Pan-Anosmia

Mechanism behind loss of smell with COVID-19 revealed

Feb 2022, phys.org

https://medicalxpress.com/news/2022-02-mechanism-loss-covid-revealed.html

• For more than 12 percent of COVID-19 patients, olfactory dysfunction persists 
• SARS-CoV-2, indirectly dials down the action of olfactory receptors
• The new study may also shed light on the effects of COVID-19 on other types of brain cells, and on other lingering neurological effects of COVID-19 like "brain fog," headaches, and depression
• Presence of the virus near nerve cells in olfactory tissue brought an inrushing of immune cells, microglia, T cells, and cytokines that changed the genetic activity of olfactory nerve cells
• They used infected golden hamsters and olfactory tissue from 23 human autopsies [hamsters are more susceptible to nasal cavity infections]

Reminder of why it's such a big deal when you start messing with smell:

"Other work posted by these authors suggests that olfactory neurons are wired into sensitive brain regions, and that ongoing immune cell reactions in the nasal cavity could influence emotions, and the ability to think clearly (cognition), consistent with long COVID."

The talk on gene behavior and downregulation of receptor building is lost on me (not a geneticist, not a neurologist), but one of the main points I am reminded of when reading this is -- for those who experienced a change in taste or smell, for any reason, but especially after a COVID infection, long-term brain damage is possibly ongoing, but it's the kind to go undetected for another 20-30 years, depending on how old you are, of course. 

They also seem to suggest that this is an explanation for why people experience brain fog, and even emotional disturbance, all of which makes a lot of sense, because your sense of smell is connected to the all those brain areas -- the hippocampus for memory and the amygdala for emotion, both integral parts of the limbic system. 

via NYU Langone Health Department of Microbiology, NYU Grossman School of Medicine and Columbia University: Marianna Zazhytska et al, Non-cell autonomous disruption of nuclear architecture as a potential cause of COVID-19 induced anosmia, Cell (2022). DOI: 10.1016/j.cell.2022.01.024

http://dx.doi.org/10.1016/j.cell.2022.01.024

WHERE CAN I GET MORE INFORMATION ON SMELL LOSS?

Monell Anosmia Project - US Organization studying smell and taste

https://monell.org/anosmia/

AbScent - UK Organization raising public awareness of smell loss

https://abscent.org

National Institute on Deafness and Other Communicable Disorders (NIDC) - Smell Disorders

https://www.nidcd.nih.gov/health/smell-disorders

ENT UK - Loss of Smell as Marker of Covid-19 Infection

https://www.entuk.org/sites/default/files/files/Loss%20of%20sense%20of%20smell%20as%20marker%20of%20COVID.pdf

Post Script:

• How Covid-19 can damage the brain - BBC Future, June 2020. https://www.bbc.com/future/article/20200622-the-long-term-effects-of-covid-19-infection
• Trying to Make Sense of Long COVID Syndrome, Dr. Francis Collins. NIH Director's Blog, January 19th, 2021. https://directorsblog.nih.gov/
• What Makes a Better Smeller? Asifa Majid, Laura Speed, Ilja Croijmans, et al. Sage Pub., Jan 2017, volume 46 issue pp 406-430. https://doi.org/10.1177/0301006616688224
• Monell Center Scientists Find that Insulin is Necessary for Repairing Olfactory Neurons: Findings Point to Possible Treatment for Smell Loss, May 2021. https://monell.org/monell-center-scientists-find-that-insulin-is-necessary-for-repairing-olfactory-neurons-findings-point-to-possible-treatment-for-smell-loss/
• via Children's Hospital Boston: Laura Montefusco et al, Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection, Nature Metabolism (2021). DOI: 10.1038/s42255-021-00407-6. http://dx.doi.org/10.1038/s42255-021-00407-6

Healthy Brains

An interest in olfaction has me following the anosmic effects of this disease. A career as an industrial hygienist has me posting public health information on this olfactory awareness weblog:

Our sense of smell is a secret weapon in the fight against the 2019 novel coronavirus.

1. Loss of smell (anosmia) is a primary symptom of Covid-19.
2. Covid-19 may cause neurological damage.
3. This is not a coincidence.

Most people don't realize it but your sense of smell offers very sensitive diagnostics for complex brain activity, like how it can predict Alzheimer's decades in advance. This is because our sense of smell has special connections with the brain that other senses don't have. This also gives us an opportunity to monitor our own "brain health," and that's the main reason I'm sending this.

I'll let this recent BBC article on the topic fill-in the details; it's not long:
How Covid-19 can damage the brain - BBC Future

SEE UPDATE (7/25) ON NEW INFORMATION FROM HARVARD SPH BELOW

If you don't read that article, and if you're about to stop reading this, please:

• Pay attention to changes in smell or taste, both for you and those around you.

• Changes in smell and taste are a primary symptom for Covid-19.

• Changes in smell and taste, in general and aside from a Covid infection, could be a sign of neurological issues and may warrant attention from a professional.

• The sooner you recognize neurological issues the better.

WHERE CAN I GET MORE INFORMATION?

Monell Anosmia Project - US Organization studying smell and taste

https://monell.org/anosmia/

AbScent - UK Organization raising public awareness of smell loss
https://abscent.org

National Institute on Deafness and Other Communicable Disorders (NIDC) - Smell Disorders
https://www.nidcd.nih.gov/health/smell-disorders

ENT UK - Loss of Smell as Marker of Covid-19 Infection
https://www.entuk.org/sites/default/files/files/Loss%20of%20sense%20of%20smell%20as%20marker%20of%20COVID.pdf

[x] image source link

Post Script:
The ability to detect smells predicts recovery and long-term survival in patients who have suffered severe brain injury, a new study has found. A simple, inexpensive 'sniff test' could help doctors to accurately diagnose and determine treatment plans for patients with disorders of consciousness.

Published in the journal Nature, ...

Simple sniff test reliably predicts recovery of severely brain injured patients
May 2020, phys.org
https://medicalxpress.com/news/2020-04-simple-reliably-recovery-severely-brain.html

Olfactory sniffing signals consciousness in unresponsive patients with brain injuries, Nature (2020). DOI: 10.1038/s41586-020-2245-5 , www.nature.com/articles/s41586-020-2245-5

UPDATE ON NEW INFORMATION

Eric Song et al. Neuroinvasion of SARS-CoV-2 in human and mouse brain, Journal of Experimental Medicine (2021). DOI: 10.1084/jem.20202135

David H. Brann et al. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia, Science Advances (2020). DOI: 10.1126/sciadv.abc5801

Trying to Make Sense of Long COVID Syndrome, Dr. Francis Collins. NIH Director's Blog, January 19th, 2021. https://directorsblog.nih.gov/

Harvard Medical School, coming with all the hot smell data these days, figures out what's going on with the covid smell loss problem.

I'm pretty sure you already know this, but just in case -- covid-19 can cause changes in smell or taste. It's a primary symptom, and the number one symptom for identifying infection (also the earliest; others may not show up until days later). The problem is that most people don't even know they have a sense of smell in the first place, so they don't notice that it's missing.

We thought it was the actual neurons themselves getting attacked and damaged by the virus. This is certainly possible, because your olfactory neurons, which are like little brain fingers with special neuron cells at the very tips, and are the only part of your brain that reach across the blood-brain barrier, outside the body envelope, and into the world. 

Imagine a piece of your brain reaching, creeping, crawling outside your skull to sniff the world firsthand. That's your olfactory neurons. That's where they stick the swab when taking your covid test sample. Sounds pretty vulnerable. I can see the line of reasoning here.

Well we were wrong (and when I say we, I mean them, because I'm not a scientist). It's not the neurons themselves being attacked, but their "supporting cells." These nonneuronal cells are described as sustentacular cells which wrap around the neurons for structural and metabolic support, and also basal cells which are regenerative stem cells responding to damage.

The thing is, I'm not sure of the implications here. Do we actually know what causes non-obstructive virus-induced anosmia prior to this? And what are the associations between people who have it and people who later develop neurodegenerative symptoms like Alzheimer's etc.? I don't think the new information from this study lets us put our guard down. Using the precautionary principle, I would say that your sense of smell is deeply connected to core areas of your brain, and any dysfunction there should prompt you to investigate potential neurological damage. With the brain, as plastic as it is, and important to quality of life, anything out of the ordinary should be taken seriously, and as quickly as possible. 

Notes:

David H. Brann et al. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia, Science Advances (2020). DOI: 10.1126/sciadv.abc5801

https://www.biorxiv.org/content/10.1101/2020.03.25.009084v2

This lab also just released one of the more groundbreaking reports on how olfaction works,  basically in the same week: Stan L. Pashkovski et al, Structure and flexibility in cortical representations of odor space, Nature (2020). DOI: 10.1038/s41586-020-2451-1

http://dx.doi.org/10.1038/s41586-020-2451-1

Local Odor Vocab

Curren's SCAQMD Urban Odor Dictionary

link to google fusion graph

You’re looking at a smell network based on the work of UCLA post-grad named Jane Curren. She took all the words used in odor complaints in southern California, and found the source of those complaints. These odor sources can be anything from a hidden garbage dump to a local restaurant. The size of the blue nodes doesn’t indicate smelliness; it indicates more descriptors. Restaurants have more descriptors because they have 1. More people near them and 2. A greater diversity of things that smell. (I’m guessing this.) What this chart does show is the most common odor complaints in the middle of the cluster – we smell burnt things a lot. Also rotten eggs/sulfur/natural gas.

Below, Curren went further and found the specific chemical source of these smells, and I listed them below. Next time you smell something funny, check this list. (And the next time you’re in New Jersey, take a tour of the New Jersey Turnpike mobile museum of olfactory delights, you’ll smell firsthand many of the odors on this list!)

Curren's Urban Odor Lexicon

               

Descriptor                           Odorant

solvent                                 2-butanone

petroleum                          2-methyl-1-propene

pungent                               2-pentanone

sweet                                   2-pentanone

lemon                                   acetaldehyde

alcohol                                  acetaldehyde

acrid                                      acrolein

pungent                               ammonia

sweet solvent                   benzene

sweet                                   dichloromethane

decayed cabbage             ethyl mercaptan

pungent                               formaldehyde

rotten egg                           hydrogen sulfide

woody                                  m-cresol

resinous                               m-cresol

medical                                                m-cresol

woody                                  o-cresol

resinous                               o-cresol

medical                                                o-cresol

woody                                  p-cresol

resinous                               p-cresol

medical                                                p-cresol

medical                                                phenol

sweet                                   phenol

irritating                               propanal

fruity                                     propanal

empyreumatic                  pyridinec

irritating                               sulfurdioxide

aromatic                              toluenec

fishy                                      trimethylamine

pungent                               trimethylamine

sweet                                   acetone

minty                                    acetone

sweet solvent                   benzene

woody                                  cresol

resinous                               cresol

medicinal                             cresol

sour                                       dimethyl disulfide

onion                                    dimethyl disulfide

decayed cabbage             dimethyl sulfide

decayed cabbage             ethyl mercaptan

garlic                                      ethyl mercaptan

aromatic                              ethylbenzene

pungent                               formaldehyde

rotten eggs                         hydrogen sulfide

skunk                                    i-propyl mercaptan

sour                                       methyl mercaptan

garlic                                      methyl mercaptan

decayed cabbage             methyl mercaptan

skunk                                    n-butyl mercaptan

skunk                                    n-propyl mercaptan

medicinal                             phenol

sweet                                   phenol

irritating                               propanal

sweet                                   p-xylene

sharp                                     thiophene

skunk                                    thiophene

rubber                                  toluene

moth balls                           toluene

aromatic                              1,2,4-trimethylbenzene

aromatic                              1,3,5-trimethylbenzene

vinegar                                 acetic acid

sour                                       acetic acid

chemical                              acetone

sweet                                   acetone

acrid                                      acrolien

pungent                               ammonia

sweet                                   a-pinene

pine                                       a-pinene

sweet solvent                   benzene

malty                                     butanal

burnt                                     butanal

rancid                                    butyric acid

sour                                       butyric acid

perspiration                       butyric acid

fruity                                     butyl acetate

dead body                          cadaverine

disagreeable sweet        carbon disulfide

almond                                 chlorobenzene

sweet                                   chloroform

ethereal                               chloroform

pungent                               crotonaledehyde

gasoline                               decane

ethereal                               dichloromethane

sour                                       dimethyl disulfide

onion                                    dimethyl disulfide

decaying vegetation       dimethyl sulfide

aromatic                              ethylbenzene

oily                                         heptanal

musty                                   heptanal

woody                                  heptanal

fatty                                      hexanal

green                                    hexanal

rotten egg                           hydrogen sulfide

sharp                                     isopropyl benzene

aromatic                              isopropyl benzene

sharp                                     cumene

aromatic                              cumene

lemon                                   limonene

decayed cabbage             methyl mercaptan

moth balls                           naphthalene

tar                                          naphthalene

sweet                                   m-xylene

gasoline                               octane

sweet                                   o-xylene

pungent                               pentanal

sharp                                     propanal

vinegar                                 propanoic acid

sour                                       propanoic acid

sweet                                   p-xylene

solvent                                 styrene

rubber                                  styrene

sweet                                   tetrachloroethene

rubber                                  toluene

moth balls                           toluene

sweet                                   tricholoroethane

fishy                                      trimethylamine

fecal                                      valeric acid

sour                                       valeric acid

sweet                                   vinyl acetate

Suffet and Rosenfeld's Urban Odor Lexicon

*much of Curren’s work came from Suffet and Rosenfeld, so I added their leftover terms here

Descriptor                           Odorant

Coffee                                  Furfruryl Thiopropionate

earthy                                   Geosmin

musty                                   2-Methyl isoborneol

moldy                                   2,4,6-Trichloroanisole

grassy                                   Cis-3-hexen-1-ol

dead animal                       Putresine

rotten vegetable              Dimethyl Trisulfide

fishy                                      Dimethyl Amine

fishy                                      Methyl Amine

plastic                                   Methyl Methacrylate

fecal                                      Indole

manure                                  Skatole

burnt                                     Guiaicol

Primary document: Curren, J. 2012. Characterization of Odor Nuisance. UCLA.

http://www.wcsawma.org/wp-content/uploads/2012/11/JMC-dissertation.pdf

Supporting document: Suffet, I.H., and P.E. Rosenfeld (2007). The Anatomy of Odour Wheels for Odors of Drinking Water, Wastewater, Compost and the Urban Environment, Water Science and Technology 55(5), 335-344.

Research note: The descriptor names come from the above source and supporting documents, whereas the odor causing compounds were matched against varying sources which will not be listed here; see instead the source document for those references

Constructing an Urban Smell Map

Must be something in the air. Over the past few years, many artists/scientists have been making smell maps of their cities. Victoria Henshaw is the most popular, with her “smellwalks” and her book Urban Smellscapes. But there’s others, like Kate McLean’s Sensory Maps, and Jason Logan’s handscrawled Scents and the City (seen above).

I think it’s just that maps are becoming a big deal. Something about big data, social media, and GIS interface. Maybe that Snapchat debacle too. The smell map we’re looking at today wraps up all three of these, and makes a very ambitious project into a neat interactive plaything. I wasn’t satisfied with the map, however, and was way more interested in the Urban Smell Dictionary they created in order to make their map I the first place. I was suspicious, so I went through their full report.

So here goes:

First they conducted smellwalks in each of the cities to be mapped (London and Barcelona), and along with some previous literature on the subject, they used the words generated on these smellwalks to support their lexicon. Then they collected geo-referenced picture tags from Flickr (530K), Instagram (35K), and Twitter (113K). Those tags and tweets were matched with the words in the smell dictionary, and voila!

The lexicon, in detail:

First they did some co-occurrence modeling, so that smell-words that appear in the same post/tweet are related. Then they used network analysis software, also called a community structure detection algorithm. InfoMap is the one they used, but they did further partitioning with another program.

The result?

Urban Smellscape Aroma Wheel

Who did it?

University of Turin computer science professor Rossano Schifanella, and Bell Labs researchers Luca Maria Aiello and Daniele Quercia.

Image source: “I Smell NY” Smell Map by Jason Logan

Notes:

Quercia, Daniele, Rossano Schifanella, Luca Maria Aiello, and Kate McLean. 2015. “Smelly Maps: The Digital Life of Urban Smellscapes.” In Proceedings of the Ninth International AAAI Conference on Web and Social Media (ICWSM 2015). Palo Alto, CA: AAAI Publications. 327-336. Accessed November 28, 2016.

http://www.aaai.org/ocs/index.php/ICWSM/ICWSM15/paper/view/10572

Full pdf:

https://www.aaai.org/ocs/index.php/ICWSM/ICWSM15/paper/view/10572/10516

Post Script:

There was a really cool observation made during their report which I’d like to explain here. In the remarks they make about “base notes,” there's some good entropy data in there somewhere, about smells, awareness, and the amount of time you spend in a place/some measure of odor-attenuation.

Let's start with their explanation of "notes" (and I’ll just quote from the paper)

“When a new perfume is created, different top, middle, and base note ingredients are combined to make the new fragrance. Those notes differ in terms of their tenacity. Top notes are those perceived immediately (e.g., citrus fruits, aromatic herbs) and, since they are intense, they are also volatile and evaporate quickly. By contrast, base notes are those adding depth and stay on the skin for hours (e.g., wood, moss, amber, and vanilla). Middle notes sit somewhere in between (e.g., flowers, spices, berries).”

Now they explain the urban smellscape:

“Base notes. The macro-level base notes for the urban smellscape are those that are likely smelled by a city’s first-timer visitors. That is because known odors are unconsciously processed by people, while only unfamiliar or strong odors are brought to people’s attention (as potential threats or sources of pleasure). As a result, residents are not likely to pay attention to their city’s base notes, while visitors would be able to consciously process them.

“Mid-level notes. As one moves through the city, the base notes blend with dominant smells that are localized in specific areas (e.g., factories, fish markets).

“High notes. Finally, the micro-level high notes are shortlived odors (e.g., goods from a leather shop). These are emitted in points that are very localized in space and time. … High notes are likely to go undetected because of data sparsity and because of our spatial unit of analysis being a street segment.”

And one more thing, I’m like how do you say this and not cite it??

 “Air pollutants also have been found to reduce the ability of floral scent trails to travel through air.”

-I’ve never heard this, and they provide no citation