ct values in 3rd Quartile (Ct 27.4-32.8) and 4th Quartile (Ct >32.9) had lower odds of in-hospital death (P<0.001). On comparing, Ct quartiles, mortality, BMI and GFR were significantly different (p<0.05) between the groups. The cumulative incidence of all-cause mortality and discharge was found to differ between Ct quartiles (Gray’s Test P<0.001).

Conclusion

SARS-CoV-2 Ct was found to be an independent predictor of patient mortality. However, further study is needed on how to best clinically utilize such information given the result variation due to specimen quality, phase of disease, and the limited discriminative ability of the test.

AUTHOR SUMMARY

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has effected the entire world, with approximately 23 million affected till date. Clinicians, researcher and scientists are making all efforts to identify ways of diagnosis, predicting outcome and treatment modalities. The polymerase chain reaction (rT-PCR) technology, is the standard test being used for the diagnosis and it gives an additional value known as “cycle threshold” (Ct), which is the number of PCR cycles required to cross the designated threshold and termed patient as positive for the infection. This Ct value is inverse of the viral load in the patient and has been studied as indicator of outcome of infection. In this study we have analyzed the Ct value as a predictor for mortality and compared it between different age and gender. We found the Ct value significantly different between those who survived and those who died due to the disease. However proper utilization of the Ct value needs further studies to be utilized in the clinical setting and guide decision making.