Development and validation of an early warning score to identify COVID-19 in the emergency department based on routine laboratory tests: a multicentre case-control study

Abstract

Objectives: Identifying patients with a possible SARS-CoV-2 infection in the emergency department (ED) is challenging. Symptoms differ, incidence rates vary and test capacity may be limited. As PCR-testing all ED patients is neither feasible nor effective in most centres, a rapid, objective, low-cost early warning score to triage ED patients for a possible infection is developed.

Design: Case-control study.

Setting: Secondary and tertiary hospitals in the Netherlands.

Participants: The study included patients presenting to the ED with venous blood sampling from July 2019 to July 2020 (n=10 417, 279 SARS-CoV-2-positive). The temporal validation cohort covered the period from July 2020 to October 2021 (n=14 080, 1093 SARS-CoV-2-positive). The external validation cohort consisted of patients presenting to the ED of three hospitals in the Netherlands (n=12 061, 652 SARS-CoV-2-positive).

Primary outcome measures: The primary outcome was one or more positive SARS-CoV-2 PCR test results within 1 day prior to or 1 week after ED presentation.

Results: The resulting 'CoLab-score' consists of 10 routine laboratory measurements and age. The score showed good discriminative ability (AUC: 0.930, 95% CI 0.909 to 0.945). The lowest CoLab-score had high sensitivity for COVID-19 (0.984, 95% CI 0.970 to 0.991; specificity: 0.411, 95% CI 0.285 to 0.520). Conversely, the highest score had high specificity (0.978, 95% CI 0.973 to 0.983; sensitivity: 0.608, 95% CI 0.522 to 0.685). The results were confirmed in temporal and external validation.

Conclusions: The CoLab-score is based on routine laboratory measurements and is available within 1 hour after presentation. Depending on the prevalence, COVID-19 may be safely ruled out in over one-third of ED presentations. Highly suspect cases can be identified regardless of presenting symptoms. The CoLab-score is continuous, in contrast to the binary outcome of lateral flow testing, and can guide PCR testing and triage ED patients.

Keywords: COVID-19; Clinical chemistry; Health informatics; accident & emergency medicine; statistics & research methods.

Figure 1

Inclusion flow of patients (pts) in the development (A) and temporal validation (B) data set. All patient admissions with routine venous blood sampling at the emergency department (ED) were included. For the development data set, completeness of the laboratory panel was assessed for all 28 laboratory tests; for the temporal validation data set this was only necessary for 10 laboratory tests. The major causes of missingness are described in the text. In the development data set, presentations with extreme values (>10 SD) were excluded. The same limits were applied to the temporal validation data set (see table 2 for limits).

Figure 2

Probability density plot of the CoLab linear predictor. The probability density plots for patients with COVID-19 (dark blue) and those without COVID-19 (light blue) are plotted against the linear predictor (see table 2). The CoLab-score cut-offs (−5.83, −4.02, −3.29, −2.34 and −1.64) are depicted with vertical dashed lines. The white-boxed numbers (between the cut-offs) represent the corresponding CoLab-score. Note that while the area under both curves is identical (since these are probability density functions), in absolute numbers the ‘negative or untested’ group is about 36 times larger than the PCR-positive group.

Figure 3

Inclusion flow of emergency department (ED) patients (pts) in three external centres. All ED presentations with routine venous blood sampling were included. Missingness of laboratory panels was assessed for the 11 variables in the CoLab-score (see table 2). Re-presentations after a positive PCR result or clinical COVID-19 registration were excluded as ‘previous COVID-19+’. Presentations with any laboratory result above the limits of the CoLab-score (see table 2) were excluded.