Limitations and opportunities in breath research in the face of the COVID-19 pandemic

Looking back to the beginning of 2020, the unremarkable start to a seemingly normal year was suddenly upheaved when, late January, the World Health Organization announced an 'international health emergency' in response to an apparent viral outbreak in Wuhan, China, followed in March by the declaration of a global pandemic. These unprecedented turn of events had a profound and lasting impact on diverse aspects of scientific research across many disciplines, with breath research being no exception. Until the pandemic, the collection and analysis of exhaled breath was considered relatively low risk due to non-invasive sampling and the benign nature of breath, hitherto cited as a major advantage in both research and clinical applications. With the outbreak of the pandemic, however, the landscape of breath research was changed abruptly and dramatically, as it became necessary to recognize breath as a potentially contagious specimen requiring precautions in handling to minimize risk of viral transmission and infection [1, 2]. Yet, accompanying this major limitation was a great opportunity for breath through its potential to detect coronavirus disease 2019 (COVID-19), a respiratory infection that is transmitted via exhaled air and aerosols [3, 4]. Consequently, there were expectations that breath research might play a key role in developing early detection methods for this disease, which would represent a game-changer in pandemic control endeavours [1, 5, 6].

In the light of these circumstances, and recognizing the limitations and opportunities for breath research, Journal of Breath Research quickly set out to launch a special issue focused on COVID-19-related research and clinical applications. In particular, a major remit of this journal collection was to solicit articles to establish safety measures for breath collection and analysis. Further, this special issue represented a contribution by the journal—encompassing the publisher and the editorial board—to contribute to research efforts in the scientific community in the face of the pandemic by establishing a platform to facilitate the exchange of high-quality, transparent scientific communications and encourage collaborative efforts on utilizing breath for COVID-19 detection. An editorial at the start of the pandemic by the journal editors, Pleil et al, effectively set the tone for this special issue, highlighting points of consideration during this unparalleled scenario, as well as announcing the requirement that all research articles submitted to the journal henceforth must disclose the procedures undertaken to ensure appropriate laboratory and clinical safety [1]. The editorial was later accompanied by a perspectives article in which Sawano et al outlined considerations for clinical trials in a frank and transparent brief [7]. Another editorial by Pleil et al presented a rationale for mask wearing based on studies of exhaled breath aerosol collection from the breath research community [4, 8, 9].

The present editorial closes the special issue, Breath Research on COVID-19 and Related Applications: Developments, Discoveries and Deliberations ⁵ , which consists of three editorials (including this one) [1, 4], 12 research papers [10–21], four perspectives articles [2, 5, 7, 22], two notes [3, 6], and two topical reviews [23, 24]; a total of 23 articles. The majority of articles report on efforts towards the diagnosis of COVID-19 using breath, either via detection of viral RNA in exhaled breath condensate (EBC) [7, 12, 13, 23] or through determining the changes that manifest in the volatile organic compound (VOC) profile of breath gas associated with an altered metabolism that accompanies viral infection [5, 6, 11, 18, 19].

Viral spread or its prevention were the subject of two papers, one by Tran et al that examined the efficacy of face masks in reducing viral transmission through a systematic review and network meta-analysis [21] and another by Vanden Driessche et al that focussed on the role of coughing as a vector of infection [3]. Two papers present methods to minimize risk of infection through sample handling by viral inactivation, one by Lomonaco et al relating to sampling breath volatiles on sorbent tubes [16], the other by Hu et al on the collection of EBC samples [17]. In a related paper on safety aspects, Myers et al presented a protocol to minimize risk of infection when collecting breath samples in large cohort trials [15].

The four perspectives articles treated different COVID-related topics. In a similar context to the aforementioned paper by Myers et al, the paper by Sawano et al presented safety measures during EBC collection to reduce the likelihood of infection amongst medical staff and patients, which was complemented in the perspective article by Mimura et al in which aspects for the prevention of hospital-acquired infection of COVID-19 are highlighted [22]. Similarly, Chandrapalan et al provided a perspective on the implications of breath testing in the clinical and research arena [2]. In their paper leading with the title The Scent of COVID-19, Lamote et al present a treatise on physiology associated with the potential manifestation of viral infection in breath gas, as might be exploited in a prospective test [5]. In a complementary note by Gould et al, the authors revisited the state of the art in viral detection via breath analysis, discussing host response as well as analytical methods that present promising approaches for this endeavour [6]. A similar review was penned by Nwanochie and Linnes relating to the detection of viral infection in EBC [23]. The topical review by Ricciardolo et al discussed the potential therapeutic effect of nitric oxide inhalation in treating severe COVID-19 [24].

Amongst the research articles, the papers by Acar et al and Wood et al examined the phenomenon of 'long COVID' from the viewpoints of respiratory physiology and end-tidal carbon dioxide levels and lung and peripheral muscle performance, respectively [10, 20], while Patrucco et al looked at the prevalence of comorbid mycotic infection amongst patients undergoing bronchoalveolar lavage [14]. Evidence for the prospective use of breath volatiles for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was presented in three research articles using different approaches. The papers by Chen et al and Steppert et al both report on the detection of breath VOCs using ion mobility spectrometry, albeit using different compound pre-separation methods, either gas chromatography [19] or multi-capillary column [11]. Taking a completely different approach, Devillier et al presented evidence for a COVID-19 test using biomedical dogs as the modality for examining axillary sweat and breath samples [18]. In two companion studies, Sawano et al provided data on the detection of SARS-CoV-2 infection via EBC analysis [12, 13].

The articles published in this special issue are a testament to the breath research community rising to the challenges faced in past two and a half years of turbulence. At the time of writing, these articles have amassed over 53 000 downloads and have been cited collectively 231 times. These achievements underscore the utility of establishing journal collections under such circumstances to act as a platform that provides the scientific community with the latest knowledge in a single repository. Critically, this can facilitate rapid progress in endeavours to develop diagnostic approaches or screening tools, while ensuring the safety in research efforts. As such, we—the guest editors—would like to express our humble thanks to all authors for their important contributions to this journal collection, as well as our gratitude to the impartial yet critical reviewers for their constructive feedback, and, above all, to the readership of Journal of Breath Research for their interest in this collection. Despite the persistently undulating numbers of COVID-positive cases, the world seems to be making a careful but steady move towards a post-pandemic era. Nevertheless, given the past outbreaks of viral infections in recent decades, including SARS, the scientific role of breath research and the opportunities it represents in response to the hitherto enduring pandemic—or the next one—may grow in the future. As such, although this current journal collection concludes with this editorial, the next Journal of Breath Research special issue is under preparation, with a focus on the next stages of developments in the field of breath research in the context of COVID-19.

No new data were created or analysed in this study.