Thread by @x2IndSpeculator

The endemicity being forced on us is founded on a belief that the severity of #SARSCoV2 is due to novelty: once our immune system gets familiar with the virus, it will become benign, just like the other four "common cold" human coronaviruses (hCoVs).
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https://twitter.com/x2IndSpeculator/status/1420190144259313676

The linear progression of #COVID severity with age is explained by kids being freshly exposed to endemic hCoVs. That's, supposedly, why kids have mild #COVID outcomes, just like how hCoVs are now harmless for adults: they just aren't novel anymore.
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https://twitter.com/wanderer_jasnah/status/1419742332761559046?s=20

This thinking denies any special CONSTELLATION of properties of #SARSCoV2 (variants, ACE2 binding, wide viral tropism, syncytia, anosmia, brain infiltration...). Once we all get exposed to it several times by natural infection and/or vaccination, the pandemic will stop.
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But, I always feared progression in severity was reinforced by depletion & aging of some immune reservoir in the nasal mucosa. As humans age & lose that reservoir they become vulnerable to #SARS2 spreading all over their bodies no matter how many times prior exposed.
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This study's tried to find those answers.
"As the nasal mucosa is the 1st site of contact & defense for respiratory pathogens... we hypothesized that differences in this tissue across the age range may help explain the disparity in COVID-19 severity...
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medrxiv.org/content/10.110…

"We find immune cell residency in nasal mucosa DECREASES DRAMATICALLY with age especially cells of the innate immune system...
The increased presence & activity of resident immune cells in the NM of children & adolescents may be capable of clearing SARS-CoV-2 infection."
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The difference in response between children & adults holds a key to understanding #SARSCoV2's infection & #COVID's severity, thus showing us how endemicity might look like. The majority expects with repeated infections adults will resemble kids, but what if it's vice versa?
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The previous study showed immune cell residency in nasal mucosa helps fight off #SARS2 infection but decreases with age.
What about T cells? This next study confirms what @fitterhappierAJ has been trying to explain for more than a year...
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https://twitter.com/fitterhappierAJ/status/1420788137807200263?s=20

...starting with his paper in Frontiers:
"These facets depict SARS-Cov-2 as a lympho-manipulative pathogen; it distorts T cell function, numbers, and death, and creates a dysfunctional immune response."
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frontiersin.org/articles/10.33…

Now, Nature:
"SARS-CoV-2 specific T cell responses are lower in children & increase with age & time after infection."
"Therefore, REDUCED prior β-coronavirus immunity & REDUCED T cell activation in children might drive milder COVID-19 pathogenesis."
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nature.com/articles/s4146…

So, T cells might vs. #SARS2 react opposite of expected.
Is it really possible that younger less developed T cells' dampened response correlates with the milder disease, while more robust adult T cells' response might drive severe pathology, exerting autoimmunity in #COVID?
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There is no cross-reactive protection from endemic hCoVs:
"Pre-existing cross-reactive antibodies elicited by exposure to endemic human common cold coronaviruses... do not prevent infection with SARS-CoV-2."
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nature.com/articles/s4146…

But, could, contrary to common belief, previous exposures to hCoVs even make things worse?
"β-coronavirus HKU-1 & OC43-specific IgG was significantly lower in infected children than infected adults."
"There was a significant trend for both increased...
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nature.com/articles/s4146…

#SARSCoV2 specific T cell responses & OC43-specific IgG with increasing age."
"...due to differences in prior immunity to seasonal hCoVs through infection, resulting in qualitative differences in antigen-experienced CD4+ T cell responses in children."
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nature.com/articles/s4146…

I think this January 2021 article sums it up pretty good:
"Children... a higher proportion of naïve T cells in circulation than adults and, consequently, a presumed reduced susceptibility to hyperinflammatory collateral damage."
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cell.com/trends/immunol…

"While T cells play a role in the recovery of rhesus macaques from acute SARS-CoV-2 infections, their depletion does not induce severe disease, and T cells do not account for the natural resistance of rhesus macaques to severe COVID-19."
journals.asm.org/doi/10.1128/mB…

"...whether the loss of T cells contributes to severe COVID-19 or is a consequence of it... depletion of T cells slightly prolonged their clearance of virus... point toward B cell responses & antibodies as the essential mediators of protection from re-exposure."

"Coronaviruses, including SARS-CoV, MERS-CoV, and SARS-CoV-2 cause respiratory diseases with remarkably heterogeneous progression. This in part reflects the viral ability to influence the cytokine secretion and thereby the innate immune system."

https://twitter.com/NewsMedical/status/1423117799518507009?s=19

"Dysfunction of NK cells recruitment increase disease severity by leading to a higher viral load peak, the possibility for excessive macrophage activation & elevated risk of the cytokine storm... Delayed IFN-I signaling could lead to pathogenicity in latter stage of infection."

"Reversely, in case of strong NK recruitment from infected cells we predict a possible chronic disease state with moderate and potentially oscillating virus/cytokine levels."