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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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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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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...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."
"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."
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