Ruling out sars-cov-2 infeciton using exhaled breath analysis by electronic nose in a public health setting

Rationale: During the SARS-CoV-2 pandemic, rapid and accurate detection of infected individuals is crucial to control further spread. Electronic nose (eNose) technology is an emerging diagnostic tool for diagnosis and phenotyping of a wide variety of respiratory diseases. Hence, the accuracy of exhaled breath analysis by eNose was assessed for the discrimination between individuals with and without a SARS-CoV-2 infection. Methods: This was a prospective real-world study of individuals (≥18 years of age) presenting to a public testing center in Amsterdam, the Netherlands, August 2020 for SARS-CoV-2 detection. Baseline breath profiles were obtained using the SpiroNose [1,2], a cloud-connected eNose, after sampling of a combined throat and nasopharyngeal swab. A SARS-CoV-2 infection was defined as a positive molecular amplification test at baseline and/or ≤7 days after inclusion. Data-analysis involved advanced signal processing, ambient correction and statistics based on independent t-tests followed by linear discriminant and receiver operating characteristics (ROC) analysis [2]. The accuracy of the diagnostic model based on eNose sensor data was subsequently assessed in an independent validation set and in a replication set including newly presented individuals to the testing facilities in November 2020. Results: 1808 individuals with (n=68) and without (n=1760) SARS-CoV-2 infection were included, divided in a training (n=904) and validation (n=904) set. The eNose sensors were combined into a composite biomarker with an ROC-area under the curve (AUC) of 0.948 (95% Confidence Interval (CI):0.929-0.967) in the training set. These results were confirmed in the validation set (0.957;CI:0.942-0.971) and externally validated in a replication set with newly presented individuals (n=1089) with (n=151) and without (n=938) SARS-CoV-2 infection (0.935;CI:0.921-0.952) (Figure 1). A SARS-CoV-2 infection percentage score of 0.30 selected from the training set resulted in 100% sensitivity and 78% specificity in the validation set indicating that in 75% of individuals SARS-CoV-2 infection could have been reliably ruled out (0% false negative). In the replication set, the score resulted in 100% sensitivity and 80% specificity. Conclusions: Exhaled breath analysis by eNose can reliably distinguish between individuals with and without a SARS-CoV-2 infection in public health setting. This quick and non-invasive method can therefore be used as a screening instrument, eliminating the need for additional time-consuming, stressful, and expensive diagnostic tests. Thereby the number of required SARS-CoV-2 molecular amplification tests can be reduced by more than 70-75%. [1]de Vries R, Sterk PJ. J Allergy Clin Immunol. 2020 [2]de Vries R, Muller M, et al. Annals of Oncology 2019 .

Case-control study of patient characteristics, knowledge of the COVID-19 disease, risk behaviour and mental state in patients visiting an emergency room with COVID-19 symptoms in the Netherlands.

BACKGROUND: Coronavirus disease 2019 is a serious respiratory virus pandemic. Patient characteristics, knowledge of the COVID-19 disease, risk behaviour and mental state will differ between individuals. The primary aim of this study was to investigate these variables in patients visiting an emergency department in the Netherlands during the COVID-19 pandemic and to compare the "COVID-19 suspected" (positive and negative tested group) with the "COVID-19 not suspected" (control group) and to compare in the "COVID-19 suspected" group, the positive and negative tested patients. METHODS: Consecutive adult patients, visiting the emergency room at the Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands, were asked to fill out questionnaires on the abovementioned items on an iPad. The patients were either "COVID-19 suspected" (positive and negative tested group) or "COVID-19 not suspected" (control group). RESULTS: This study included a total of 159 patients, 33 (21%) tested positive, 85 (53%) negative and 41 (26%) were COVID-19 not suspected (control group). All patients in this study were generally aware of transmission risks and virulence and adhered to the non-pharmaceutical interventions. Working as a health care professional was correlated to a higher risk of SARS-Cov-2 infection (p- value 0.04). COVID-19 suspected patients had a significantly higher level of anxiety compared to COVID-19 not suspected patients (p-value < 0.001). The higher the anxiety, the more seriously hygiene measures were followed. The anxiety scores of the patients with (pulmonary) comorbidities were significantly higher than without comorbidities. CONCLUSION: This is one of the first (large) study that investigates and compares patient characteristics, knowledge, behaviour, illness perception, and mental state with respect to COVID-19 of patients visiting the emergency room, subdivided as being suspected of having COVID-19 (positive or negative tested) and a control group not suspected of having COVID-19. All patients in this study were generally aware of transmission risks and virulence and adhered to the non-pharmaceutical interventions. COVID-19 suspected patients and patients with (pulmonary) comorbidities were significantly more anxious. However, there is no mass hysteria regarding COVID-19. The higher the degree of fear, the more carefully hygiene measures were observed. Knowledge about the coping of the population during the COVID-19 pandemic is very important, certainly also in the perspective of a possible second outbreak of COVID-19.

Viral transmission in COVID-19: the role of the aerosol

Since there is no adequate treatment for COVID-19, prevention of the transmission of SARS-CoV2 is the best way to cope with the pandemic. National guidelines for non-pharmaceutical interventions focus mainly on the interference with viral transmission via droplets and surface by hygiene measures, limitation of human contact, and social distancing. There is growing evidence that a third route of transmission by aerosols - exhaled tiny particles with viable infectious virus that remain airborne for hours - may be relevant. This route may even be the predominant way of viral transmission in the case of so-called superspreading events. It implies the need for adequate ventilation at indoor spaces without recirculation of virus containing aerosols. Here, the use of face-masks might be of added value too. These measures appear to be especially pivotal during episodes of colder weather, when people spend significantly more time indoors.