Covid 19 may hijack pain receptors, reducing pain and increasing the spread of the virus: a possible result of natural selection

The paper below, which has just been published (click on screenshot to go to page, then click the “download” button to the left to get the pdf), has a unique twist that may say something about evolution in pathogens, but the evolutionary angle hasn’t been mentioned. It’s a complex and technical paper, using rat models (i.e., tissue and analyses), to study whether the Covid-19 virus has the ability to reduce pain.

There’s also a publicity piece from the University of Arizona that explains the results in simpler language, and a two-minute video below that dumb things down a bit, but gives the gist.

From the publicity piece:

SARS-CoV-2, the virus that causes COVID-19, can relieve pain, according to a new study by University of Arizona Health Sciences researchers.

The finding may explain why nearly half of all people who get COVID-19 experience few or no symptoms, even though they are able to spread the disease, according to the study’s corresponding author Rajesh Khanna, PhD, a professor in the UArizona College of Medicine – Tucson’s Department of Pharmacology.

Rajesh Khanna, PhD. (Photo: Kris Hanning/University of Arizona Health Sciences)“It made a lot of sense to me that perhaps the reason for the unrelenting spread of COVID-19 is that in the early stages, you’re walking around all fine as if nothing is wrong because your pain has been suppressed,” said Dr. Khanna. “You have the virus, but you don’t feel bad because your pain is gone. If we can prove that this pain relief is what is causing COVID-19 to spread further, that’s of enormous value.”

The paper, “SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia,” was published today in PAIN, the journal of the International Association for the Study of Pain.

. . .The U.S. Centers for Disease Control and Prevention released updated data Sept. 10 estimating that 50% of COVID-19 transmission occurs prior to the onset of symptoms and 40% of COVID-19 infections are asymptomatic.

“This research raises the possibility that pain, as an early symptom of COVID-19, may be reduced by the SARS-CoV-2 spike protein as it silences the body’s pain signaling pathways,” said UArizona Health Sciences Senior Vice President Michael D. Dake, MD. “University of Arizona Health Sciences researchers at the Comprehensive Pain and Addiction Center are leveraging this unique finding to explore a novel class of therapeutics for pain as we continue to seek new ways to address the opioid epidemic.”

In other words, the virus’s famous spike protein nullifies the effect of another protein, VEGF—one of the several proteins that normally causes pain. And that’s all ye need to know unless you work on this system.

But here’s where the evolution comes in. Remember, pain is an adaptation whose evolution was doubtlessly prompted by its ability to tell us that there’s something wrong, like “Hey, your hand is in the fire.” People who don’t feel pain, like those with Hansen’s disease (leprosy) and some rare neurological conditions, often incur severe damage to their bodies because they’re unaware of injuries. The reason Hansen’s sufferers lose their fingers and other bits is not because the bacteria eat away at those bits; rather, it’s because the bacteria numb feelings of pain, and so you start damaging your body without being aware of it. So pain is a good thing to have, even though it feels bad.

But if a virus that normally causes pain because it injures your innards can somehow block that pain, it might spread faster. This would be true for viruses like COVID-19, which is spread by human-to-human contact, and depends on its transmission for people going about and infecting others. If you take to bed because you’re in pain, the virus won’t spread as well.

And what that means is that mutant variants of the virus that reduce pain will spread faster than forms that cause pain. This differential would create natural selection for the mutants that reduce pain, and the virus “species” would evolve painlessness as one “symptom”.

As far as I can see, nobody in either the paper or the puff pieces have mentioned this possibility. Now we don’t know if this speculation is true, or if it’s just fortuitous that the spike protein blocks pain receptors. Further, while this might be an evolved property of the virus, it could also be an inherent property of the spike protein, evolved for other reasons, that simply allowed the virus to spread quickly.

I’m merely suggesting this as one possibility in a field called “Darwinian medicine,” which analyzes symptoms of diseases from an evolutionary viewpoint. Other suggestions from this area involve things like malaria. When you have a malaria outbreak, the malaise and fever put you flat on your back. And that facilitates the spread of the malaria pathogen (a protozoan), because that protozoan is transmitted by mosquitoes. When you’re prostrate in bed and sick, you’re not as liable to slap a biting mosquito as when you’re walking around, and so those protozoans that knock you flat will more readily find a mosquito vector. (This is all speculation, of course.)

Another suggestion involves the virus for the common cold. It doesn’t debilitate you, but rather makes you a bit grotty but still able to walk around—and transmit the virus to other people. If a common cold were to knock you out like malaria, the virus wouldn’t spread so well.

And so many of the symptoms that are caused by pathogens may well have evolved in those pathogens to facilitate their own transmission. This must certainly be true in some cases, but of course proving it is very hard to do. You couldn’t do experiments in humans, though I suppose you could in model animals like rats, but I wouldn’t be keen on hurting animals to test evolutionary hypotheses. (I even anesthetized all my fruit flies before killing them.) It is curious, though, that I haven’t seen this new and striking result mentioned as a possible example of natural selection in the virus.

Here’s the video, though you might not learn much if you’ve read what’s above.

h/t: Charles

Click to access 2020.07.17.209288.full.pdf

23 Comments

  1. GBJames
    Posted October 8, 2020 at 9:04 am | Permalink

    Makes sense.

  2. ladyatheist
    Posted October 8, 2020 at 9:15 am | Permalink

    Considering that it blocks scent and taste, this seems plausible to me. It would also explain why people get sick “faster” — they are “fine” until things have gotten out of control.

    Next thing to wonder: how much coffee would one need to drink not to wonder why the word “analgesic” doesn’t refer to butt disease.

    • EdwardM
      Posted October 8, 2020 at 10:34 am | Permalink

      Welp, hate to spoil your joke but that’s because the prefix “an”, signifying negation, modifies the adjective “algesic” which means “causing or related to pain”.

      HTH

    • enl
      Posted October 8, 2020 at 3:05 pm | Permalink

      When I was young, irreverent, was still forced to THE CHURCH by a parental unit, and had a poor vocabulary, I first heard the word. I didn’t see it in writing. The speaker had a bit of a twang in his voice.

      I heard ‘anal jesus’. Made sense to me at the time.

  3. KD
    Posted October 8, 2020 at 9:31 am | Permalink

    That is really interesting. I wonder if there is a way of adapting a corona virus into some kind of pain management therapy for chronic pain conditions.

  4. Posted October 8, 2020 at 9:32 am | Permalink

    Now I understand why Trump feels better than 20 years ago.

    Perhaps viruses make you cough and sneeze to get spread.

    • Posted October 8, 2020 at 11:31 am | Permalink

      I thought the same thing about sneezing. It doesn’t seem likely to help the nasal tissues cope with a viral attack. I would guess that sneezing helps mammals keep dust and small insects from causing nasal/sinus trouble. And viruses cause similar irritations as dust and insects, because it helps them spread.

      I think Trump feels better because of steroids. This is your president on drugs (any questions?)

      • boudiccadylis
        Posted October 8, 2020 at 12:02 pm | Permalink

        Remember President Kennedy lived on steroids.

  5. ThyroidPlanet
    Posted October 8, 2020 at 9:39 am | Permalink

    “The reason Hansen’s sufferers lose their fingers and other bits is not because the bacteria eat away at those bits; rather, it’s because the bacteria numb feelings of pain, and so you start damaging your body without being aware of it. ”

    WOWWWWWWWW

    I never knew that! Insight!

  6. kraeuterbutter
    Posted October 8, 2020 at 9:44 am | Permalink

    To quote Mr. Spock: “Fascinating”

  7. Steve Gerrard
    Posted October 8, 2020 at 11:05 am | Permalink

    It seems like a virus would undergo a lot of natural selection, since it is cranking out lots of offspring in lots of hosts. There is bound to be some selection for any properties of the spike protein that increase its spread, and against any that reduce it. 50% of transmission occurring before symptoms appear is a big effect, too. It may all be fortuitous, I suppose, but it sure sounds like natural selection for an adaptive property.

  8. rickflick
    Posted October 8, 2020 at 11:34 am | Permalink

    The universe seems to spend a lot of time trying to give us grief. It’s better to know thy enemy though.

  9. gravelinspector-Aidan
    Posted October 8, 2020 at 2:27 pm | Permalink

    There is another story going around that COVID-19 can adversely affect male fertility. Some people will be upset by this, and there are speculations that this is the news that will mean a vaccine is developed next Thursday, or sooner. It is even reported in the Daily Flail, so it must be true!
    Unfortunately, as far as I could be bothered to chase it, it seems to be “science by press release – no formal publication, no technical details on the study (size, significance of results, the usual suspects), so it gets the level of credence one normally associates with stories the Flail picks up (though they haven’t linked it to a threat to house prices. Yet.) However, it’s hardly the first. For a serious disease to affect fertility is about as surprising as decapitation affecting fertility. And even my fairly cursory googling shows discussion of COVID’s potential for fertility sequels back in March this year. The medical “establishment” (from stage left, blasting like a Trumpet : “What would they know? Ask an expert with personal experience!”) have also been giving the topic consideration since at least July.
    With projected population mortality rates in the order of 0.02%/year, this isn’t an existential threat to the species, regardless of how much suffering it causes.

    Aren’t we overdue for more incoherent rage-tweeting from the Oval Orifice? It’s been at least an hour.

    • infiniteimprobabilit
      Posted October 8, 2020 at 5:33 pm | Permalink

      Considering the continuing menace that overpopulation constitutes, that’s probably a Good Thing. The world doesn’t need more babies.

      Far better way to control population than killing off people (which seems to be an unfortunate side effect of covid 😉

      cr

    • Posted October 9, 2020 at 3:21 am | Permalink

      If it becomes a widespread rumour, maybe the good ol’ boys with their guns will start wearing their damn masks.

  10. Posted October 8, 2020 at 3:05 pm | Permalink

    Cool. Thanks for the explainer Jerry!

  11. Posted October 8, 2020 at 3:06 pm | Permalink

    Very interesting evolutionary analysis

  12. Posted October 9, 2020 at 1:39 am | Permalink

    Perhaps researchers will be able to hijack aspects of the gene to create treatments for those with chronic pain…

  13. Posted October 9, 2020 at 3:22 am | Permalink

    The correlation to that is that even asymptomatic cases might result in long term damage. Is that correct?

  14. Andrea Kenner
    Posted October 14, 2020 at 7:22 am | Permalink

    Interesting!


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