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Sang Young Kim, Jin-Pyo Lee, Woo-Ri Shin, In-Hwan Oh, ,
Published: 10 September 2022
Molecular & Cellular Toxicology, Volume 18, pp 443-455; https://doi.org/10.1007/s13273-022-00287-1

The publisher has not yet granted permission to display this abstract.
Published: 2 December 2021
by MDPI
Journal of Personalized Medicine, Volume 11; https://doi.org/10.3390/jpm11121274

Abstract:
(1) Introduction: According to recent studies, the ratio of C-reactive-protein to lymphocyte is more sensitive and specific than other biomarkers associated to systemic inflammatory processes. This study aimed to determine the prognostic value of CLR on COVID-19 severity and mortality at emergency department (ED) admission. (2) Methods: Between 1 March and 30 April 2020, we carried out a multicenter and retrospective study in six major hospitals of northeast France. The cohort was composed of patients hospitalized for a confirmed diagnosis of moderate to severe COVID-19. (3) Results: A total of 1,035 patients were included in this study. Factors associated with infection severity were the CLR (OR: 1.001, CI 95%: (1.000–1.002), p = 0.012), and the lymphocyte level (OR: 1.951, CI 95%: (1.024–3.717), p = 0.042). In multivariate analysis, the only biochemical factor significantly associated with mortality was lymphocyte rate (OR: 2.308, CI 95%: (1.286–4.141), p = 0.005). The best threshold of CLR to predict the severity of infection was 78.3 (sensitivity 79%; specificity 47%), and to predict mortality, was 159.5 (sensitivity 48%; specificity 70%). (4) Conclusion: The CLR at admission to the ED could be a helpful prognostic biomarker in the early screening and prediction of the severity and mortality associated with SARS-CoV-2 infection.
Published: 16 February 2021
Abstract:
Background: Rapid and accurate detection of SARS-CoV-2 infected individuals is crucial for taking timely measures and minimizing the risk of further SARS-CoV-2 spread. We aimed to assess the accuracy of exhaled breath analysis by electronic nose (eNose) for the discrimination between individuals with and without a SARS-CoV-2 infection.Methods: This was a prospective real-world study of individuals presenting to public test facility for SARS-CoV-2 detection by molecular amplification tests (TMA or RT-PCR). After sampling of a combined throat/nasopharyngeal swab, breath profiles were obtained using a cloud-connected eNose. Data-analysis involved advanced signal processing and statistics based on independent t-tests followed by linear discriminant and ROC analysis. Data from the training set were tested in a validation, a replication and an asymptomatic set.Findings: For the analysis 4510 individuals were available. In the training set (35 individuals with; 869 without SARS-CoV-2), the eNose sensors were combined into a composite biomarker with a ROC-AUC of 0.947 (CI:0.928-0.967). These results were confirmed in the validation set (0.957; CI:0.942-0.971, n=904) and externally validated in the replication set (0.937; CI:0.926-0.947, n=1948) and the asymptomatic set (0.909; CI:0.879-0.938, n=754). Selecting a cut-off value of 0.30 in the training set resulted in a sensitivity/specificity of 100/78, >99/84, 98/82% in the validation, replication and asymptomatic set, respectively.Interpretation: eNose represents a quick and non-invasive method to reliably rule out SARS-CoV-2 infection in public health test facilities and can be used as a screening test to define who needs an additional confirmation test.Funding: Ministry of Health, Welfare and SportResearch in context: Evidence before this study: Electronic nose technology is an emerging diagnostic tool for diagnosis and phenotyping of a wide variety of diseases, including inflammatory respiratory diseases, lung cancer, and infections.As of Feb 13, 2021, our search of PubMed using keywords “COVID-19” OR “SARS-CoV-2” AND “eNose” OR “electronic nose” OR “exhaled breath analysis” yielded 4 articles (1-4) that have assessed test characteristics of electronic nose to diagnose COVID-19. In these small studies the obtained signals using sensor-based technologies, two-dimensional gas chromatography and time-of-flight mass spectrometry, or proton transfer reaction time-of-flight mass spectrometry, provided adequate discrimination between patients with and without COVID-19.Added value of this study: We prospectively studied the accuracy of exhaled breath analysis by electronic nose (eNose) to diagnose or rule out a SARS-CoV-2 infection in individuals with and without symptoms presenting to a public test facility. In the training set with 904 individuals, the eNose sensors were combined into a composite biomarker with a ROC-AUC of 0.948. In three independent validation cohorts of 3606 individuals in total, eNose was able to reliably rule out SARS-CoV-2 infection in 70-75% of individuals, with a sensitivity ranging between 98-100%, and a specificity between 78-84%. No association was found between cycle thresholds values, as semi-quantitative measure of viral load, and eNose variables.Implications of all the available evidence: The available findings, including those from our study, support the use of eNose technology to distinguish between individuals with and without a SARS-CoV-2 infection with high accuracy. Exhaled breath analysis by eNose represents a quick and non-invasive method to reliably rule out a SARS-CoV-2 infection in public health test facilities. The results can be made available within seconds and can therefore be used as screening instrument. The eNose can reliably rule out a SARS-CoV-2 infection, eliminating the need for additional time-consuming, stressful, and expensive diagnostic tests in the majority of individuals.
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