Pediatric Long COVID Is Characterized by Myeloid CCR6 Suppression and Immune Dysregulation

[OrganicChilli]

Abstract

The biological mechanisms underlying long COVID in the pediatric population are poorly understood. Our study aimed to characterize the immune pathophysiology of long COVID in children and young people (CYP). We analyzed major immune cell compartments in PBMCs, as well as specific SARS-CoV-2 antibody response in CYP with (n=99) and without (n=18) long COVID at three months following acute infection. Our findings indicate that pediatric long COVID is associated with a dysregulated immune response characterized by altered innate immunity and overactivated T-, B- and NK-cell responses. Furthermore, CYP with long COVID had an impaired humoral response to SARS-CoV-2 marked by a dysregulated B-cell compartment and lower levels of anti-RBD IgG and IgA. This correlated with reduced neutralizing capacity against SARS-CoV-2. Random forest analysis identified CCR6 expression on myeloid cells as the most relevant biomarker that distinguishes long COVID from control individuals with 79% accuracy.

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[Utsikt]

Mild infections. The controls were on average ~40 weeks out from their last infection. For cases it was ~20.

The graphs look unimpressive at a first glance, but I’m not sure what I’m looking at so others might get more out of them?

 

[Chandelier]

Tweet/Xcretion by Zdenek Vrozina about this paper:

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@ZdenekVrozina: A new preprint study shatters the idea that pediatric long COVID is just a mild or different version of the adult form. It shows that children share the same core immune patterns - and, strikingly,...…

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A new preprint study shatters the idea that pediatric long COVID is just a mild or different version of the adult form.
It shows that children share the same core immune patterns - and, strikingly, some resemble those seen in chronic infections like HIV.
The paper message is clear - pediatric LC is biologically defined immune dysfunction.

Children display
shifts in monocytes (↑ non-classical, ↓ CCR6),
T cell changes (↑ Tregs, ↓ central memory CD4, exhausted CD8),
exhausted B cells.
At the root lies a failure of antigen-presenting cells (monocytes & dendritic cells).
Normally, they carry viral information to T and B cells. But in LC, they express less CCR6/CCR7 - they can’t migrate properly to lymph nodes or activate adaptive immunity.
“Suppressed expression of CCR6 and CCR7… could impair antigen presentation and adaptive immunity.”
The consequence?
B cells don’t mount a strong antibody response.
Children with LC had significantly lower anti-RBD IgG and IgA titers, and their antibodies neutralized the virus less effectively.
The virus can persist in tissues, like the gut.
Meanwhile, T and NK cells become hyperactivated.
On the surface this looks like a strong immune defense. But in reality, it’s a dead end.
These cells show exhaustion markers (PD1, CD57, CD38, HLA-DR↑).
“Elevated expression of activation and exhaustion markers…”
A vicious cycle?
Persistence - activation - exhaustion - persistence again.
And here’s the striking part - the authors explicitly point to parallels with HIV.
“Elevated CXCR3 expression on CD8 TCM has also been reported in people living with HIV-1, suggesting a shared trait of chronic viral infections.”
The same is true for B cells.
Cluster 15 B cells show an exhausted-like phenotype -
“…commonly observed in chronic viral infections such as HIV-1.”
SARS-CoV-2 can imprint the immune system in children in ways that mimic chronic viral disease.
In pediatric LC, CD8 stem-cell like memory T cells (TSCM) decreased, while central memory T cells (TCM) increased.
And within TCM, there was a shift toward CXCR3+/CCR6+ cells - a phenotype of chronic stimulation.
The clinical point is sobering.
Weak antibodies + exhausted T/NK cells = a recipe for viral persistence.
When APCs don’t work (CCR6/CCR7↓), B cells never make high-quality antibodies.
The virus hides, the immune system pushes harder, and burns itself out.
The result?
A state of chronic immune imbalance.
Maybe less dramatic than HIV, but uncannily similar.
Pediatric LC emerges as a model of chronic viral immunopathology - not a psychological aftermath, but a biological condition with measurable immune signatures.
And perhaps we won’t need to argue about these parallels for long.
The authors themselves are already drawing them - between pediatric LC, adults with LC, and chronic infections like HIV.