The scent of COVID-19: viral (semi-)volatiles as fast diagnostic biomarkers?

The COVID-19 pandemic pressurizes the healthcare system. Protective measures against SARS-CoV-2 infection, like social distancing or isolation, are being taken too late and COVID-19 symptoms are non-specific and can resemble those from rhinoviral infection or influenza, causing a rush of anxious patients with (mild) symptoms to the hospitals. Furthermore, COVID-19 diagnosis is made by taking swabs from the upper of lower respiratory tract, which is not only an unpleasant experience for the patient, but is also time-consuming. Therefore, a fast differential diagnosis between SARS-COV-2, influenza or rhinovirus infection would allow to optimize the hospital management and hospitalize those patients with proven COVID-19 disease, where other patients can easily recover at home. Breath analysis could therefore be explored investigating both volatile organic compounds (VOC) and exhaled breath condensate (EBC) and aerosols (EBA) in a non-invasive manner, without discomforting the patient. However, breath research is highly affected since human-mediated transmission of viral particles through breath is of high concern. Nevertheless, breathomics can provide fast results and the sampling materials can be cleaned and autoclaved thoroughly, minimizing the risk for cross-contamination. Breath analysis also allows the breath sample to be taken by the patient himself, hence, considering the social distancing measures and protecting health care workers. In this article, we summarize 3 pathways in which SARS-CoV-2 could generate specific VOCs. In that way, breath analysis could allow a fast differential diagnosis as first line screening, optimizing COVID-19 management.