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1.
J Allergy Clin Immunol Pract ; 10(6): 1474-1484, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1878213

ABSTRACT

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.


Subject(s)
Asthma , COVID-19 , Hypersensitivity , Asthma/diagnosis , Asthma/epidemiology , Asthma/therapy , Breath Tests/methods , Exhalation , Humans , Nitric Oxide , Pandemics/prevention & control , Spirometry
2.
JAMA ; 327(19): 1860, 2022 05 17.
Article in English | MEDLINE | ID: covidwho-1864226
3.
Nitric Oxide ; 124: 68-73, 2022 07 01.
Article in English | MEDLINE | ID: covidwho-1851878

ABSTRACT

OBJECTIVE: To assess the feasibility of Fractional exhaled Nitric Oxide (FeNO) as a simple, non-invasive, cost-effective and portable biomarker and decision support tool for risk stratification of COVID-19 patients. METHODS: We conducted a single-center prospective cohort study of COVID-19 patients whose FeNO levels were measured upon ward admission by the Vivatmo-me handheld device. Demographics, COVID-19 symptoms, and relevant hospitalization details were retrieved from the hospital databases. The patients were divided into those discharged to recover at home and those who died during hospitalization or required admission to an intensive care unit, internal medicine ward, or dedicated facility (severe outcomes group). RESULTS: Fifty-six patients were enrolled. The only significant demographic difference between the severe outcomes patients (n = 14) and the home discharge patients (n = 42) was age (64.21 ± 13.97 vs. 53.98 ± 15.57 years, respectively, P = .04). The admission FeNO measurement was significantly lower in the former group compared with the latter group (15.86 ± 14.74 vs. 25.77 ± 13.79, parts per billion [PPB], respectively, P = .008). Time to severe outcome among patients with FeNO measurements ≤11.8 PPB was significantly shorter compared with patients whose FeNO measured >11.8 PPB (19.25 ± 2.96 vs. 24.41 ± 1.09 days, respectively, 95% confidence interval [CI] 1.06 to 4.25). An admission FeNO ≤11.8 PPB was a significant risk factor for severe outcomes (odds ratio = 12.8, 95% CI: 2.78 to 58.88, P = .001), with a receiver operating characteristics curve of 0.752. CONCLUSIONS: FeNO measurements by the Vivatmo-me handheld device can serve as a biomarker and COVID-19 support tool for medical teams. These easy-to-use, portable, and noninvasive devices may serve as valuable ED bedside tools during a pandemic.


Subject(s)
COVID-19 , Exhalation , Biomarkers , Breath Tests , COVID-19/diagnosis , 59718 , Humans , Nitric Oxide , Prospective Studies , Severity of Illness Index
4.
Artif Intell Med ; 129: 102323, 2022 07.
Article in English | MEDLINE | ID: covidwho-1850671

ABSTRACT

Breath pattern analysis based on an electronic nose (e-nose), which is a noninvasive, fast, and low-cost method, has been continuously used for detecting human diseases, including the coronavirus disease 2019 (COVID-19). Nevertheless, having big data with several available features is not always beneficial because only a few of them will be relevant and useful to distinguish different breath samples (i.e., positive and negative COVID-19 samples). In this study, we develop a hybrid machine learning-based algorithm combining hierarchical agglomerative clustering analysis and permutation feature importance method to improve the data analysis of a portable e-nose for COVID-19 detection (GeNose C19). Utilizing this learning approach, we can obtain an effective and optimum feature combination, enabling the reduction by half of the number of employed sensors without downgrading the classification model performance. Based on the cross-validation test results on the training data, the hybrid algorithm can result in accuracy, sensitivity, and specificity values of (86 ± 3)%, (88 ± 6)%, and (84 ± 6)%, respectively. Meanwhile, for the testing data, a value of 87% is obtained for all the three metrics. These results exhibit the feasibility of using this hybrid filter-wrapper feature-selection method to pave the way for optimizing the GeNose C19 performance.


Subject(s)
COVID-19 , Electronic Nose , Breath Tests/methods , Cluster Analysis , Humans , Machine Learning
5.
J Breath Res ; 16(3)2022 05 26.
Article in English | MEDLINE | ID: covidwho-1830923

ABSTRACT

Exhaled breath vapor contains hundreds of volatile organic compounds (VOCs), which are the byproducts of health and disease metabolism, and they have clinical and diagnostic potential. Simultaneous collection of breath VOCs and background environmental VOCs is important to ensure analyses eliminate exogenous compounds from clinical studies. We present a mobile sampling system to extract gaseous VOCs onto commercially available sorbent-packed thermal desorption tubes. The sampler can be connected to a number of commonly available disposable and reusable sampling bags, in the case of this study, a Tedlar bag containing a breath sample. Alternatively, the inlet can be left open to directly sample room or environmental air when obtaining a background VOC sample. The system contains a screen for the operator to input a desired sample volume. A needle valve allows the operator to control the sample flow rate, which operates with an accuracy of -1.52 ± 0.63% of the desired rate, and consistently generated that rate with 0.12 ± 0.06% error across repeated measures. A flow pump, flow sensor and microcontroller allow volumetric sampling, as opposed to timed sampling, with 0.06 ± 0.06% accuracy in the volume extracted. Four samplers were compared by sampling a standard chemical mixture, which resulted in 6.4 ± 4.7% error across all four replicate modular samplers to extract a given VOC. The samplers were deployed in a clinical setting to collect breath and background/environmental samples, including patients with active SARS-CoV-2 infections, and the device could easily move between rooms and can undergo required disinfection protocols to prevent transmission of pathogens on the case exterior. All components required for assembly are detailed and are made publicly available for non-commercial use, including the microcontroller software. We demonstrate the device collects volatile compounds, including use of chemical standards, and background and breath samples in real use conditions.


Subject(s)
Breath Tests , Environmental Monitoring , Volatile Organic Compounds , Breath Tests/methods , COVID-19/prevention & control , Environmental Monitoring/methods , Exhalation , Humans , SARS-CoV-2/isolation & purification , Volatile Organic Compounds/analysis
7.
J Breath Res ; 16(3)2022 05 06.
Article in English | MEDLINE | ID: covidwho-1806207

ABSTRACT

COVID-19 detection currently relies on testing by reverse transcription polymerase chain reaction (RT-PCR) or antigen testing. However, SARS-CoV-2 is expected to cause significant metabolic changes in infected subjects due to both metabolic requirements for rapid viral replication and host immune responses. Analysis of volatile organic compounds (VOCs) from human breath can detect these metabolic changes and is therefore an alternative to RT-PCR or antigen assays. To identify VOC biomarkers of COVID-19, exhaled breath samples were collected from two sample groups into Tedlar bags: negative COVID-19 (n= 12) and positive COVID-19 symptomatic (n= 14). Next, VOCs were analyzed by headspace solid phase microextraction coupled to gas chromatography-mass spectrometry. Subjects with COVID-19 displayed a larger number of VOCs as well as overall higher total concentration of VOCs (p< 0.05). Univariate analyses of qualified endogenous VOCs showed approximately 18% of the VOCs were significantly differentially expressed between the two classes (p< 0.05), with most VOCs upregulated. Machine learning multivariate classification algorithms distinguished COVID-19 subjects with over 95% accuracy. The COVID-19 positive subjects could be differentiated into two distinct subgroups by machine learning classification, but these did not correspond with significant differences in number of symptoms. Next, samples were collected from subjects who had previously donated breath bags while experiencing COVID-19, and subsequently recovered (COVID Recovered subjects (n= 11)). Univariate and multivariate results showed >90% accuracy at identifying these new samples as Control (COVID-19 negative), thereby validating the classification model and demonstrating VOCs dysregulated by COVID are restored to baseline levels upon recovery.


Subject(s)
COVID-19 , Volatile Organic Compounds , Breath Tests/methods , Exhalation , Humans , SARS-CoV-2 , Volatile Organic Compounds/analysis
8.
J Breath Res ; 16(3)2022 06 15.
Article in English | MEDLINE | ID: covidwho-1784286

ABSTRACT

With the continued presence of COVID-19 worldwide, it has been a challenge for the breath research community to progress with clinical studies and travel restrictions have also limited the opportunities to meet up, share ideas and celebrate the latest advances. The Breath Biopsy Conference 2021 offered the chance to catch up with the latest breath research and to share progress that researchers in the community have been able to make in these difficult times. Limited opportunities for clinical research have led many in the field to look more closely at different methods for breath collection and have contributed to the growing calls for consistent standards in how results are reported, shared and even how breath studies themselves are carried out. As such, standardization was a key theme for this year's event and featured prominently in the keynotes, discussions and throughout many of the presentations. With over 900 registrants, almost 400 live attendees and 16 speakers, the Breath Biopsy Conference continues to bring together breath research leaders from around the world. This article provides an overview of the highlights from this event.


Subject(s)
Breath Tests , COVID-19 , Biopsy , Humans , Reproducibility of Results
9.
Anal Bioanal Chem ; 414(12): 3617-3624, 2022 May.
Article in English | MEDLINE | ID: covidwho-1750681

ABSTRACT

There is an urgent need to have reliable technologies to diagnose post-coronavirus disease syndrome (PCS), as the number of people affected by COVID-19 and related complications is increasing worldwide. Considering the amount of risks associated with the two chronic lung diseases, asthma and chronic obstructive pulmonary disease (COPD), there is an immediate requirement for a screening method for PCS, which also produce symptoms similar to these conditions, especially since very often, many COVID-19 cases remain undetected because a good share of such patients is asymptomatic. Breath analysis techniques are getting attention since they are highly non-invasive methods for disease diagnosis, can be implemented easily for point-of-care applications even in primary health care centres. Electronic (E-) nose technology is coming up with better reliability, ease of operation, and affordability to all, and it can generate signatures of volatile organic compounds (VOCs) in exhaled breath as markers of diseases. The present report is an outcome of a pilot study using an E-nose device on breath samples of cohorts of PCS, asthma, and normal (control) subjects. Match/no-match and k-NN analysis tests have been carried out to confirm the diagnosis of PCS. The prediction model has given 100% sensitivity and specificity. Receiver operating characteristics (ROC) has been plotted for the prediction model, and the area under the curve (AUC) is obtained as 1. The E-nose technique is found to be working well for PCS diagnosis. Our study suggests that the breath analysis using E-nose can be used as a point-of-care diagnosis of PCS.Trial registrationBreath samples were collected from the Kasturba Hospital, Manipal. Ethical clearance was obtained from the Institutional Ethics Committee, Kasturba Medical College, Manipal (IEC 60/2021, 13/01/2021) and Indian Council of Medical Research (ICMR) (CTRI/2021/02/031357, 06/02/2021) Government of India; trials were prospectively registered.


Subject(s)
Asthma , COVID-19 , Volatile Organic Compounds , Asthma/diagnosis , Breath Tests/methods , COVID-19/diagnosis , Electronic Nose , Exhalation , Humans , Pilot Projects , Reproducibility of Results , Technology , Volatile Organic Compounds/analysis
10.
J Breath Res ; 16(3)2022 04 28.
Article in English | MEDLINE | ID: covidwho-1740724

ABSTRACT

A Polymerase Chain Reaction (PCR) test of a nasal swab is still the 'gold standard' for detecting a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, PCR testing could be usefully complemented by non-invasive, fast, reliable, cheap methods for detecting infected individuals in busy areas (e.g. airports and railway stations) or remote areas. Detection of the volatile, semivolatile and non-volatile compound signature of SARS-CoV-2 infection by trained sniffer dogs might meet these requirements. Previous studies have shown that well-trained dogs can detect SARS-CoV-2 in sweat, saliva and urine samples. The objective of the present study was to assess the performance of dogs trained to detect the presence of SARS-CoV-2 in axillary-sweat-stained gauzes and on expired breath trapped in surgical masks. The samples were provided by individuals suffering from mild-to-severe coronavirus disease 2019 (COVID-19), asymptomatic individuals, and individuals vaccinated against COVID-19. Results: Seven trained dogs tested on 886 presentations of sweat samples from 241 subjects and detected SARS-CoV-2 with a diagnostic sensitivity (relative to the PCR test result) of 89.6% (95% confidence interval (CI): 86.4%-92.2%) and a specificity of 83.9% (95% CI: 80.3%-87.0%)-even when people with a low viral load were included in the analysis. When considering the 207 presentations of sweat samples from vaccinated individuals, the sensitivity and specificity were respectively 85.7% (95% CI: 68.5%-94.3%) and 86.0% (95% CI: 80.2%-90.3%). The likelihood of a false-positive result was greater in the two weeks immediately after COVID-19 vaccination. Four of the seven dogs also tested on 262 presentations of mask samples from 98 subjects; the diagnostic sensitivity was 83.1% (95% CI: 73.2%-89.9%) and the specificity was 88.6% (95% CI: 83.3%-92.4%). There was no difference (McNemar's testP= 0.999) in the dogs' abilities to detect the presence of SARS-CoV-2 in paired samples of sweat-stained gauzes vs surgical masks worn for only 10 min. Conclusion: Our findings confirm the promise of SARS-CoV-2 screening by detection dogs and broaden the method's scope to vaccinated individuals and easy-to-obtain face masks, and suggest that a 'dogs + confirmatory rapid antigen detection tests' screening strategy might be worth investigating.


Subject(s)
COVID-19 , Animals , Breath Tests , COVID-19 Vaccines , Dogs , Humans , RNA, Viral/analysis , SARS-CoV-2 , Sweat/chemistry , Working Dogs
11.
Sci Rep ; 12(1): 4370, 2022 03 14.
Article in English | MEDLINE | ID: covidwho-1740483

ABSTRACT

Breathomics is widely emerging as a strategy for non-invasive diagnosis of respiratory inflammation. In this study, we have evaluated the metabolic signals associated with Coronavirus (SARS COV-2), mainly the release of nitric oxide in breath. We have demonstrated the utility of a breath analyzer-based sensor platform for the detection of trace amounts of this target species. The sensor surface is modified with Room Temperature Ionic Liquid (RTIL) that allows faster diffusion of the target gas and can be used for gas sensing application. A low limit of detection (LOD) of 50 parts per billion has been achieved with a 95% confidence interval for detection of nitric oxide.. This inhouse designed sensor is incorporated into a breath analyzer system that displays enhanced sensitivity, specificity, linearity, and reproducibility for NO gas monitoring. The developed sensor platform can detect target concentrations of NO ranging from 50 to 250 ppb, using 1-Ethyl-3-methylimidazolium Tetrafluoroborate ([EMIM]BF4) as RTIL and displays fast response time of 5 s, thereby allowing easy detection of the target gas species. The sensor successfully quantifies the diffusion current and charge modulations arising within the electrical double layer from the RTIL-NO interactions through DC-based chronoamperometry (CA). The subjects tested negative and positive are significantly different (p < 0.01). The prototype can potentially be used for human health monitoring and screening, especially during the pandemic due to its portability, small size, an embedded RTIL sensing element, integrability with a low-power microelectronic device, and an IoT interface.


Subject(s)
COVID-19 , Ionic Liquids , Breath Tests , COVID-19/diagnosis , Humans , Reproducibility of Results , Technology
12.
Sci Rep ; 12(1): 3884, 2022 03 10.
Article in English | MEDLINE | ID: covidwho-1740465

ABSTRACT

Current SARS-CoV-2 vaccines are effective, but long-term protection is threatened by the emergence of virus variants. We generated a virosome vaccine containing the Beta spike protein and compared its immunogenicity in mice to a virosome vaccine containing the original Wuhan spike. Two administrations of the virosomes induced potent SARS-CoV-2 neutralizing antibodies in both vaccine groups. The level of autologous neutralization in Beta-vaccinated mice was similar to the level of autologous neutralization in Wuhan-vaccinated mice. However, heterologous neutralization to the Wuhan strain in Beta-vaccinated mice was 4.7-fold lower than autologous neutralization, whereas heterologous neutralization to the Beta strain in Wuhan-vaccinated mice was reduced by only 1.9-fold compared to autologous neutralization levels. In addition, neutralizing activity against the D614G, Alpha and Delta variants was also significantly lower after Beta spike vaccination than after Wuhan spike vaccination. Our results show that Beta spike vaccination induces inferior neutralization breadth. These results are informative for programs aimed to develop broadly active SARS-CoV-2 vaccines.


Subject(s)
COVID-19 Vaccines/therapeutic use , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Breath Tests , COVID-19 Vaccines/immunology , Female , Mice , Mice, Inbred BALB C , Neutralization Tests , Vaccines, Virosome/immunology , Vaccines, Virosome/therapeutic use
13.
J Breath Res ; 16(2)2022 03 18.
Article in English | MEDLINE | ID: covidwho-1722148

ABSTRACT

In 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged to cause high viral infectivity and severe respiratory illness in humans (COVID-19). Worldwide, limited pandemic mitigation strategies, including lack of diagnostic test availability, resulted in COVID-19 overrunning health systems and spreading throughout the global population. Currently, proximal respiratory tract (PRT) specimens such as nasopharyngeal swabs are used to diagnose COVID-19 because of their relative ease of collection and applicability in large scale screening. However, localization of SARS-CoV-2 in the distal respiratory tract (DRT) is associated with more severe infection and symptoms. Exhaled breath condensate (EBC) is a sample matrix comprising aerosolized droplets originating from alveolar lining fluid that are further diluted in the DRT and then PRT and collected via condensation during tidal breathing. The COVID-19 pandemic has resulted in recent resurgence of interest in EBC collection as an alternative, non-invasive sampling method for the staging and accurate detection of SARS-CoV-2 infections. Herein, we review the potential utility of EBC collection for detection of SARS-CoV-2 and other respiratory infections. While much remains to be discovered in fundamental EBC physiology, pathogen-airway interactions, and optimal sampling protocols, EBC, combined with emerging detection methods, presents a promising non-invasive sample matrix for detection of SARS-CoV-2.


Subject(s)
COVID-19 , Respiratory Tract Infections , Breath Tests/methods , Humans , Pandemics , SARS-CoV-2
14.
BMJ Open ; 12(2): e057271, 2022 Feb 25.
Article in English | MEDLINE | ID: covidwho-1714416

ABSTRACT

INTRODUCTION: Pancreatic cancer (PC) is the fifth leading cause of cancer-related death in the UK. The incidence of PC is increasing, with little or no improvement in overall survival and the best chance for long-term survival in patients with PC relies on early detection and surgical resection. In this study, we propose the use of a diagnostic algorithm that combines tests of pancreatic exocrine function (faecal elastase-1 (FE-1) test and the 13C-mixed triglyceride (13C-MTG) breath test) to identify patients with PC that urgently needs imaging studies. METHODS AND ANALYSIS: This prospective pilot (proof of concept) study will be carried out on 25 patients with resectable PC, 10 patients with chronic pancreatitis and 25 healthy volunteers. This study will construct a predictive algorithm for PC, using two tests of pancreatic exocrine function, FE-1 test and the 13C-MTG breath test. Continuous flow isotope ratio mass spectrometry in the 13C-MTG breath test will be used to analyse enriched 13CO2 in exhaled breath samples. The additional predictive benefit of other potential biomarkers of PC will also be considered. Potential biomarkers of PC showing abilities to discriminate between patients with PC from healthy subjects or patients with chronic pancreatitis will be selected by metabolomic analysis. ETHICS AND DISSEMINATION: The study was approved by the North of Scotland Research and Ethics Committee on 1 October 2020 (reference: 20/NS/0105, favourable opinion granted). The results will be disseminated in presentations at academic national/international conferences and publication in peer-review journals.


Subject(s)
Exocrine Pancreatic Insufficiency , Pancreatic Neoplasms , Pancreatitis, Chronic , Biomarkers , Breath Tests/methods , Early Detection of Cancer/adverse effects , Exocrine Pancreatic Insufficiency/diagnosis , Exocrine Pancreatic Insufficiency/epidemiology , Exocrine Pancreatic Insufficiency/etiology , Humans , Pancreatic Elastase , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/diagnosis , Pancreatitis, Chronic/complications , Pancreatitis, Chronic/diagnosis , Pilot Projects , Prospective Studies , Triglycerides
15.
Sensors (Basel) ; 22(3)2022 Feb 06.
Article in English | MEDLINE | ID: covidwho-1686946

ABSTRACT

Early-stage disease diagnosis is of particular importance for effective patient identification as well as their treatment. Lack of patient compliance for the existing diagnostic methods, however, limits prompt diagnosis, rendering the development of non-invasive diagnostic tools mandatory. One of the most promising non-invasive diagnostic methods that has also attracted great research interest during the last years is breath analysis; the method detects gas-analytes such as exhaled volatile organic compounds (VOCs) and inorganic gases that are considered to be important biomarkers for various disease-types. The diagnostic ability of gas-pattern detection using analytical techniques and especially sensors has been widely discussed in the literature; however, the incorporation of novel nanomaterials in sensor-development has also proved to enhance sensor performance, for both selective and cross-reactive applications. The aim of the first part of this review is to provide an up-to-date overview of the main categories of sensors studied for disease diagnosis applications via the detection of exhaled gas-analytes and to highlight the role of nanomaterials. The second and most novel part of this review concentrates on the remarkable applicability of breath analysis in differential diagnosis, phenotyping, and the staging of several disease-types, which are currently amongst the most pressing challenges in the field.


Subject(s)
Body Fluids , Volatile Organic Compounds , Breath Tests , Exhalation , Gases , Humans
16.
Respir Med ; 193: 106745, 2022 03.
Article in English | MEDLINE | ID: covidwho-1648477

ABSTRACT

The nature of the inflammatory and fibrotic processes found in patients with post-COVID-19 syndrome makes it possible to speculate that in such patients fractional exhaled nitric oxide (FeNO) may be a useful biomarker. Consequently, we set out to verify the consistency of this hypothesis. We consecutively enrolled 68 post-COVID patients after being hospitalized for persistent clinical manifestations within 2 months from disease onset and 29 healthy volunteers as control group. None of post-COVID patients had bronchial asthma or were being treated with a corticosteroid. Only 19 out of 68 post-COVID-19 patients reported a FeNO value > 25 ppb. The mean FeNO value in post-COVID-19 patients was 18.55 ppb (95% CI: 15.50 to 21.58), while in healthy subjects it was 17.46 ppb (95% CI: 15.75 to 19.17). The mean difference was not statistically significant (P = 0.053). However, the mean FeNO value of post-COVID-19 patients was higher in men than in women (20.97 ppb; 95% CI: 16.61 to 25.33 vs 14.36 ppb; 95% CI: 11.11 to 17.61) with a difference between the two sexes that was statistically significant (P = 0.016). Mean FeNO was 14.89 ppb (95% CI: 10.90 to 18.89) in patients who had been treated with systemic corticosteroids because of their COVID-19, and 20.80 ppb (95% CI: 16.56 to 25.04) in those who had not taken them, with a difference that was statistically significant (P = 0.043). The data generated in this study suggest that measurement of FeNO is not useful as a biomarker in post-COVID-19 patient. However, this hypothesis needs solid validation with additional specifically designed studies.


Subject(s)
COVID-19 , Biomarkers , Breath Tests , COVID-19/complications , Exhalation , Female , Humans , Male , Nitric Oxide , SARS-CoV-2
17.
J Breath Res ; 16(2)2022 03 04.
Article in English | MEDLINE | ID: covidwho-1648455

ABSTRACT

Background. The SARS-CoV-2 pandemic changed the way the society functioned. The race to develop a rapid, non-invasive, widely available test resulted in multiple studies examining the potential of breath to be that 'game changing test'. Breath sampling is a non-invasive point of care test, but SAR-CoV-2 has introduced a level of danger into collection and analysis that requires a change in workflow to keep staff and participants safe. We developed a SARS-CoV 2 breath test work flow for collection and processing of breath samples in an ambulatory care setting and prospectively evaluated the protocol. Protocol development included testing the effect of respiratory filters on the integrity and reproducibility of breath samples.Methods. Prospective, observational study conducted at community COVID-19 testing sites, collecting breath samples from patients presenting for RT-PCR testing. Breath was collected via Tedlar®, and/or BioVOC-2™ as well as an environmental sample for all participants. Samples were transferred to Tenex tubes, dry purged and analyzed using a Centri automated sample introduction machine, GC, and a Bench-ToF-HD.Results. We successfully collected and processed 528 breath samples from 393 participants at community-based ambulatory COVID-19 test sites. The majority of samples were collected before vaccines were available and throughout the emergence of the Delta Variant. No staff member was infected.Conclusion. We demonstrated a safe workflow for the collection, handling, transport, storage, and analysis of breath samples during the pandemic collecting highly infectious SARS-CoV-2 positive breath samples. This was done without filters as they added complexity to the breath matrix, jeopardizing the sample integrity.


Subject(s)
COVID-19 Testing , COVID-19 , Animals , Breath Tests , Humans , Prospective Studies , Reproducibility of Results , SARS-CoV-2
18.
J Breath Res ; 16(2)2022 02 07.
Article in English | MEDLINE | ID: covidwho-1642273

ABSTRACT

The real-time PCR (RT-PCR) on nasopharyngeal swabs (NPS) is the gold standard for the diagnosis of SARS-CoV-2. The exhaled breath condensate (EBC) is used to perform collection of biological fluid condensed in a refrigerated device from deep airways' exhaled air. We aimed to verify the presence of SARS-CoV-2 virus in the EBC from patients with confirmed SARS-CoV-2 infection by RT-PCR, and to determine if the EBC may represent a valid alternative to the NPS. Seventeen consecutive patients admitted to the Emergency Department of the Policlinico were enrolled in the present study with RT-PCR, clinical and radiological evidence of SARS-CoV-2. Within 24 h from the NPS collection the EBC collection was performed on SARS-CoV-2 positive patients. Informed written consent was gathered and the Ethic Committee approved the study. The mean age of patients was 60 years (24-92) and 64.7% (11/17) were male. Patient n.9 and n.17 died. All NPS resulted positive for SARS-CoV-2 at RT-PCR. RT-PCR on EBC resulted negative for all but one patients (patient n.12). In this study we did not find any correlation between positive NPS and the EBC in all but one patients enrolled. Based on these data which greatly differ from previous reports on the topic, this study opens several questions related to small differences in the complex process of EBC collection and how EBC could be really standardized for the diagnosis of SARS-CoV-2 infection. Further studies will be warranted to deepen this topic.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Breath Tests , COVID-19 Testing , Exhalation , Humans , Male , Middle Aged , Young Adult
19.
Angew Chem Int Ed Engl ; 61(9): e202112995, 2022 02 21.
Article in English | MEDLINE | ID: covidwho-1633678

ABSTRACT

The transmission of SARS-CoV-2 coronavirus has led to the COVID-19 pandemic. Nucleic acid testing while specific has limitations for mass surveillance. One alternative is the main protease (Mpro ) due to its functional importance in mediating the viral life cycle. Here, we describe a combination of modular substrate and gold colloids to detect Mpro via visual readout. The strategy involves zwitterionic peptide that carries opposite charges at the C-/N-terminus to exploit the specific recognition by Mpro . Autolytic cleavage releases a positively charged moiety that assembles the nanoparticles with rapid color changes (t<10 min). We determine a limit of detection for Mpro in breath condensate matrices <10 nM. We further assayed ten COVID-negative subjects and found no false-positive result. In the light of simplicity, our test for viral protease is not limited to an equipped laboratory, but also is amenable to integrating as portable point-of-care devices including those on face-coverings.


Subject(s)
COVID-19/diagnosis , Coronavirus 3C Proteases/metabolism , Peptides/metabolism , SARS-CoV-2/metabolism , Biomarkers/metabolism , Breath Tests , COVID-19/virology , Colorimetry/methods , Humans , Limit of Detection , Proteolysis
20.
Clin Chem ; 68(1): 43-51, 2021 12 30.
Article in English | MEDLINE | ID: covidwho-1591716

ABSTRACT

BACKGROUND: Starkly highlighted by the current COVID-19 pandemic, infectious diseases continue to have an outsized impact on human health worldwide. Diagnostic testing for infection can be challenging due to resource limitations, time constraints, or shortcomings in the accuracy of existing diagnostics. Rapid, simple diagnostics are highly desirable. There is increasing interest in the development of diagnostics that use exhaled breath analysis as a convenient and safe diagnostic method, as breath sampling is noninvasive, secure, and easy to perform. Volatile organic compounds (VOCs) present in exhaled breath reflect the fingerprint of the underlying metabolic and biophysical processes during disease. CONTENT: In this review, we overview the major biomarkers present in exhaled breath in infectious diseases. We outline the promising recent advances in breath-based diagnosis of respiratory infections, including those caused by influenza virus, SARS-CoV-2, Mycobacterium tuberculosis, Pseudomonas aeruginosa, and Aspergillus fumigatus. In addition, we review the current landscape of diagnosis of 2 other globally important infections: Helicobacter pylori gastrointestinal infection and malaria. SUMMARY: Characteristic and reproducible breath VOCs are associated with several infectious diseases, suggesting breath analysis as a promising strategy for diagnostic development. Ongoing challenges include poor standardization of breath collection and analysis and lack of validation studies. Further research is required to expand the applicability of breath analysis to clinical settings.


Subject(s)
Breath Tests , Communicable Diseases/diagnosis , Volatile Organic Compounds , Exhalation , Humans , Volatile Organic Compounds/analysis
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