{"doi":"10.1016/j.ebiom.2020.103183","title":"A breath of fresh air – the potential for COVID-19 breath diagnostics","abstract":"As the world continues to grapple with the ongoing SARS-CoV-2 pandemic, it remains clear that frequent and widespread virus testing is a valuable tool to understand disease spread and to guide public health actions by communities and governments. To date, most traditional diagnostic tests continue to rely on established polymerase chain reaction (PCR) technologies, which have proven to be quite robust as a tool for mass screening and remain the gold standard within modern medicine. When employed using standardized protocols, PCR typically has a high accuracy and high specificity (eg, low false positives and low false negatives). Early in the pandemic, there were challenges to quickly establish and distribute the best testing methods. Once resolved, the test was widely and successfully rolled out in protocols across the world. However, other challenges have emerged when using this as a tool to combat COVID-19 spread. For one, there are known sampling issues with nasopharyngeal PCR tests. While PCR itself is incredibly robust, it relies on collecting samples of actively amplifying viral genetic material. Though uncommon, it is possible to “miss” swabbing an area with active viral loads, which leads to a false-negative test result. There have been many more issues with the operational logistics and product supply chains that have strained testing systems during this public health crisis. The liquid reagents needed for the PCR test and the nasal swabs are in high demand, thus limiting availability in some locations causing alterations to planned testing protocols. Finally, although PCR is very reliable, there can be a significant time delay between sampling and when the results are available – hours-to-days, depending on processing capabilities of the test site. Recently, a new approach to viral diagnostics has been considered by examining exhaled breath for signatures of the host-response to infection [[1]Metabolomics of exhaled breath in critically ill COVID-19 patients: a pilot study.EBioMedicine. 2020; (in press)Google Scholar]. For several decades, it has been known that endogenously produced volatile organic compounds (VOCs) are present in exhaled breath, and these are frequent targets of breath diagnostics research and represent metabolic endpoints that can be quickly assessed for health information [[2]Beauchamp J. Davis C. Pleil J. Breathborne biomarkers and the human volatilome. Elsevier Science, 2020Google Scholar]. There are also reports of scent dogs being trained to detect human diseases, and observations of this phenomenon have also been recently expanded to include COVID-19 diagnosis [[3]Jendrny P. et al.Scent dog identification of samples from COVID-19 patients – a pilot study.BMC Infect Dis. 2020; 20: 536Crossref PubMed Scopus (112) Google Scholar, [4]Grandjean D, et al. Detection dogs as a help in the detection of COVID-19 Can the dog alert on COVID-19 positive persons by sniffing axillary sweat samples? Proof-of-concept study. bioRxiv, 2020: p. 2020.06.03.132134.Google Scholar]. While the cellular and molecular mechanisms and fundamental understandings of breath signature VOC generation are still being developed, some prior work in cell culture models pointed to viral-associated breath VOCs for both rhinovirus [[5]Schivo M. et al.Volatile emanations from in vitro airway cells infected with human rhinovirus.J Breath Res. 2014; 8037110Crossref Scopus (48) Google Scholar] and seasonal influenza respiratory tract infections [[6]Aksenov A.A. et al.Cellular Scent of Influenza Virus Infection.ChemBioChem. 2014; 15: 1040-1048Crossref PubMed Scopus (62) Google Scholar]. Specific oxidative stress VOCs were also observed post-vaccination in another previous study [[7]Phillips M. et al.Effect of influenza vaccination on oxidative stress products in breath.J Breath Res. 2010; 4026001Crossref Scopus (52) Google Scholar], when a nasally-delivered attenuated live virus vaccine was used. This was also followed by at least one p","journal":"EBioMedicine","year":2021,"id":170556,"datarank":0.49983067652628066,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":0.0,"self_endowment_contribution":0.49983067652628066,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":341808,"name":"Michael Schivo","orcid":"0000-0002-5394-5687","position":1,"is_corresponding":false},{"id":313854,"name":"Nicholas J. 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