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

Diabetes x Anosmia

Interesting theme here; anosmia, insulin and Covid:

It appears that long-Covid has more to do with the pancreas and insulin regulation than we thought, and this has implications for the health of our olfactory receptors.

Research from the Monell Center found that insulin may be able to treat smell loss:

1. Insulin plays a critical role in the maturation, after injury, of immature olfactory sensory neurons (OSNs). 

2. The research team induced diabetes type 1 in mice to reduce levels of circulating insulin reaching the OSNs. The reduced insulin interfered with the regeneration of OSNs, resulting in an impaired sense of smell. 

3. In addition, the team injured OSNs, which have a unique ability to regenerate in mammals. This approach allowed the investigators to ask whether OSNs required insulin to regenerate, which they found to be true. What’s more, they discovered that OSNs are highly susceptible to insulin deprivation-induced cell death eight to 13 days after an injury. This time window indicates that during a critical stage newly generated OSNs are dependent on insulin. They also found that insulin must be applied to regenerating OSNs at this critical time point in the neurons’ growth to be able to restore a mouse’s sense of smell.

4. Insulin promotes regeneration of regenerating OSNs in both type 1 diabetic and nondiabetic mice.

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/

Post Script:

A coming wave of diabetes? The link with COVID-19

July 2021, phys.org

An increase in new-onset hyperglycemia and abnormal hormone levels lasting months after Covid infection in Italy; "This study is one of the first to show that COVID-19 has a direct effect on the pancreas," says Fiorina.

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

Sebastiano Bruno Solerte et al, Sitagliptin Treatment at the Time of Hospitalization Was Associated With Reduced Mortality in Patients With Type 2 Diabetes and COVID-19: A Multicenter, Case-Control, Retrospective, Observational Study, Diabetes Care (2020). DOI: 10.2337/dc20-1521

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