Predicting outcomes of COVID-19 from admission biomarkers: a prospective UK cohort study
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Abstract
COVID-19 has an unpredictable clinical course, so prognostic biomarkers would be invaluable when triaging patients on admission to hospital. Many biomarkers have been suggested using large observational datasets but sample timing is crucial to ensure prognostic relevance. The DISCOVER study prospectively recruited patients with COVID-19 admitted to a UK hospital and analysed a panel of putative prognostic biomarkers on the admission blood sample to identify markers of poor outcome.
Methods
Consecutive patients admitted to hospital with proven or clinicoradiological suspected COVID-19 were consented. Admission bloods were extracted from the clinical laboratory. A panel of biomarkers (interleukin-6 (IL-6), soluble urokinase plasminogen activator receptor (suPAR), Krebs von den Lungen 6, troponin, ferritin, lactate dehydrogenase, B-type natriuretic peptide, procalcitonin) were performed in addition to routinely performed markers (C reactive protein (CRP), neutrophils, lymphocytes, neutrophil:lymphocyte ratio). Age, National Early Warning Score (NEWS2), CURB-65 and radiographic severity score on initial chest radiograph were included as comparators. All biomarkers were tested in logistic regression against a composite outcome of non-invasive ventilation, intensive care admission or death, with area under the curve (AUC) (figures calculated).
Results
187 patients had 28-day outcomes at the time of analysis. CRP (AUC: 0.69, 95% CI: 0.59 to 0.78), lymphocyte count (AUC: 0.62, 95% CI: 0.53 to 0.72) and other routine markers did not predict the primary outcome. IL-6 (AUC: 0.77, 0.65 to 0.88) and suPAR (AUC: 0.81, 0.72 to 0.88) showed some promise, but simple clinical features alone such as NEWS2 score (AUC: 0.70, 0.60 to 0.79) or age (AUC: 0.70, 0.62 to 0.77) performed nearly as well.
Discussion
Admission blood biomarkers have only moderate predictive value for predicting COVID-19 outcomes, while simple clinical features such as age and NEWS2 score outperform many biomarkers. IL-6 and suPAR had the best performance, and further studies should focus on the additive value of these biomarkers to routine care.
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SciScore for 10.1101/2020.06.25.20137935: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: The only exclusion criteria was an inability to consent. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations: The major limitation of this study is the limited sample size, leading to imprecise estimates of biomarker performance. A second limitation is the composite outcome of non-invasive ventilation, ITU admission and death which has been used in major interventional COVID-19 …
SciScore for 10.1101/2020.06.25.20137935: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: The only exclusion criteria was an inability to consent. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations: The major limitation of this study is the limited sample size, leading to imprecise estimates of biomarker performance. A second limitation is the composite outcome of non-invasive ventilation, ITU admission and death which has been used in major interventional COVID-19 trials. Although this is clinically useful and may aid differentiation of those who require specialist care, the provision and use of non-invasive ventilation is more clinician and hospital dependent and may be harder to extrapolate from. Finally, although around 80% of patients had blood available, 36 patients did not have stored blood, so only the routinely performed biomarkers (CRP, neutrophils, lymphocytes, neutrophil:lymphocyte ratio) are recorded for those patients. Another potential limitation is the composite outcome. Combining non-invasive ventilation, intensive care admission and death was a deliberate choice to reflect situations requiring high-level medical care, and is clinically useful, but is more subjective than other outcomes. However, our secondary analysis of intensive care admission and death was largely similar, supporting this approach.
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.
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