Sunday, December 27, 2020

The Breathprint of COVID-19

Bad breath in those infected with COVID-19 might be the least of their problems. But studying it helps in understanding the mechanisms of this deadly respiratory disease and developing diagnostic tests. 

Dozens of confirmed cases of halitosis owing to active infection by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) have been reported in the literature (Patel & Woolley, 2020; Riad et al, 2020)

Possible explanations were decreased salivatory flow due to angiotensin‐converting enzyme 2 receptor-mediated alterations in the tongue, a greater risk of bad breath for mouth breathers who are also more prone to halitosis and increased attention to odor when wearing face masks. Another likely explanation is bacterial co‐infections arising from the novel coronavirus.

DNA analyses of microbial communities in the respiratory tract of those infected with SARS‐CoV‐2 frequently detect abnormally high bacterial reads of Prevotella, Streptococci, Treponema, Veillonella and Fusobacteria, known to emit malodorous volatile sulfur compounds and volatile fatty acids (VFAs). In addition to odor, VFAs could impair T- and B-cell proliferation responses and cytokine production.

What molecules could we expect to find in a person infected with the novel coronavirus? Lamote and colleagues review dozens of (often overlapping) molecules detected in other infections. Among those are aliphatic alcohols, branched hydrocarbons, alkane derivatives, terpenes, dimethyl sulfide and other sulfur and nitrogen-containing compounds. Three aldehydes (octanal, nonanal, and heptanal) drew special attention as candidate biomarkers in pediatric SARS-Cov-2 infection (Berna et al., 2020). These three biomarkers demonstrated 100% sensitivity and 66.6% specificity. Analysis of breath in two groups of adults with median ages 40 and 60 identified aldehydes (ethanal, octanal), ketones (acetone, butanone), and methanol that discriminated COVID-19 from other conditions. Aldehyde Heptanal had significant predictive power for severity of the disease.

It has been shown that properly trained dogs  are able to detect an olfactory signature of SARS-CoV-2 infection with a specificity greater than 90%. Several clinical trials have been initiated to study biomarkers of COVID-19 in breath by e-nose and other technologies. Two studies have been already completed and one paper reported successful detection using Aeronose (Wintjens et al, 2020) with 86% sensitivity and negative predictive value of 92%. Gas Chromatography-Ion Mobility Spectrometry allowed differentiation of patients with definite diagnosis of Covid-19 from non-Covid-19 with about 80% accuracy and 82.4%/75% to 90%/80% sensitivity/specificity. 


REFERENCES

Patel J, Woolley J. Necrotizing periodontal disease: Oral manifestation of COVID‐19. Oral diseases. 2020 Jun 7.

Riad A, Kassem I, Hockova B, Badrah M, Klugar M. Halitosis in COVID-19 patients. Special care in dentistry: official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry. 2020 Nov.29

Lamote K, Janssens E, Schillebeeckx E, Lapperre TS, De Winter BY, Van Meerbeeck JP. The scent of COVID-19: viral (semi-) volatiles as fast diagnostic biomarkers?. Journal of breath research. 2020 Jun 29.

Berna AZ, Akaho EH, Harris RM, Congdon M, Korn E, Neher S, Farrej MM, Burns J, John AO. Breath biomarkers of pediatric SARS-CoV-2 infection: a pilot study. medRxiv. 2020 Dec. 7

Ruszkiewicz DM, Sanders D, O'Brien R, Hempel F, Reed MJ, Riepe AC, Bailie K, Brodrick E, Darnley K, Ellerkmann R, Mueller O. Diagnosis of COVID-19 by analysis of breath with gas chromatography-ion mobility spectrometry-a feasibility study. EClinicalMedicine. 2020 Oct 24:100609.

Wintjens AG, Hintzen KF, Engelen SM, Lubbers T, Savelkoul PH, Wesseling G, van der Palen JA, Bouvy ND. Applying the electronic nose for pre-operative SARS-CoV-2 screening. Surgical endoscopy. 2020 Dec 2:1-8.