Matthew’s theory, which is his, about why Covid-19 and other viral infections often reduce one’s sense of smell

Matthew tweeted his new theory, which is his, about why Covid-19 patients very often experience “smell blindness”, technically known as anosmia—the loss of one’s sense of smell (which of course also reduces one’s ability to taste). I asked him if he wanted to post it here, and he’s rewritten it so it’s understandable by the science-friendly layperson. And so, without further ado:

A hypothesis to explain why the Covid-19 virus affects the sense of smell in some people

By Matthew Cobb

 

In a recent study by King’s College, London of 579 people who reported having a positive Covid-19 test, 59% said they had reported a loss of smell or taste. This is not unique to Covid-19 – many other viruses can cause the same effect. It has never been quite clear how this occurs. The great amount of attention being paid to Covid-19 has helped reveal one possible mechanism.

We smell volatile molecules, but we don’t directly detect them in the air – our smell neurons would shrivel up and die. Our neurons are protected by a layer of mucus, and the smell molecules have to get through that.

The chemical structure of most smells means they are what is known as hydrophobic – they won’t dissolve easily in water, such as that found in the mucus. It is widely thought that the smells are transported by rather mysterious chaperones called olfactory binding proteins (OBPs).

These molecules are secreted into the mucus by cells called Bowman’s cells in the olfactory epithelium – the layer of skin, high up in the roof of your nasal cavity, which is where you smell things. Many scientists think that OBPs deliver the odour to the receptor on the neuron, and then appear to be taken up by cells called sustentacular cells which lie next door.

A paper that appeared a few days ago suggests that our olfactory neurons don’t express the ACE proteins that are the virus target, and that disruption to our neurons is therefore not the cause of anosmia. However, other cells in the olfactory epithelium, the sustentacular cells and the Bowman’s cells that produce OBPs, do express the ACE protein. Both these cell types are involved in the way that OBPs work.

If the virus is attacking these cells, then the metabolism of OBPs, and thereby the balance of detection of molecules will be altered. This may explain the widespread reports of anosmia following covid-19 infection, and, in some cases like that of the science journalist Adam Rutherford, who had symptoms of covid-19,  hyperosmia (increased sensitivity). Sustentacular cells are also electrically active in newborn mice, perhaps indicating a more complex function for these cell types.

All this suggests that the return of normal olfactory functioning in patients with covid-19, or other coronaviruses, which may also cause these effects, probably depends on the time it takes for the Bowman’s cells and the sustentacular cells to recover.

A simpler explanation – advanced by @stevenmunger on Twitter in response to this – is that infection of these specific cell types merely causes inflammation, which alters tissue function. There may be other hypotheses, too. And some scientists don’t agree that OBPs play much of a role at all in olfaction. “For example, although humans have a number of genes that encode for OBPs, only one kind has so far been identified in the human olfactory epithelium. We clearly need to understand more about this aspect of how we smell.”

Whatever the exact mechanism involved, as Prof Tim Spector of King’s College said: “When combined with other symptoms, people with loss of smell and taste appear to be three times more likely to have contracted Covid-19 according to our data, and should therefore self-isolate for seven days to reduce the spread of the disease.”

For advice on living with anosmia:

fifthsense.org.uk

abscent.org.uk

BBC report of the King’s College study:

https://www.bbc.co.uk/news/health-52111606

References:

Brann et al (2020) – Gene expression in olfactory epithelium, on covid-19 and entry:

Strotmann & Breer (2011) – OBPs and sustentacular cells

Vogalis et al (2005) – Electrical activity in sustentacular cells

Badonnel et al (2009) – OBPs secreted by Bowman’s cells

 

38 Comments

  1. GBJames
    Posted April 1, 2020 at 11:57 am | Permalink

    sub

  2. ThyroidPlanet
    Posted April 1, 2020 at 12:01 pm | Permalink

    Cool

  3. Nell Whiteside
    Posted April 1, 2020 at 12:13 pm | Permalink

    Thank you both. Fascinating!

  4. Ken Kukec
    Posted April 1, 2020 at 12:17 pm | Permalink

    My theory (which is my own) is that there may be an evolutionary advantage to the loss of the sense of smell — in that folks stuck in a quarantine situation tend (save for the incessant hand-washing) to let personal hygiene slide a bit and tend to hunt around in the back of the fridge for dicey left-overs to eat rather than risk a trip to the grocery store. 🙂

    • JezGrove
      Posted April 1, 2020 at 2:52 pm | Permalink

      Interesting findings, Ken – sample size of one? (I know you know I’m kidding, but after my “I know it’s only rioja and roll, but I like it” fail on this site yesterday I just want to be extra careful.) Now I just need to roll a double six and I get first choice of the dicey leftovers in our fridge…

  5. BobTerrace
    Posted April 1, 2020 at 12:21 pm | Permalink

    Fascinating. Thanks.

  6. ThyroidPlanet
    Posted April 1, 2020 at 12:22 pm | Permalink

    I have always noticed I can detect “a smell of having a cold”, or, I seem to notice an aroma of getting/having a cold. Perhaps it might be a “metallic” smell, FWIW. Unfortunately I never paid attention to smells of other things, like banana, or garlic, cinnamon, etc.

    BTW I read it’s ACE2, not just ACE. Obviously there could be isoforms, post translational modification or something- , didn’t look at details but just sayin’

  7. Matt
    Posted April 1, 2020 at 12:28 pm | Permalink

    It’s a hypothesis, not a theory.

  8. rickflick
    Posted April 1, 2020 at 12:45 pm | Permalink

    Good idea. I know my sense of smell seems attenuated during a cold or flu – at least with some of them I’ve had.

    • Posted April 1, 2020 at 11:30 pm | Permalink

      I have always figured that was due to the fact that I had a ton of mucous in my nose, couldn’t smell and so couldn’t taste. This brings out and interesting alternative explanation.

  9. Posted April 1, 2020 at 1:34 pm | Permalink

    I found this very interesting since I suffer from anosmia—though not as the result of the coronavirus. I suffered a concussion at age 9 or so when I fell out of a tree and landed on my head on a rock. Besides requiring 16 stitches, the fall deprived me of my sense of smell and most of my sense of taste.

    Unfortunately, I fall into the 10-20% category of those whose loss of smell is permanent after a concussion. I say “unfortunately,” but there are some definite advantages when it comes to, say, changing diapers or kitty litter.

    I sometimes amuse myself by imagining that some graduate student will one day do a doctoral thesis on the lack of olfactory images in Miranda’s poetry. (Clearly, the fall didn’t compromise my megalomania–unless that itself is also a side-effect.)

    • loren russell
      Posted April 1, 2020 at 2:17 pm | Permalink

      About 25 years ago in a softball game, I suffered facial injuries from a “bad-hop” ground ball. After repair, I lost ability to recognize certain smells — but not ALL. For instance, I then taught a mushroom foraginf class, and often demonstrated that certain Agaricus that had a phenolic odor were mildly poisonous, while very similar, but very edible species had a subtle “almond oil” odor. It had always frustrated me that a fraction of my students couldn’t detect these odors.

      So, the autumn following my injury, I, too, lacked the ability to recognize either of these odors.

      A bit of this has come back over the years: I can generally detect both phenolics and almond scents from my medicine chest or spice cabinet. But not at all reliably when I check the mushrooms. So now I don’t bother collecting some likely lovely Agaricus.

    • Ken Kukec
      Posted April 1, 2020 at 2:52 pm | Permalink

      That conk on the noggin have somethin’ to do with your views on politics and spirituality, Gary? 🙂

      At least the fall didn’t seem to hurt your sense of taste in literature none.

      • GBJames
        Posted April 1, 2020 at 2:56 pm | Permalink

        LOL. I saw that opportunity but refused to enter the room!

        • Ken Kukec
          Posted April 1, 2020 at 4:19 pm | Permalink

          What’s that they say about fools rushing in?

      • Posted April 1, 2020 at 7:49 pm | Permalink

        “That conk on the noggin have somethin’ to do with your views on politics and spirituality, Gary?”

        Now that you mention it, Ken, I fell from the tree just a few hours after watching “Flying Tigers” at the Neptune Theater in Seattle. So a part of my brain may have permanently locked into emulating John Wayne. Thanks for the reminder. . .pilgrim. 😊

    • rickflick
      Posted April 1, 2020 at 3:23 pm | Permalink

      A friend, back in the late 60s was banged pretty hard on the top of the head in a car accident. For the first month or so of recovery, his memory was only very temporary. After 2 minutes he couldn’t remember what had been said by anyone present. After a while he got over that – caused by brain swelling. But, he did not regain his sense of smell which was almost a complete loss.

      • Ken Kukec
        Posted April 1, 2020 at 6:03 pm | Permalink

        For the first month or so of recovery, his memory was only very temporary. After 2 minutes he couldn’t remember what had been said by anyone present.

        That condition — anterograde amnesia — albeit in permanent form, was the story conceit of Christopher Nolan’s movie Memento, a film that’s told essentially in reverse chronological order.

        • ThyroidPlanet
          Posted April 1, 2020 at 6:31 pm | Permalink

          I recall a TED talk by Daniel Gilbert in which he discusses… I want to say RETROgrade amnesia.

        • rickflick
          Posted April 1, 2020 at 6:42 pm | Permalink

          It was a remarkable condition. We visited him in the hospital a few days after the accident where he sat up in bed surrounded by 7 or 8 visitors. He’d ask his dad what time it was, and then two minutes later ask again as if he’d never asked. The conversations were strange and rather circular. About a week later he was home and practicing his sax. Conversation was slow, but pretty much normal. After a few months, he showed no ill effects, other than the loss of smell.

        • rickflick
          Posted April 1, 2020 at 6:42 pm | Permalink

          I’ll check out the Nolan film. Thanks for the tip.

  10. Mike
    Posted April 1, 2020 at 2:02 pm | Permalink

    I rewatched “Contagion” a few nights ago. Any movie that kills off the Gwyneth Paltrow character in the first 15 minutes is ok by me.

    A fun detail of the virus in that story was a mutation that allowed it to attack both lung cells and neurons (and cause brain damage). The movie doesn’t explain how that could happen. I realized after reading Matthew’s post that this is the plausible route via sensory neurons in the nose. If viral infection stimulated those neurons to express ACE then voila.

    • Posted April 1, 2020 at 2:11 pm | Permalink

      I noticed a lot of “Contagion” type movies on Netflix and other movies now on the Internet, Cable and other places.

    • rickflick
      Posted April 1, 2020 at 3:33 pm | Permalink

      Who remembers The Andromeda Strain, about a team of scientists racing against time to destroy a deadly alien virus that threatens to wipe out life on Earth. Based on a Michael Crichton novel.

      • ThyroidPlanet
        Posted April 1, 2020 at 3:48 pm | Permalink

        Great read – one of my one-day reads.
        Awesome movie

        However

        I discovered it late – so I viewed the movie through a lens of retro/B-movie style – but the story was riveting.

        They don’t make – meaning, write – them like that anymore.

        • ThyroidPlanet
          Posted April 1, 2020 at 5:17 pm | Permalink

          What I mean here is that I saw it way way after it was released. So at the time, it probably came across as high tech, but so many years later, as movie making tech got way more sophisticated, it came across as… in a word… cheesy.

      • Mark R.
        Posted April 1, 2020 at 4:59 pm | Permalink

        Isn’t that the one where the town drunk didn’t get sick because of alcohol/ethanol in his system? I remember liking that movie too (assuming that’s the movie).

        • ThyroidPlanet
          Posted April 1, 2020 at 5:07 pm | Permalink

          “SQUEEZE!”

          But specifically, it was pH … I think

          The baby cried a lot, exhaling lots of CO2
          The drunk … hmmm… sounds like I just found the next book I’ll read … if only there was a library open…

        • ThyroidPlanet
          Posted April 1, 2020 at 5:13 pm | Permalink

          “The scientists learn that the current form of Andromeda grows only within a narrow pH range; in a too-acidic or too-alkaline growth medium, it will not multiply. Andromeda’s ideal pH range is 7.39–7.43, within the range found in normal human blood. Jackson and Ritter survived because both had abnormal blood pH (Jackson acidotic from consumption of Sterno and aspirin, Ritter alkalotic from hyperventilation).”

          Source:
          https://en.m.wikipedia.org/wiki/The_Andromeda_Strain

          • Mark R.
            Posted April 2, 2020 at 11:51 am | Permalink

            Aha, that rings a bell. Thanks.

            • ThyroidPlanet
              Posted April 2, 2020 at 12:07 pm | Permalink

              Cool

              Oh by the way

              Spoiler alert.

              Sorry.

  11. Posted April 1, 2020 at 2:08 pm | Permalink

    Thank you. Unfortunately I worked in a factory for over 25 years and we sprayed graphite and there were other chemicals we were exposed to. My lack of smell diminished years ago. Drug addicts that huffed glue, paint, spray cans and did lines of cocaine also did not help their sense of smell. I wonder if loss sense of smell can be reversed over time? Can loss of smell make one more susceptible to the virus? If one cannot smell the virus may be overlooked and take hold because this symptom cannot be detected. Just a theory. Very informative thank you again.

  12. Mark R.
    Posted April 1, 2020 at 5:03 pm | Permalink

    When pot became legal here in Washington, I started vaping…it seemed less harsh on the lungs and I didn’t need very much to feel high. But after a few months, I lost my sense of smell and taste. I was pretty freaked out and stopped vaping; after a few days my smell/taste came back. Phew, that was a relief. I have no idea why that happened.

    • Torbjörn Larsson
      Posted April 1, 2020 at 7:47 pm | Permalink

      “Smoking is the leading cause of death and disease in the United States and according to the FDA, teen electronic cigarette use has skyrocketed by nearly 80 percent in the past year. Nearly half a million Americans are dying from its effects each year. Yet it’s also preventable.

      For those wishing to argue that “vaping” is safer than smoking and an effective way to quit, the Center for Disease Control (CDC), the surgeon general’s office, public health groups, and others point to the evidence disputing such a claim.”

      [ https://www.lung.org/blog/vaping-smoke-and-mirrors ]

  13. Torbjörn Larsson
    Posted April 1, 2020 at 7:42 pm | Permalink

    Finally, a tasteful COVID-19 story. Thanks!

  14. measententia
    Posted April 3, 2020 at 3:17 am | Permalink

    sub

  15. Tryo
    Posted April 3, 2020 at 8:54 am | Permalink

    Please…it is not a theory it is a hypothesis.


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