## 4 Discussion
### Limitations and Future Perspective  
Due to the wide performance range of the antigen tests currently on the market, there remains a fair possibility that the three individuals tested by an antigen test alone were not accurately accounted for (positive or negative). While the PCR test is the current gold standard for SARS-CoV-2 detection and diagnostics, it is an imperfect tool as well. As with most diagnostic tools, it is important to acknowledge the possibility of false positive and false negative results produced by PCR tests. Additionally, the tests are bound to their own detection limitations. Participants who tested as \"negative\" using a PCR test may have attained this result due to a low viral load or stage of infection as opposed to a \"truly negative\" SARS-CoV-2 infection status.  
In addition to concerns over ground truth SARS-CoV-2-infected patient status, there are concerns over previous contractions of SARS-CoV-2 and the possibility that patients were afflicted by long-COVID at the time of sample collection. Recent work in the field of biomedical scent detection has suggested that canines trained to detect SARS-CoV-2-infected positive samples may also be able to detect long-COVID, which is the persistent effects of COVID-19 that remain beyond PCR test positivity (post-COVID affiction) [41]. These new findings suggest that there is more similarity between long-COVID odor presentation and SARS-CoV-2-positive odor presentation than there is between long-COVID and SARS-CoV-2-negative presentations. Due to the difficulty in properly determining previous SARS-CoV-2 infection (individuals may have been asymptomatic or have gone untested during a period of illness), the researchers did not actively seek to identify and remove individuals who may have been suffering from long-COVID. This consideration is viewed as a reasonable approximation of the real-world application of this work, as patients would be subject to SARS-CoV-2 screening regardless of long-COVID status.  
The authors intend to continue their investigation of the VOC expression of SARS-CoV-2 infection as it relates to human hand odor. This work served as an initial investigation of the probative value of human hand odor as a medium for SARS-CoV-2 infection status determination. The authors intend to continue this discussion in a secondary manuscript wherein the influence of the suspected SARS-CoV-2 variant is evaluated as a factor driving class separation. Additionally, the separability of SARS-CoV-2 variants will be examined.  
The presented methodology of using human hand odor as a potential diagnostic medium is a promising prospect for an adaptive field-deployable technology. While the authors note that the infrastructure does not currently exist for the wide application of this technology, they believe that human hand odor analysis is a viable diagnostic medium that has the capacity to be expanded upon and adapted into a fieldable methodology. The greatest benefit of this technology would reside in mass-screening venues such as airports or other readily visited areas with elevated concerns of transmission. This begins with the adoption of portable GC-MS instrumentation, allowing for lower-cost installations. This methodology could also open a pathway for the continual improvement of the technology through the periodic introduction of new SARS-CoV-2-positive and -negative samples (verified by PCR testing). As status is confirmed, more samples can be added to the model, allowing for continual training; as SARS-CoV-2 variants evolve, so will the model. The adoption of a machine learning-backed approach provides a route to teaching and improving diagnostic models at a rate that is competitive regarding the continual evolution of our targeted virus.