Viruses and Vaccines

The COVID-19 Back-to-normal study was initiated in January 2021 as an effort of a tight-​knit neighborhood to help each other avoid the virus and vaccinate safely.

Later the research protocol was approved by MEBO Research IRB and the study was open to other communities around the world. 

By now, we have over 600 participants. 

Early results of the study in MEBO/PATM community, based on the replies of the first 26 enrollees, showed that while reactions to vaccine were similar to the general population, experiences with COVID-19 infections were not - 2 individuals were not able to avoid the disease in this group, and both of them experienced long term effects. 

As of today, we have stories from 41 members of MEBO/PATM community and 6 different vaccines: AstraZeneca-Oxford, Johnson & Johnson’s single-shot, Moderna, Pfizer-BioNTech, Sinovac Biotech’s CoronaVac and BBIBP-CorV, also known as the Sinopharm vaccine.

Currently, in various areas of the world, 19 COVID-19 vaccines have been authorized for use. Statistics on short-term effects of these vaccines have been published for different groups. If we compare our data to published data matching by ages and vaccines, short-term effects are very similar. Some of our sub-groups, especially healthy elderly participants, experienced far fewer side effects than reported in the literature. There were slightly fewer common adverse reactions in MEBO Pfizer group, but incidences of fatigue were on a higher side for all vaccines, and there were more reports of fever experienced after Moderna and Astrazeneca, albeit it was not significantly different from the general population. More significant differences were for less common and longer-term effects including fast heartbeat, dry mouth, skin reactions and swollen lymph nodes. The figure below shows common symptoms for Long COVID. Underlined are some of the issues reported after COVID vaccine uptakes in the group. Possible worsening of MEBO/PATM symptoms after vaccinations was reported by 10% of study participants. 

The most significant difference of MEBO group from the general population is the response to COVID-19 infection. 6 people (3 males, 3 females) out of 41 study participants experienced COVID-19 and all of them had long-term reactions. 5 out of 6 considered themselves long-haulers. The 6th person reported persistent MEBO/PATM issues  post-acute COVID-19. That's 80-100% of long-haulers, ~4 times more than researchers estimate! Our rate is closer to some groups with severe genetic conditions - such as individuals with hypohidrotic ectodermal dysplasia  - predisposing to bad smell from nostrils. 

Postinfectious fatigue was the most commonly reported symptom in this group. Long-lasting loss of smell happened in ~16% - as in the general population. MEBO/PATM symptoms were significantly increased, unless well under control before the infection. There's anecdotal evidence, based on posts in social media, that some sufferers of chronic COVID-19 are experiencing more aversive underarm smell. 7% of long-haulers are thought to sense phantom distorted smells. Is it really imagined smells or could it be real change in their odor?

We also had reports of successful management of persistent COVID symptoms with a low histamine, gluten-free, dairy-free and no carb diets.

Why is MEBO/PATM community more susceptible to long COVID? A new study argues that long-haulers might actually be experiencing an attack of fatigue-inducing Epstein-Barr virus (EBV, a member of herpesvirus family HHV-4) that was lying dormant in their bodies.  For this study, Gold and his colleagues analyzed blood of 30 people with chronic COVID (out of 185 COVID survivors). 20 out of these 30 carried high levels of EBV antibodies. Vaccines were shown to reactivate viruses too, in much rarer cases. As was demonstrated for Pfizer vaccine that woke up another herpes virus, chickenpox herpes-zoster (HHV-3), that causes shingles when reactivated (this happened to 1% of patients with autoimmune inflammatory rheumatic diseases). Herpes simplex (HSV-1) can be also kept in remission by a healthy immune system and can be also reactivated by COVID-19.

MEBO and PATM symptoms could arise following an infection. Perhaps SARS-CoV-2 can reactivate the old viruses that caused these symptoms to begin with? 

Community immunity (also known as herd immunity) protects everyone. We hope that MEBO/PATM community stays COVID-free and safe. 

REFERENCES

Gabashvili IS. Community-Based Phenotypic Study of Safety, Tolerability, Reactogenicity and Immunogenicity of Emergency-Use-Authorized Vaccines Against COVID-19 and Viral Shedding Potential of Post-Vaccination Infections: Protocol for a prospective study medRxiv 2021.06.28.21256779; doi: https://doi.org/10.1101/2021.06.28.21256779

McDonald I, Murray SM, Reynolds CJ, Altmann DM, Boyton RJ. Comparative systematic review and meta-analysis of reactogenicity, immunogenicity and efficacy of vaccines against SARS-CoV-2. npj Vaccines. 2021 May 13;6(1):1-4.

Gold JE, Okyay RA, Licht WE, Hurley DJ. Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation. Pathogens. 2021 Jun;10(6):763.

COVID-19 and vaccine reactogenicity in MEBO/PATM community

Infections have been shown to alter body odor and so have immunizations. So far, only nonhuman animals were able to detect the subtle changes in chemical makeup after vaccinations and even their sensitive noses were not able to differentiate between different vaccines - such as the rabies virus or the West Nile virus vaccines [Kimball et al, 2014]. However, this was the case of very mild reactions to immunization. Even slightly stronger inflammatory responses, to relatively weak immune challenges, can, indeed, be detected by human noses [Gordon et al, 2018]. Urine and axillary odor are becoming slightly more aversive in healthy humans, as a function of immune activation. But this is not supposed to last too long.

Our preliminary results, based on responses to the survey for 24 members of MEBO community and 6 of their family members show a wide variety of reactions to Astrazeneca, J&J, Moderna, Pfizer and Sinovac/Coronavac vaccines. 

Interestingly, Pfizer vaccine that caused no or very mild reactions in several MEBO participants, was also the vaccine that possibly caused temporary worsening of odor symptoms in one person in the community. Another MEBO participant that reported possible worsening of odor from Moderna vaccine had one thing in common with the other individual - they both had pre-existing conditions related to their upper digestive tract. Some Astrazeneca recipients also reported odor issues but did not think it was worse than usual. 

One of the most interesting observations was that even though only 2 members of MEBO/PATM community reported COVID-19 infection (before or between vaccinations), both of them had long COVID with long-term neurological manifestations such as fatigue, ENT symptoms and loss of smell.

Adverse reactions to COVID-19 vaccines are influenced by a multitude of factors, many of which can be anticipated and alleviated. A certain level of inflammation is needed to trigger an effective adaptive immune response, but both environment and genetic makeup determine who is more likely to experience particular symptoms after infection and from the vaccine.

You can help by telling us about your experiences with COVID-19 and/or vaccinations. These surveys can be used for posting your brief stories - no need to answer all the questions. And you can always add to your story later. Please use your anonymous ID and let us know if you have any questions.

Survey

in English:  https://bit.ly/BTN-eng

en Español: https:/bit.ly/BTN-esp

We'll be posting more observations and comparisons with over 600 participants of our study from other communities. 

REFERENCES

Blumental S, Debré P. Challenges and issues of anti-SARS-CoV-2 vaccines. Frontiers in Medicine. 2021;8.

Gordon AR, Kimball BA, Sorjonen K, Karshikoff B, Axelsson J, Lekander M, Lundström JN, Olsson MJ. Detection of inflammation via volatile cues in human urine. Chemical senses. 2018 Nov 1;43(9):711-9.

Kimball BA, Opiekun M, Yamazaki K, Beauchamp GK. Immunization alters body odor. Physiology & behavior. 2014 Apr 10;128:80-5.

Vaccine to cure body odor?

There could be a vaccine for everything. Scientists are working on personal vaccines, vaccines reducing body weight or narcotic dependence, vaccines for just about anything.  Can there be a vaccine improving body odor? Certainly, and it could target not only bacteria (in body crevices) worsening odor, but also molecules responsible for odor. This would be a very complex task, however, as there is still a lot we don't understand.  For example, if metabolism and microbiomes leading to body odor cause similar reactions to already existing vaccines. 

Several vaccines to prevent COVID-19 were authorized for emergency use and hundreds of millions doses have been administered. 2 millions of vaccinated individuals in the US completed a health survey in the 7 days following their vaccination via the v-safe app.

This table shows top adverse reactions reported to the first two vaccines authorized in the US. Hundreds of social media groups on Facebook, reddit and WhatsApp are also flooded by descriptions of adverse reactions and immunity related events. What is missing? The ability to systematically analyze all these reactions in different health and neighborhood communities.

We started such a study in one neighborhood community and would like to also conduct it in the MEBO/PATM communities. We are also opening it to MEBO friends and family - asking them to indicate their relationship with MEBO/PATM in the comment section of the survey.

We are also collecting COVID-19 experiences in different groups of people, analyzing infectious disease susceptibility risks. 

in English: https://bit.ly/BTN-eng

en Español: https:/bit.ly/BTN-esp

Thank you for your help!

REFERENCES

ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2021 April 6 - . Identifier NCT04832932, The COVID-19 Back-to-Normal Study [cited 2021 April 7]; Available from: https://clinicaltrials.gov/ct2/show/NCT04832932

Chapin-Bardales J, Gee J, Myers T. Reactogenicity Following Receipt of mRNA-Based COVID-19 Vaccines. JAMA. 2021 Apr 5. doi: 10.1001/jama.2021.5374. Epub ahead of print. PMID: 33818592. 

Zimmermann P, Curtis N. Factors that influence the immune response to vaccination. Clinical microbiology reviews. 2019 Mar 20;32(2). 

Mosquera MJ, Kim S, Zhou H, Jing TT, Luna M, Guss JD, Reddy P, Lai K, Leifer CA, Brito IL, Hernandez CJ. Immunomodulatory nanogels overcome restricted immunity in a murine model of gut microbiome–mediated metabolic syndrome. Science advances. 2019 Mar 1;5(3):eaav9788.

Bandaru P, Rajkumar H, Nappanveettil G. The impact of obesity on immune response to infection and vaccine: an insight into plausible mechanisms. Endocrinol Metab Synd. 2013;2(2):1000113-22. 

Kim YH, Kim JK, Kim DJ, Nam JH, Shim SM, Choi YK, Lee CH, Poo H. Diet-induced obesity dramatically reduces the efficacy of a 2009 pandemic H1N1 vaccine in a mouse model. Journal of Infectious Diseases. 2012 Jan 15;205(2):244-51. 

 Monteiro MP. Obesity vaccines. Hum Vaccin Immunother. 2014;10(4):887-95. doi: 10.4161/hv.27537. Epub 2013 Dec 23. PMID: 24365968; PMCID: PMC4896563. 

Ozgen MH, Blume S. The continuing search for an addiction vaccine. Vaccine. 2019 Aug 23;37(36):5485-90. 

Daniel W, Nivet M, Warner J, Podolsky DK. Early evidence of the effect of SARS-CoV-2 vaccine at one medical center. New England Journal of Medicine. 2021 Mar 23.

Rebuild your Health

There is increasing evidence that intestinal microbial dysbiosis has a role in the pathogenesis of systemic malodor conditions and other metabolic disorders. The most studied non-syndromic malodor condition Trimethylaminuria is usually inherited in an autosomal recessive fashion, which means that two mutations from both parents, both affecting abilities of FMO3 enzyme to catalyze the N-oxidation of trimethylamine into trimethylamine (eg, [Glu158Lys (rs2266782) and Glu308Gly (rs2266780)]), may be needed for a person to have symptoms. Yet genotype is not always predictive of phenotype, not even in this case.

Illustration by Monica Garwood

Studies have shown that the symptoms of metabolic inefficiencies, food intolerance and even allergies can be relieved by changing the composition of intestinal microbes and adjusting dietary components feeding these microbes - to encourage growth of microorganisms properly digesting problem ingredients. Lactose-digesting bacteria Lactobacillus acidophilus, Lactobacillus bulgaricus and Streptococcus thermophilus, for example, can help to digest lactose into useful compounds, instead of offensive gas. On the other hand, the low-FODMAP diet reduces gastrointestinal symptoms by reducing the food that bacteria ferment. For lactose-intolerance, however,  the "O" in FODMAPs - oligosacharides - can be beneficial as Galacto-oligosaccharides (GOS) are useful prebiotics promoting the growth of the right microorganisms. 

Rebuilding the network of microorganisms on and inside our bodies can help to improve the volatiles in the surrounding air, aka body and breath odor. Microbes associated with unpleasant odors include Anaerococcus, Corynebacterium, Campylobacter, and Propionibacterium [1], Gardnerella, Alloprevotella, Sutterella, and species of Candida. Microbes associated with improvements in odors include archaebiotic Methanomassiliicoccus luminyensis, Lactobacillus pentosus KCA1, and Lactobacillus salivarius, but there are more, working together and relying on each other. Our studies (see protocols of microbiome [2] and volatilome [3] trials published on Medrxiv)  identified several microbial strains and volatile compounds associated with improvement of malodor symptoms. We are currently summarizing our results and plan to publish it. Development of personalized protocols and defining the right compositions of probiotics and prebiotics is a long-term research endeavor. Meanwhile, be your own best medical researcher and take control of your wellbeing: 

Step 1: Pull out your fitness journal and create an action plan

• Analyze your diet, everyday activities, exercise and sleep patterns to make initial guesses about things that could be triggering your flareups or making you feel better. Write out a list of these things. 
• Break your goal into small steps and milestones. For example: if you have fructose as a potential trigger on your list, go fructose free for a week. An earlier survey of about 100 body odor and halitosis sufferers indicated stress (34%), food (25%) and environment, including the weather and perfumed products (15%) as main triggers of odors or PATM. Make sure you are not missing something in your diet - like Zinc, Vitamin C, or Vitamin D - insufficient amounts of these vitamins and minerals could also contribute to PATM. 
• Develop metrics for evaluating progress. Some people can't objectively evaluate their malodor or PATM condition. Try to find a trust buddy or take note of how the people around you react when you’re in close proximity. For example, pay attention to the space people leave between you and themselves (assuming COVID-19 is behind us and the 6-feet rule no longer applies!)

Step 2: Change your diet, physical activity and behavior

• Intestinal lining is regenerating every five to seven days, so you need to stick to your diet for at least a week to notice improvements in your symptoms. Most elimination diets are actually recommended for about 3–6 weeks, to allow the antibodies (negatively reacting to problem food components) dissipate. So if your diet seems to be helping, extend it to 3 or 6 weeks. 
• If it is not helping, try the next thing on your list. It should not be just diet - one study showed that bad breath was associated with abnormal sleep patterns. Perhaps you need to reevaluate your clothing material, temperature an humidity or mycotoxins in the environment? Are you getting enough sunlight ? Does your home have a healthy microbiome? Try to eliminate the triggers one at a time. No need to reduce your overall food intake, many people observe malodor or PATM flareups when they are hungry & undernourished. Try to train your body to digest more fiber - but start adding them to your diet little at a time, on weekends when you can safely experiment.   

Step 3: Let go of past hurts

• Stop dwelling on the past. You have the power to change your future. Learn how to express confidence with your body language. Pretend you are comfortable in presence of other people and they will learn to be comfortable in yours. 

RFRERENCES

1. 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 Dermatology. 2020 Nov 4;3(1):e10508.

2. Gabashvili I.S. Dynamics of the Gut Microbiota in MEBO and PATM conditions: Protocol of a fully remote clinical study. medRxiv. 2020 Aug.24. medRxiv 2020.08.21.20179242; doi: https://doi.org/10.1101/2020.08.21.20179242

3. Gabashvili I.S. Effects of diet, activities, environmental exposures and trimethylamine metabolism on alveolar breath compounds: protocol for a retrospective case-cohort observational study medRxiv 2021, Jan. 26 2021.01.25.21250101; doi: https://doi.org/10.1101/2021.01.25.21250101

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. 

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