Diagnostic performance of eNose technology in COVID-19 patients after hospitalization.

BACKGROUND: Volatile organic compounds (VOCs) produced by human cells reflect metabolic and pathophysiological processes which can be detected with the use of electronic nose (eNose) technology. Analysis of exhaled breath may potentially play an important role in diagnosing COVID-19 and stratification of patients based on pulmonary function or chest CT. METHODS: Breath profiles of COVID-19 patients were collected with an eNose device (SpiroNose) 3 months after discharge from the Leiden University Medical Centre and matched with breath profiles from healthy individuals for analysis. Principal component analysis was performed with leave-one-out cross validation and visualised with receiver operating characteristics. COVID-19 patients were stratified in subgroups with a normal pulmonary diffusion capacity versus patients with an impaired pulmonary diffusion capacity (DLCOc < 80% of predicted) and in subgroups with a normal chest CT versus patients with COVID-19 related chest CT abnormalities. RESULTS: The breath profiles of 135 COVID-19 patients were analysed and matched with 174 healthy controls. The SpiroNose differentiated between COVID-19 after hospitalization and healthy controls with an AUC of 0.893 (95-CI, 0.851-0.934). There was no difference in VOCs patterns in subgroups of COVID-19 patients based on diffusion capacity or chest CT. CONCLUSIONS: COVID-19 patients have a breath profile distinguishable from healthy individuals shortly after hospitalization which can be detected using eNose technology. This may suggest ongoing inflammation or a common repair mechanism. The eNose could not differentiate between subgroups of COVID-19 patients based on pulmonary diffusion capacity or chest CT.

Virus-induced breath biomarkers: A new perspective to study the metabolic responses of COVID-19 vaccinees.

Coronavirus disease 2019 (COVID-19) vaccines can protect people from the infection; however, the action mechanism of vaccine-mediated metabolism remains unclear. Herein, we performed breath tests in COVID-19 vaccinees that revealed metabolic reprogramming induced by protective immune responses. In total, 204 breath samples were obtained from COVID-19 vaccinees and non-vaccinated controls, wherein numerous volatile organic compounds (VOCs) were detected by comprehensive two-dimensional gas chromatography and time-of-flight mass spectrometry system. Subsequently, 12 VOCs were selected as biomarkers to construct a signature panel using alveolar gradients and machine learning-based procedure. The signature panel could distinguish vaccinees from control group with a high prediction performance (AUC, 0.9953; accuracy, 94.42%). The metabolic pathways of these biomarkers indicated that the host-pathogen interactions enhanced enzymatic activity and microbial metabolism in the liver, lung, and gut, potentially constituting the dominant action mechanism of vaccine-driven metabolic regulation. Thus, our findings of this study highlight the potential of measuring exhaled VOCs as rapid, non-invasive biomarkers of viral infections. Furthermore, breathomics appears as an alternative for safety evaluation of biological agents and disease diagnosis.

Quantitatively Visualizing Airborne Disease Transmission Risks of Different Exhalation Activities through CO2 Imaging.

Aerosol transmission has played a leading role in COVID-19 pandemic. However, there is still a poor understanding about how it is transmitted. This work was designed to study the exhaled breath flow dynamics and transmission risks under different exhaling modes. Using an infrared photography device, exhaled flow characteristics of different breathing activities, such as deep breathing, dry coughing, and laughing, together with the roles of mouth and nose were characterized by imaging CO2 flow morphologies. Both mouth and nose played an important role in the disease transmission though in the downward direction for the nose. In contrast to the trajectory commonly modeled, the exhaled airflows appeared with turbulent entrainments and obvious irregular movements, particularly the exhalations involving mouth were directed horizontal and had a higher propagation capacity and transmission risk. While the cumulative risk was high for deep breathing, those transient ones from dry coughing, yawning, and laughing were also shown to be significant. Various protective measures including masks, canteen table shields, and wearable devices were visually demonstrated to be effective for altering the exhaled flow directions. This work is useful to understanding the risk of aerosol infection and guiding the formulation of its prevention and control strategies. Experimental data also provide important information for refining model boundary conditions.

Protocol of a randomised controlled trial to assess medical staff's inhalation exposure to infectious particles exhaled by patients during oesophagogastroduodenoscopy and the efficacy of surgical masks in this context.

BACKGROUND: Aerosol-generating procedures such as oesophagogastroduodenoscopy (OGD) result in infectious particles being exhaled by patients. This substantially increases the medical staff's risk of occupational exposure to pathogenic particles via airway inhalation and facial mucosal deposition. Infectious particles are regarded as a key route of transmission of SARS-CoV-2 and, thus, represents a major risk factor for medical staff during the ongoing COVID-19 pandemic. There is a need for quantitative evidence on medical staff's risk of multiroute exposure to infectious particles exhaled by patients during OGD to enable the development of practical, feasible and economical methods of risk-reduction for use in OGD and related procedures. This randomised controlled trial (RCT)-Personal protective EquiPment intervention TrIal for oesophagogastroDuodEnoscopy (PEPTIDE)-aims to establish a state-of-the-art protocol for quantifying the multiroute exposure of medical staff to infectious particles exhaled by patients during real OGD procedures. METHOD AND ANALYSIS: PEPTIDE will be a prospective, two-arm, RCT using quantitative methods and will be conducted at a tertiary hospital in China. It will enrol 130 participants (65 per group) aged over 18. The intervention will be an anthropomorphic model with realistic respiratory-related morphology and respiratory function that simulates a medical staff member. This model will be used either without or with a surgical mask, depending on the group allocation of a participant, and will be placed beside the participants as they undergo an OGD procedure. The primary outcome will be the anthropomorphic model's airway dosage of the participants' exhaled infectious particles with or without a surgical mask, and the secondary outcome will be the anthropomorphic model's non-surgical mask-covered facial mucosa dosage of the participants' exhaled infectious particles. Analyses will be performed in accordance with the type of data collected (categorical or quantitative data) using SPSS (V.26.0) and RStudio (V.1.3.959). ETHICS AND DISSEMINATION: Ethical approval for this RCT was obtained from the Ethics Committee of Peking Union Medical College Hospital (ZS-3377). All of the potential participants who agree to participate will provide their written informed consent before they are enrolled. The results will be disseminated through presentations at national and international conferences and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05321056.

Mask device as a new wearable sampler for breath analysis: what can we expect in the future?

Human exhaled breath is becoming an attractive clinical source as it is foreseen to enable noninvasive diagnosis of many diseases. Because mask devices can be used for efficiently filtering exhaled substances, mask-wearing has been required in the past few years in daily life since the unprecedented COVID-19 pandemic. In recent years, there is a new development of mask devices as new wearable breath samplers for collecting exhaled substances for disease diagnosis and biomarker discovery. This paper attempts to identify new trends in mask samplers for breath analysis. The couplings of mask samplers with different (bio)analytical approaches, including mass spectrometry (MS), polymerase chain reaction (PCR), sensor, and others for breath analysis, are summarized. The developments and applications of mask samplers in disease diagnosis and human health are reviewed. The limitations and future trends of mask samplers are also discussed.

Quantitative evaluation of precautions against the COVID-19 indoor transmission through human coughing.

In this work, we focus on the dispersion of COVID-19-laden droplets using the transient computational fluid dynamics (CFD) modeling and simulation of the coughing process of virus carriers in an enclosure room, aiming to set up the basic prototype of popular precautionary strategies, i.e., face mask, upward ventilation, protective screen, or any combination thereof, against the indoor transmission of COVID-19 and other highly contagious diseases in the future. A multi-component Eulerian-Lagrangian CFD particle-tracking model with user-defined functions is utilized under 8 cases to examine the characteristics of droplet dispersion concerning the mass and heat transfer, droplet evaporation, air buoyancy, air convection, air-droplet friction, and turbulent dispersion. The result shows that implementing upward ventilation is the most effective measure, followed by wearing face masks. Protective screens can restrict the movement of the coughing droplets (though it will not reduce viral load). However, applying protective screens arranged with lean can be counterproductive in preventing the spread of COVID-19 when it is inappropriately placed with ventilation. The soundest solution is the combination of the face mask and upward ventilation, which can reduce the indoor infectious concentration by nearly 99.95% compared with the baseline without any precautionary strategies. With the resumption of school and work in the post-epidemic era, this study would provide intelligence-enhancing advice for the masses and rule-makers to curb the pandemic.

Determination of global chemical patterns in exhaled breath for the discrimination of lung damage in postCOVID patients using olfactory technology.

The objective of this work was to evaluate the use of an electronic nose and chemometric analysis to discriminate global patterns of volatile organic compounds (VOCs) in breath of postCOVID syndrome patients with pulmonary sequelae. A cross-sectional study was performed in two groups, the group 1 were subjects recovered from COVID-19 without lung damage and the group 2 were subjects recovered from COVID-19 with impaired lung function. The VOCs analysis was executed using a Cyranose 320 electronic nose with 32 sensors, applying principal component analysis (PCA), Partial Least Square-Discriminant Analysis, random forest, canonical discriminant analysis (CAP) and the diagnostic power of the test was evaluated using the ROC (Receiver Operating Characteristic) curve. A total of 228 participants were obtained, for the postCOVID group there are 157 and 71 for the control group, the chemometric analysis results indicate in the PCA an 84% explanation of the variability between the groups, the PLS-DA indicates an observable separation between the groups and 10 sensors related to this separation, by random forest, a classification error was obtained for the control group of 0.090 and for the postCOVID group of 0.088 correct classification. The CAP model showed 83.8% of correct classification and the external validation of the model showed 80.1% of correct classification. Sensitivity and specificity reached 88.9% (73.9%-96.9%) and 96.9% (83.7%-99.9%) respectively. It is considered that this technology can be used to establish the starting point in the evaluation of lung damage in postCOVID patients with pulmonary sequelae.

Numerical study of transient indoor airflow and virus-laden droplet dispersion: Impact of interactive human movement.

Human movement affects indoor airflow and the airborne transmission of respiratory infectious diseases, which has attracted scholars. However, the interactive airflow between moving and stationary people has yet to be studied in detail. This study used the numerical method validated by experimental data to explore the transient indoor airflow and virus-laden droplet dispersion in scenes with interactive human movement. Human-shaped numerical models and the dynamic mesh method were adopted to realize human movement in scenes with different lateral distances (0.2-1.2 m) between a moving person and stationary (standing/sitting) persons. The interactive human movement obviously impacts other persons' respiratory airflow, and the lateral fusion ranged about 0.6 m. The interactive human movement strengthens the indoor airflow convection, and some exhaled virus-laden droplets were carried into wake flow and enhanced long-range airborne transmission. The impact of interactive human movement on sitting patients' exhalation airflow seems more evident than on standing patients. The impact might last over 2 min after movement stopped, and people in the affected area might be at a higher exposure. The results can provide a reference for epidemic control in indoor environments.

Advanced setup for safe breath sampling and patient monitoring under highly infectious conditions in the clinical environment.

Being the proximal matrix, breath offers immediate metabolic outlook of respiratory infections. However, high viral load in exhalations imposes higher transmission risk that needs improved methods for safe and repeatable analysis. Here, we have advanced the state-of-the-art methods for real-time and offline mass-spectrometry based analysis of exhaled volatile organic compounds (VOCs) under SARS-CoV-2 and/or similar respiratory conditions. To reduce infection risk, the general experimental setups for direct and offline breath sampling are modified. Certain mainstream and side-stream viral filters are examined for direct and lab-based applications. Confounders/contributions from filters and optimum operational conditions are assessed. We observed immediate effects of infection safety mandates on breath biomarker profiles. Main-stream filters induced physiological and analytical effects. Side-stream filters caused only systematic analytical effects. Observed substance specific effects partly depended on compound's origin and properties, sampling flow and respiratory rate. For offline samples, storage time, -conditions and -temperature were crucial. Our methods provided repeatable conditions for point-of-care and lab-based breath analysis with low risk of disease transmission. Besides breath VOCs profiling in spontaneously breathing subjects at the screening scenario of COVID-19/similar test centres, our methods and protocols are applicable for moderately/severely ill (even mechanically-ventilated) and highly contagious patients at the intensive care.

A glimpse in post-COVID pathophysiology: the role of exhaled breath condensate pH as an early marker of residual alveolar inflammation.

BACKGROUND: Residual alveolar inflammation seems to be paramount in post-COVID pathophysiology. Currently, we still lack a reliable marker to detect and track alveolar phlogosis in these patients. Exhaled Breath Condensate (EBC) pH has robust evidences highlighting its correlation with lung phlogosis in various diseases. We aim to define the reliability of alveolar and bronchial EBC pH in the assessment and in the follow up of post-COVID-related inflammation. RESEARCH DESIGN AND METHODS: We enrolled 10 patients previously hospitalized due to COVID-19 pneumonia. We performed a complete follow-up after 3 months and 6 months from discharge. Each visit included routine blood tests, arterial blood gas analysis, 6-minute walking test, spirometry, diffusing capacity and body plethysmography. Finally, bronchial and alveolar EBC were collected at the end of each visit. RESULTS: Alveolar EBC pH was significantly lower than bronchial EBC pH at T1, alveolar EBC pH tended to be more acid after 3 months from hospital discharge compared to the same sample 6 months later. Serum inflammatory biomarkers showed no significant differences from T1 to T2. Alveolar EBC pH was positively correlated with neutrophil-lymphocyte ratio. CONCLUSIONS: Collecting EBC pH could help to understand pathophysiologic mechanism as well as monitoring alveolar inflammation in the post-COVID syndrome.

Clinical studies of detecting COVID-19 from exhaled breath with electronic nose.

The COVID-19 pandemic has attracted numerous research studies because of its impact on society and the economy. The pandemic has led to progress in the development of diagnostic methods, utilizing the polymerase chain reaction (PCR) as the gold standard for coronavirus SARS-CoV-2 detection. Numerous tests can be used at home within 15 min or so but of with lower accuracy than PCR. There is still a need for point-of-care tests available for mass daily screening of large crowds in airports, schools, and stadiums. The same problem exists with fast and continuous monitoring of patients during their medical treatment. The rapid methods can use exhaled breath analysis which is non-invasive and delivers the result quite fast. Electronic nose can detect a cocktail of volatile organic com-pounds (VOCs) induced by virus infection and disturbed metabolism in the human body. In our exploratory studies, we present the results of COVID-19 detection in a local hospital by applying the developed electronic setup utilising commercial VOC gas sensors. We consider the technical problems noticed during the reported studies and affecting the detection results. We believe that our studies help to advance the proposed technique to limit the spread of COVID-19 and similar viral infections.

Finding the infectious dose for COVID-19 by applying an airborne-transmission model to superspreader events.

We probed the transmission of COVID-19 by applying an airborne transmission model to five well-documented case studies-a Washington state church choir, a Korean call center, a Korean exercise class, and two different Chinese bus trips. For all events the likely index patients were pre-symptomatic or mildly symptomatic, which is when infective patients are most likely to interact with large groups of people. Applying the model to those events yields results that suggest the following: (1) transmission was airborne; (2) superspreading events do not require an index patient with an unusually high viral load; (3) the viral loads for all of the index patients were of the same order of magnitude and consistent with experimentally measured values for patients at the onset of symptoms, even though viral loads across the population vary by a factor of >108. In particular we used a Wells-Riley exposure model to calculate q, the total average number of infectious quanta inhaled by a person at the event. Given the q value for each event, the simple airborne transmission model was used to determined Sq, the rate at which the index patient exhaled infectious quanta and N0, the characteristic number of COVID-19 virions needed to induce infection. Despite the uncertainties in the values of some parameters of the superspreading events, all five events yielded (N0∼300-2,000 virions), which is similar to published values for influenza. Finally, this work describes the conditions under which similar methods can provide actionable information on the transmission of other viruses.

Collection and detection of SARS-CoV-2 in exhaled breath using face mask.

Face masks are used to protect the wearer from harmful external air and to prevent transmission of viruses from air exhaled by potentially infected wearers to the surrounding people. In this study, we examined the potential utility of masks for collecting viruses contained in exhaled breath and detected the collected viruses via various molecular tests. Using KF94 masks, the inner electrostatic filter was selected for virus collection, and an RNA extraction protocol was developed for the face mask. Virus detection in worn mask samples was performed using PCR and rolling circle amplification (RCA) tests and four different target genes (N, E, RdRp, and ORF1ab genes). The present study confirmed that the mask sample tests showed positive SARS-CoV-2 results, similar to the PCR tests using nasopharyngeal swab samples. In addition, the quantity of nucleic acid collected in the masks linearly increased with wearing time. These results suggest that samples for SARS-CoV-2 tests can be collected in a noninvasive, quick, and easy method by simply submitting worn masks from subjects, which can significantly reduce the hassle of waiting at airports or public places and concerns about cross-infection. In addition, it is expected that miniaturization technology will integrate PCR assays on face masks in the near future, and mask-based self-diagnosis would play a significant role in resolving the pandemic situation.

A user preference analysis of commercial breath ketone sensors to inform the development of portable breath ketone sensors for diabetes management in young people.

BACKGROUND: Portable breath ketone sensors may help people with Type 1 Diabetes Mellitus (T1DM) avoid episodes of diabetic ketoacidosis; however, the design features preferred by users have not been studied. We aimed to elucidate breath sensor design preferences of young people with T1DM (age 12 to 16) and their parents to inform the development of a breath ketone sensor prototype that would best suit their diabetes management needs. RESEARCH DESIGNS AND METHODS: To elicit foundational experiences from which design preference ideas could be generated, two commercially available breath ketone sensors, designed for ketogenic diet monitoring, were explored over one week by ten young people with T1DM. Participants interacted with the breath ketone sensing devices, and undertook blood ketone testing, at least twice daily for five days to simulate use within a real life and ambulatory care setting. Semi-structured interviews were conducted post-testing with the ten young participants and their caregivers (n = 10) to elicit preferences related to breath sensor design and use, and to inform the co-design of a breath ketone sensor prototype for use in T1DM self-management. We triangulated our data collection with key informant interviews with two diabetes educators working in pediatric care about their perspectives related to young people using breath ketone sensors. RESULTS: Participants acknowledged the non-invasiveness of breath sensors as compared to blood testing. Affordability, reliability and accuracy were identified as prerequisites for breath ketone sensors used for diabetes management. Design features valued by young people included portability, ease of use, sustainability, readability and suitability for use in public. The time required to use breath sensors was similar to that for blood testing. The requirement to maintain a 10-second breath exhalation posed a challenge for users. Diabetes educators highlighted the ease of use of breath devices especially for young people who tended to under-test using blood ketone strips. CONCLUSIONS: Breath ketone sensors for diabetes management have potential that may facilitate ketone testing in young people. Our study affirms features for young people that drive usability of breath sensors among this population, and provides a model of user preference assessment.

Analytic modeling and risk assessment of aerial transmission of SARS-CoV-2 virus through vaping expirations in shared micro-environments.

It is well known that airborne transmission of COVID-19 in indoor spaces occurs through various respiratory activities: breathing, vocalizing, coughing, and sneezing. However, there is a complete lack of knowledge of its possible transmission through exhalations of e-cigarette aerosol (ECA), which is also a respiratory activity. E-cigarettes have become widely popular among smokers seeking a much safer way of nicotine consumption than smoking. Due to restrictive lockdown measures taken during the COVID-19 pandemic, many smokers and vapers (e-cigarette users) were confined to shared indoor spaces, making it necessary to assess the risk of SARS-CoV-2 virus aerial transmission through their exhalations. We summarize inferred knowledge of respiratory particles emission and transport through ECA, as well as a theoretical framework for explaining the visibility of exhaled ECA, which has safety implications and is absent in other respiratory activities (apart from smoking). We also summarize and briefly discuss the effects of new SARS-CoV-2 variants, vaccination rates, and environmental factors that may influence the spread of COVID-19. To estimate the risk of SARS-CoV-2 virus aerial transmission associated with vaping exhalations, we adapt a theoretical risk model that has been used to analyze the risks associated with other respiratory activities in shared indoor spaces. We consider home and restaurant scenarios, with natural and mechanical ventilation, with occupants wearing and not wearing face masks. We consider as "control case" or baseline risk scenario an indoor space (home and restaurant) where respiratory droplets and droplet nuclei are uniformly distributed and aerial contagion risk might originate exclusively from occupants exclusively rest breathing, assuming this to be the only (unavoidable) respiratory activity they all carry on. If an infected occupant uses an e-cigarette in a home or restaurant scenarios, bystanders not wearing face masks exposed to the resulting ECA expirations face a [Formula: see text] increase of risk of contagion with respect the control case. This relative added risk with respect to the control case becomes [Formula: see text] for high-intensity vaping, [Formula: see text], and over [Formula: see text] for speaking for various periods or coughing (all without vaping). Infectious emissions are significantly modified by mechanical ventilation, face mask usage, vaccination, and environmental factors, but given the lack of empiric evidence, we assume as a working hypothesis that all basic parameters of respiratory activities are equally (or roughly equally) affected by these factors. Hence, the relative risk percentages with respect to the control state should remain roughly the same under a wide range of varying conditions. By avoiding direct exposure to the visible exhaled vaping jet, wearers of commonly used face masks are well protected from respiratory droplets and droplet nuclei directly emitted by mask-less vapers. Compared to the control case of an already existing (unavoidable) risk from continuous breathing, vaping emissions in shared indoor spaces pose just a negligible additional risk of COVID-19 contagion. We consider that it is not necessary to take additional preventive measures beyond those already prescribed (1.5 m separation and wearing face masks) in order to protect bystanders from this contagion.

Pulmonary Procedures During the COVID-19 Pandemic: A Work Group Report of the AAAAI Asthma Diagnosis and Treatment (ADT) Interest Section.

The COVID-19 pandemic has placed increased demands on the ability to safely perform pulmonary procedures in keeping with Centers for Disease Control and Prevention (CDC), American Thoracic Society (ATS), and the Occupational Safety and Health Administration (OSHA) recommendations. Accordingly, the American Academy of Allergy, Asthma & Immunology (AAAAI) Asthma Diagnosis and Treatment convened this work group to offer guidance. The work group is composed of specialist practitioners from academic and both large and small practices. Individuals with special expertise were assigned sections on spirometry, fractional exhaled nitric oxide, nebulized treatments, and methacholine challenge. The work group met periodically to achieve consensus. This resulting document has recommendations for the allergy/asthma/immunology health care setting based on available evidence including reference documents from the CDC, ATS, and OSHA.