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.

New Paper Reveals Insights into Bacteria that Live on Your Skin and in Your Gut

What do MEBO (metabolic body odor), PATM ("People are Allergic to ME" condition) and TMAU (trimethylaminuria) have in common - beside the obvious:  airborne substances that make people feel uncomfortable?  New paper published in JMIR Dermatology - Cutaneous Bacteria in the Gut Microbiome as Biomarkers of Systemic Malodor and PATM Conditions - demonstrates: it's microorganisms that live on the skin and can be also present in the gut. The results of a clinical trial reported in this paper showed that the same microbes can modulate severity of odor or allergic reactions in others independently of genetics and trimethylamine metabolism. 

Researchers long suspected that there was a link between gut and skin health. Recent studies have confirmed it for a number of inflammatory skin diseases - such as psoriasis, rosacea, acne and atopic dermatitis. Microbes have been also suggested as targets for treating TMAU, a disorder that causes the body to constantly emit foul odor - from the skin, the mouth and the nose - via skin or fecal microbiome transplantation, antibiotics and probiotics. However, existing treatments are too broad, can lead to other health problems and lack understanding of precise targets and mechanisms. 

The paper shows that MEBO and PATM conditions don't always arise because of the decrease in microbial diversity. About half of the people might be lacking in microbial richness, but another half has too many different bacterial species to handle. 

The figure shows results of 22 study volunteers that were able to observe both flare-ups and improvements in their condition. The Y axis shows changes in microbial diversity vs abundances of selected bacterial species (X axis) for 12 female and 10 male participants. The arrows are labeled with 3 or 4 digits - the last digits of MEBO ID. Beginning of the arrow shows participants' microbial diversity and proportion of skin microbes in the gut during flare-ups, the end of the arrow points to improvements. As this figure shows, the only exceptions to the conclusion that the fewer cutaneous bacteria in the gut, the fewer skin emanations were 1214, 1287 and 1307. All of them observed very minor if not negligible (and easy to misinterpret) improvement of their condition (flare-ups happening from “all the time” to “most of the time”). 1214 was seen by a professional dermatologist, who concluded that a diagnosis of bromhidrosis didn’t seem warranted. 1307 had undergone a Botox procedure to treat hyperhidrosis, but was still experiencing symptoms (and, from our results, large fluctuations in odorous skin bacteria). 1287 did not report any skin odors and noted only halitosis. 

Read the paper to learn more and stay tuned for more details as they develop.

REFERENCE

Gabashvili IS  Cutaneous Bacteria in the Gut Microbiome as Biomarkers of Systemic Malodor and People Are Allergic to Me (PATM) Conditions: Insights From a Virtually Conducted Clinical Trial

JMIR Dermatol 2020;3(1):e10508

URL: https://derma.jmir.org/2020/1/e10508

DOI: 10.2196/10508

The Many Genes of TMAU

Twenty years ago Trimethylaminuria was linked to mutations in the FMO3 gene. It turns out there are many more genes that can lead to this condition. 

---------- READ MORE -------

The Smell of COVID-19

 From oatmeal cookies, rotting apples and burnt chocolate to bleach, gasoline and the smell of wet dog - all infections have a distinct odor signature. Is there a signature for COVID-19?

---------- READ MORE -------

Microbial diagnostics of MEBO

There are many medical conditions for which there are no standard tests for definite diagnosis and no established cures.  Diagnosing and curing Metabolic Body Odor (MEBO) is even more difficult. Especially because MEBO is an umbrella term for several different conditions.

---------- READ MORE -------

Gender - confounder of concern?

Background and clinical characteristics measured at baseline are comparable in the groups of our study. But this doesn't eliminate the need to investigate the impact of confounding. We've already analyzed the effects of age, What about gender as a potential confounder?

------------------  READ MORE ------------------------

Age and Metabolic Body Odor

MEBO is a complex condition and while some of the cases seem simpler, non-linear analysis approaches are better equipped to handle the task.  And this creates new challenges regarding  the existence of confounding factors.