Club EvMed: Harmful or helpful? Cytokine storms examined in light of evolution - Shared screen with speaker view
Meredith Spence Beaulieu, Ph.D.
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Yer has for me too
Would targeting the NSP of the virus, those proteins that are correlated to shift TNFa etc? To me the immune system seems overly complex target while the 3 or 4 proteins in the virus are clear targets.
But isn’t a pandemic agent different in being a NEW infectious agent, so the immune system has no adaptation in its context
Correction * Would targeting the NSP of the virus work?
What is known about this phenomenon comparatively? Do we see “dysregulation” (overshoot) in other animals, in natural settings? Or zoos? Are humans exceptional in this context?
Where the sepsis trials viral, bacterial, or a mix? Would pathogen reproduction/transmission strategy affect immunomodulatory treatments?
Cytokine storms are documented as well in companion animals-J Infect Apr 10 2020 article discusses this in recent research
Instead of dampening the cytokines, is it more possible to dampen the dangerous downstream effects - e.g. fever, immune cell toxicity, etc.?
If you are adapted for high levels of inflammation, you might be better suited to endure a cytokine storm?
what does the sex difference in COVID-19 mortality tell us about the evolutionary reasons behind immune overshoot?
Do you think it’s necessary to create sub-phenotypes in conditions such as sepsis ARDS and covid. There’s evidence that if you prognosticate individuals in you can see benefit in those individuals who have a worse prognosis. In my (limited) clinical experience of COVID there seems to be two phenotypes too.
Sorry that wasn’t finished!
Is it this more severe group where we are seeing overshoot, and is this the group where we might expect to see benefit to immunemodulation. Is this small subgroup being masked by the larger group who are having an appropriate immune response?
Yes, would love to hear more about Peter’s question. Could we predict who has too much and who has too little immune response?
Within mismatch hypothesis, risk factors for severe COVID such as obesity and diabetes, are associated with a systemic low grade inflammation. Thus immune overreaction would be predictable and this could be the cause of higher death rates in industriaized countries
As an ID fellow, I've noticed that most severe covid pts are not young and healthy, and often have comorbities that are considered immunosuppressive. I would expect if the patients that would overshoot who have very functional immune systems, but this isn't what we see. Can Joe speak to this?
Yes, because that prediction of too much or too little really could be useful in terms of knowing who is more at risk of complications
CD4 and cd8 cell counts are typically associated with COVID19 recovery.
As MERS, SARS, COVID are all pathogens that. as far as we know humans had not previously experienced, do you think from an evolutionary perspective the immune system has not learned how to react to these pathogens.
I think the immune system is adapted to "predict" to have contact with unknown pathogens
Couldn’t we hypothesize that both the energetic availability of a CoVid patient (metabolically speaking, ATP production, oxygen delivery overall, and glucose entry into cells in particular) and the faster an individual’s antibody-matching system is able to find antibodies ahead of viral replication will be key predictors of recovery from CoVid19? I am interested in hearing a response to the earlier chat question, what insights do gender differences in innate/specific immunity tell us?
Perhaps only in childhood; not so much in adulthood
I'm interested in Charlie's question earlier: Do we see similar overshoots of the immune system in other species?
Only antibody responses, there’s evidence that there’s T cell immunity that lasts in other seasonal coronaviruses somewhere
Bats rely very little on inflammation as an antiviral response; this observation would imply human immune maladaptation to covid-19
Do bats and pangolins have modified innate immune responses, specifically differences in their interferon systems, that allow them to act as reservoirs?
A recent paper found that the chronic inflammatory state in myalgic encephalomyelitis (ME/CFS) may have antiviral benefits by protecting cells from DNA and RNA viruses. What do you think about this (potential) benefit from an evolutionary perspective?
Bats have constitutive interferon expression, not inducible like humans
Does anyone know whether pregnant individuals have higher or lower morbidity with Covid infection?
Covid-19 also has specific anti-interferon adaptations
Dr Crespi, is anyone using interferon therapy for CoVid?
Bernie, I remember seeing the idea that in bats, flight acts as an ersatz inflammatory response by elevating body temp.
what are bat’s body temperatures?
Joe, do you think increased mortality in old people is completely explained by general decreased robustness or are the rates so high we should look for something else? What are possibilities?
Yes though birds also elevate; bats also reduce temperature of course; in any case the virus should be adapted to resist the temperature effects of fever (though fever also ramps up immunity)
Bat body temps go WAY up in flight and way down in torpor
Randy, with regard to your question, also why are some older folks still managing to recover well. Differences in robustness?
how is evolutionary respoce to viruses over the years fit into this conversation??
You’re as old as you feel Randy!
Need a multiple regression, survival on age, sex, and preexist conditions; I have not seen these results anywhere
Thank you-great presentation!
Thank you this was fascinating
Thank you for great questions everybody!
Thanks s much Joe!
Thanks Joe, thanks everyone!
Excellent, very interesting, thanks everyone
Thank you that was amazing!!!
Thanks, Joe! Great discussion.
Terrific. I look forward to the next one
Thank you, stay safe everyone