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.

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.

Biomarkers to identify Mycobacterium tuberculosis infection among borderline QuantiFERON results.

BACKGROUND: Screening for tuberculosis (TB) infection often includes QuantiFERON-TB Gold Plus (QFT) testing. Previous studies showed that two-thirds of patients with negative QFT results just below the cut-off, so-called borderline test results, nevertheless had other evidence of TB infection. This study aimed to identify a biomarker profile by which borderline QFT results due to TB infection can be distinguished from random test variation. METHODS: QFT supernatants of patients with a borderline (≥0.15 and <0.35 IU·mL-1), low-negative (<0.15 IU·mL-1) or positive (≥0.35 IU·mL-1) QFT result were collected in three hospitals. Bead-based multiplex assays were used to analyse 48 different cytokines, chemokines and growth factors. A prediction model was derived using LASSO regression and applied further to discriminate QFT-positive Mycobacterium tuberculosis-infected patients from borderline QFT patients and QFT-negative patients RESULTS: QFT samples of 195 patients were collected and analysed. Global testing revealed that the levels of 10 kDa interferon (IFN)-γ-induced protein (IP-10/CXCL10), monokine induced by IFN-γ (MIG/CXCL9) and interleukin-1 receptor antagonist in the antigen-stimulated tubes were each significantly higher in patients with a positive QFT result compared with low-negative QFT individuals (p<0.001). A prediction model based on IP-10 and MIG proved highly accurate in discriminating patients with a positive QFT (TB infection) from uninfected individuals with a low-negative QFT (sensitivity 1.00 (95% CI 0.79-1.00) and specificity 0.95 (95% CI 0.74-1.00)). This same model predicted TB infection in 68% of 87 patients with a borderline QFT result. CONCLUSIONS: This study was able to classify borderline QFT results as likely infection-related or random. These findings support additional laboratory testing for either IP-10 or MIG following a borderline QFT result for individuals at increased risk of reactivation TB.

Livestock-associated methicillin-resistant Staphylococcus aureus epidemiology, genetic diversity, and clinical characteristics in an urban region.

Objectives: While Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA), defined as CC398, is a well-known pathogen among those working with livestock, there are indications that LA-MRSA prevalence among the general population is increasing. However, the clinical impact in urban areas remains unknown. The aim of this study was to assess the genetic epidemiology and clinical characteristics of LA-MRSA in an urban area with a limited livestock population. Methods: In this retrospective study, we evaluated LA-MRSA strains that were collected between 2014 and 2018 from patients who received clinical care in a single urban area in Netherlands. Patient files were assessed for livestock exposure data, clinical findings, and contact tracing information. Next-generation sequencing (NGS) analysis in combination with wgMLST was conducted to assess genetic diversity and relatedness and to detect virulence and resistance genes. Results: LA-MRSA strains were cultured from 81 patients, comprising 12% of all the MRSA strains found in seven study laboratories between 2014 and 2018. No livestock link was found in 76% of patients (n = 61), and 28% of patients (n = 23) had an infection, mostly of the skin or soft tissue. Contact tracing had been initiated in 14 cases, leading to the identification of two hospital transmissions: a cluster of 9 cases and one of 2 cases. NGS data were available for 91% (n = 75) of the patients. wgMLST confirmed the clusters detected via contact tracing (n = 2) and identified 5 additional clusters without a known epidemiological link. Relevant resistance and virulence findings included the PVL virulence gene (3 isolates) and tetracycline resistance (79 isolates). Conclusion: LA-MRSA may cause a relevant burden of disease in urban areas. Surprisingly, most infections in the present study occurred in the absence of a livestock link, suggesting inter-human transmission. These findings and the presence of PVL and other immune evasive complex virulence genes warrant future surveillance and preventative measures.

Detection of methicillin-resistant Staphylococcus aureus in a low-prevalence setting by polymerase chain reaction with a selective enrichment broth.

The objective of this study was to evaluate the test characteristics of a modified BD GeneOhm methicillin-resistant Staphylococcus aureus (MRSA) assay on individual and pooled samples in a setting of low MRSA prevalence. The results of the polymerase chain reaction (PCR) assay were compared with culture results from a selective phenol red mannitol broth subcultured after 48 h. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) were calculated. For individual testing, 581 samples from 201 persons were collected; 18 (3.2%) were MRSA culture positive. Five hundred ten broths from 174 persons were combined in 106 pools after overnight incubation; 8 pools (7.5%) contained 1 or more MRSA culture-positive specimens. There were no inhibited PCR tests. The combined sensitivity of individual and pooled specimens was 92% (95% confidence interval [CI], 73-99%), the specificity was 98% (95% CI, 96-99%), and the PPV and NPV were 63% and 99.7%, respectively. Our modified procedure gives satisfactory results, and the pooling of broths may reduce costs.