SARS-CoV-2 PCR cycle threshold at hospital admission associated with patient mortality

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cycle threshold (Ct) has been suggested as an approximate measure of initial viral burden. The utility of cycle threshold, at admission, as a predictor of disease severity 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). In-hospital mortality significantly differed (p<0.05) by Ct quartile. After adjusting for age, gender, BMI, hypertension and diabetes, increased cycle threshold was associated with decreased odds of in-hospital mortality (0.91, CI 0.89–0.94, p<0.001). Compared to the 4 th Quartile, patients with Ct values in the 1st Quartile (Ct <22.9) and 2nd Quartile (Ct 23.0–27.3) had an adjusted odds ratio of in-hospital mortality of 3.8 and 2.6 respectively (p<0.001). The discriminative ability of Ct to predict inpatient mortality was found to be limited, possessing an area under the curve (AUC) of 0.68 (CI 0.63–0.71).

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.

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  1. SciScore for 10.1101/2020.09.16.20195941: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study was approved by the Albert Einstein College of Medicine Institutional Review Board.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.


    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    While our study included a large and diverse cohort of patients due to its geographical location, some of the limitations included inability to analyze significance of race/ethnicity due to missing data from the medical records. This study could not explore viral load in non-hospitalized patients, and mild or asymptomatic patients were not initially swabbed due to hospital policy. Ct-based risk stratification or interpretation is also limited by the absence of absolute or constant Ct cut-off values. The Ct value ranges can vary widely by platform and are impacted by amplicon length, target region, PCR cycling protocols, and other reaction conditions which alter the overall PCR efficiency even when the same target gene is amplified.(4) Adopting the Ct value for clinical judgement is limited by the scope of error due to multiple factors including interpretation by the examiner.(4) Additionally, since testing is primarily upon nasopharyngeal swabs there is much greater variability from one collection to another in addition to variability between patient disease states.(4) Therefore, even with our promising results, the clinical applications of our findings would require further investigation to determine the ultimate value of Ct interpretation.

    Results from TrialIdentifier: No clinical trial numbers were referenced.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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