Wearable Collector for Noninvasive Sampling of SARS-CoV-2 from Exhaled Breath for Rapid Detection.

Airborne transmission of exhaled virus can rapidly spread, thereby increasing disease progression from local incidents to pandemics. Due to the COVID-19 pandemic, states and local governments have enforced the use of protective masks in public and work areas to minimize the disease spread. Here, we have leveraged the function of protective face coverings toward COVID-19 diagnosis. We developed a user-friendly, affordable, and wearable collector. This noninvasive platform is integrated into protective masks toward collecting airborne virus in the exhaled breath over the wearing period. A viral sample was sprayed into the collector to model airborne dispersion, and then the enriched pathogen was extracted from the collector for further analytical evaluation. To validate this design, qualitative colorimetric loop-mediated isothermal amplification, quantitative reverse transcription polymerase chain reaction, and antibody-based dot blot assays were performed to detect the presence of SARS-CoV-2. We envision that this platform will facilitate sampling of current SARS-CoV-2 and is potentially broadly applicable to other airborne diseases for future emerging pandemics.

Sensors for the detection of ammonia as a potential biomarker for health screening.

The presence of ammonia within the body has long been linked to complications stemming from the liver, kidneys, and stomach. These complications can be the result of serious conditions such as chronic kidney disease (CKD), peptic ulcers, and recently COVID-19. Limited liver and kidney function leads to increased blood urea nitrogen (BUN) within the body resulting in elevated levels of ammonia in the mouth, nose, and skin. Similarly, peptic ulcers, commonly from H. pylori, result in ammonia production from urea within the stomach. The presence of these biomarkers enables a potential screening protocol to be considered for frequent, non-invasive monitoring of these conditions. Unfortunately, detection of ammonia in these mediums is rather challenging due to relatively small concentrations and an abundance of interferents. Currently, there are no options available for non-invasive screening of these conditions continuously and in real-time. Here we demonstrate the selective detection of ammonia using a vapor phase thermodynamic sensing platform capable of being employed as part of a health screening protocol. The results show that our detection system has the remarkable ability to selectively detect trace levels of ammonia in the vapor phase using a single catalyst. Additionally, detection was demonstrated in the presence of interferents such as carbon dioxide (CO2) and acetone common in human breath. These results show that our thermodynamic sensors are well suited to selectively detect ammonia at levels that could potentially be useful for health screening applications.

Stability of volatile organic compounds in sorbent tubes following SARS-CoV-2 inactivation procedures.

COVID-19 is a highly transmissible respiratory illness that has rapidly spread all over the world causing more than 115 million cases and 2.5 million deaths. Most epidemiological projections estimate that the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus causing the infection will circulate in the next few years and raise enormous economic and social issues. COVID-19 has a dramatic impact on health care systems and patient management, and is delaying or stopping breath research activities due to the risk of infection to the operators following contact with patients, potentially infected samples or contaminated equipment. In this scenario, we investigated whether virus inactivation procedures, based on a thermal treatment (60 °C for 1 h) or storage of tubes at room temperature for 72 h, could be used to allow the routine breath analysis workflow to carry on with an optimal level of safety during the pandemic. Tests were carried out using dry and humid gaseous samples containing about 100 representative chemicals found in exhaled breath and ambient air. Samples were collected in commercially available sorbent tubes, i.e. Tenax GR and a combination of Tenax TA, Carbograph 1TD and Carboxen 1003. Our results showed that all compounds were stable at room temperature up to 72 h and that sample humidity was the key factor affecting the stability of the compounds upon thermal treatment. Tenax GR-based sorbent tubes were less impacted by the thermal treatment, showing variations in the range 20%-30% for most target analytes. A significant loss of aldehydes and sulphur compounds was observed using carbon molecular sieve-based tubes. In this case, a dry purge step before inactivation at 60 °C significantly reduced the loss of the target analytes, whose variations were comparable to the method variability. Finally, a breath analysis workflow including a SARS-CoV-2 inactivation treatment is proposed.

Addressing Reduced Laboratory-Based Pulmonary Function Testing During a Pandemic.

To reduce the spread of the severe acute respiratory syndrome coronavirus 2, many pulmonary function testing (PFT) laboratories have been closed or have significantly reduced their testing capacity. Because these mitigation strategies may be necessary for the next 6 to 18 months to prevent recurrent peaks in disease prevalence, fewer objective measurements of lung function will alter the diagnosis and care of patients with chronic respiratory diseases. PFT, which includes spirometry, lung volume, and diffusion capacity measurement, is essential to the diagnosis and management of patients with asthma, COPD, and other chronic lung conditions. Both traditional and innovative alternatives to conventional testing must now be explored. These may include peak expiratory flow devices, electronic portable spirometers, portable exhaled nitric oxide measurement, airwave oscillometry devices, and novel digital health tools such as smartphone microphone spirometers and mobile health technologies along with integration of machine learning approaches. The adoption of some novel approaches may not merely replace but could improve existing management strategies and alter common diagnostic paradigms. With these options comes important technical, privacy, ethical, financial, and medicolegal barriers that must be addressed. However, the coronavirus disease 19 pandemic also presents a unique opportunity to augment conventional testing by including innovative and emerging approaches to measuring lung function remotely in patients with respiratory disease. The benefits of such an approach have the potential to enhance respiratory care and empower patient self-management well beyond the current global pandemic.

A short perspective on a COVID-19 clinical study: 'diagnosis of COVID-19 by RT-PCR using exhale breath condensate samples'.

Diagnosis of SARS-COV-2 infection (COVID-19) is currently based on detection of the viral RNA in nasopharyngeal swab samples by reverse transcription polymerase chain reaction (RT-PCR). However, sampling via nasopharyngeal swabs frequently provokes sneezing or coughing, which results in increased risk of the viral dissemination and environmental contamination. Furthermore, the sensitivity associated with the PCR tests s limited to 60%-70%, which is mainly attributable to technical deficiency in sampling. Given that the disease is transmitted via exhaled aerosol and droplets, and that the exhaled breath condensate (EBC) is the established modality for sampling exhaled aerosol, detection of the viral RNA in EBC is a promising approach for safe and efficient diagnosis of the disease. Subjects are those patients who are diagnosed with COVID-19 by positive nasopharyngeal swab PCR test and admitted to Saitama Medical Center, Japan. EBC samples will be collected using an R-tube® or R-tubeVent® device. Collected EBC samples will be introduced into a nucleic acid purifier. The purified nucleic acids will undergo amplification through RT-PCR for detection and quantification of SARS-COV-2 RNA. To date we have collected eight samples from seven subjects. Among them, two samples from two subjects tested positive for SARS-COV-2 RNA by the RT-PCR. Reflecting the second wave of COVID-19 prevalence in Japan, new admissions of COVID-19 patients to the Saitama Medical Center are increasing, and we are expecting to collect at least 50 EBC samples from 25 patients before the end of this year.

Multiplexed Nanomaterial-Based Sensor Array for Detection of COVID-19 in Exhaled Breath.

This article reports on a noninvasive approach in detecting and following-up individuals who are at-risk or have an existing COVID-19 infection, with a potential ability to serve as an epidemic control tool. The proposed method uses a developed breath device composed of a nanomaterial-based hybrid sensor array with multiplexed detection capabilities that can detect disease-specific biomarkers from exhaled breath, thus enabling rapid and accurate diagnosis. An exploratory clinical study with this approach was examined in Wuhan, China, during March 2020. The study cohort included 49 confirmed COVID-19 patients, 58 healthy controls, and 33 non-COVID lung infection controls. When applicable, positive COVID-19 patients were sampled twice: during the active disease and after recovery. Discriminant analysis of the obtained signals from the nanomaterial-based sensors achieved very good test discriminations between the different groups. The training and test set data exhibited respectively 94% and 76% accuracy in differentiating patients from controls as well as 90% and 95% accuracy in differentiating between patients with COVID-19 and patients with other lung infections. While further validation studies are needed, the results may serve as a base for technology that would lead to a reduction in the number of unneeded confirmatory tests and lower the burden on hospitals, while allowing individuals a screening solution that can be performed in PoC facilities. The proposed method can be considered as a platform that could be applied for any other disease infection with proper modifications to the artificial intelligence and would therefore be available to serve as a diagnostic tool in case of a new disease outbreak.

Breath diagnostics in the era of SARS-CoV-2-clinical and research arena.

The emergence of the SARS-CoV-2 pandemic has transformed not just healthcare, but also economic systems on a global scale. Despite significant efforts to contain the infection, it continues to spread. Stringent infection control measures have been taken to minimise the transmission between individuals and healthcare workers, especially those undertaking aerosol generating medical procedures. The uncertainties surrounding infection transmission through breath tests in particular, and to some extent faecal testing, will invariably cause concerns amongst both the patients and healthcare workers. It is therefore pertinent that all of the necessary measures are adopted to minimise risk of spreading. In this article, we summarise the physiology and virulence of SARS-CoV-2 and discuss the implications for breath testing (in both the clinical and research arena) as well as outlining methods to mitigate these risks.