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Club EvMed: Harmful or helpful? Cytokine storms examined in light of evolution - Shared screen with speaker view
Meredith Spence Beaulieu, Ph.D.
18:19
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Jay Labov
25:31
Lost audio for the last 30 sec.
James Gurney
25:32
Has Joe stopped for anyone else?
Negin Valizadegan
25:34
I don’t have the audio anymore.
Randolph Nesse
25:35
Joe’s video and audio froze
Robert Schopler
25:38
i can't hear anymore
Peter Woods
25:40
Yer has for me too
James Gurney
28:41
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.
Bernie Crespi
29:22
But isn’t a pandemic agent different in being a NEW infectious agent, so the immune system has no adaptation in its context
James Gurney
32:30
Correction * Would targeting the NSP of the virus work?
Charlie Nunn
33:48
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?
Eric Shattuck
34:30
Where the sepsis trials viral, bacterial, or a mix? Would pathogen reproduction/transmission strategy affect immunomodulatory treatments?
Julie Nettifee
37:29
Cytokine storms are documented as well in companion animals-J Infect Apr 10 2020 article discusses this in recent research
Sonia Cavigelli
37:37
Instead of dampening the cytokines, is it more possible to dampen the dangerous downstream effects - e.g. fever, immune cell toxicity, etc.?
Summer Mengelkoch
39:10
If you are adapted for high levels of inflammation, you might be better suited to endure a cytokine storm?
Lafi Aldakak
41:31
what does the sex difference in COVID-19 mortality tell us about the evolutionary reasons behind immune overshoot?
Peter Woods
42:51
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.
Peter Woods
43:21
Sorry that wasn’t finished!
Peter Woods
44:59
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?
Randolph Nesse
45:01
Yes, would love to hear more about Peter’s question. Could we predict who has too much and who has too little immune response?
Alvaro Daschner
45:44
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
Michelle Blyth
46:06
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?
Catherine Salmon
46:23
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
James Gurney
46:29
CD4 and cd8 cell counts are typically associated with COVID19 recovery.
Bi,ll Primack
50:23
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.
Alvaro Daschner
53:15
I think the immune system is adapted to "predict" to have contact with unknown pathogens
Melissa Franklin
54:04
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?
Bernie Crespi
54:06
Perhaps only in childhood; not so much in adulthood
Adam Hunt
54:08
I'm interested in Charlie's question earlier: Do we see similar overshoots of the immune system in other species?
Peter Woods
57:10
Only antibody responses, there’s evidence that there’s T cell immunity that lasts in other seasonal coronaviruses somewhere
Bernie Crespi
57:55
Bats rely very little on inflammation as an antiviral response; this observation would imply human immune maladaptation to covid-19
Alan Penman
01:00:01
Do bats and pangolins have modified innate immune responses, specifically differences in their interferon systems, that allow them to act as reservoirs?
Sofia Carrera
01:00:40
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?
Bernie Crespi
01:00:59
Bats have constitutive interferon expression, not inducible like humans
Amy Anderson
01:01:21
Does anyone know whether pregnant individuals have higher or lower morbidity with Covid infection?
Bernie Crespi
01:01:41
Covid-19 also has specific anti-interferon adaptations
Melissa Franklin
01:03:16
Dr Crespi, is anyone using interferon therapy for CoVid?
Eric Shattuck
01:03:17
Bernie, I remember seeing the idea that in bats, flight acts as an ersatz inflammatory response by elevating body temp.
Alcock Joe
01:04:09
what are bat’s body temperatures?
Randolph Nesse
01:05:21
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?
Bernie Crespi
01:05:23
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)
Bernie Crespi
01:06:19
Bat body temps go WAY up in flight and way down in torpor
Catherine Salmon
01:07:06
Randy, with regard to your question, also why are some older folks still managing to recover well. Differences in robustness?
Neha Shet
01:07:24
how is evolutionary respoce to viruses over the years fit into this conversation??
Peter Woods
01:07:55
You’re as old as you feel Randy!
Bernie Crespi
01:08:51
Need a multiple regression, survival on age, sex, and preexist conditions; I have not seen these results anywhere
Julie Nettifee
01:09:50
Thank you-great presentation!
Katherine Ward
01:09:58
Thank you this was fascinating
Alcock Joe
01:10:02
Thank you for great questions everybody!
Ben Trumble
01:10:05
Thanks s much Joe!
Eric Shattuck
01:10:09
Thanks Joe, thanks everyone!
Adam Hunt
01:10:17
Excellent, very interesting, thanks everyone
Neha Shet
01:10:19
Thank you that was amazing!!!
Sam Urlacher
01:10:20
Thanks, Joe! Great discussion.
Edward Clint
01:10:24
Thanks everyone!
Tyler DeJong
01:10:47
Thanks!
Alcock Joe
01:10:54
Terrific. I look forward to the next one
Peter Woods
01:10:54
Thank you, stay safe everyone