Choroid plexus alterations in long COVID and their associations with IL-6, 2026, Cao et al

[forestglip]

Choroid plexus alterations in long COVID and their associations with IL-6

Spoiler: Authors

Cao, Yuan; Lizano, Paulo; Garza, Alejandra P.; Dunay, Ildiko Rita; Zhou, Xiaoqin; Reuken, Philipp A.; Stallmach, Andreas; Walter, Martin; Li, Meng; Besteher, Bianca

[Line breaks added]

Abstract
SARS-CoV-2 disrupts the choroid plexus (ChP) epithelium by binding to the ACE-2 receptor, causing blood cerebrospinal fluid barrier leakage and permitting interleukin (IL)-6 and pathogens into the brain, subsequently leading to demyelination, white matter (WM) damage in long COVID, and clinical worsening. The role of the ChP in long COVID and its relationships to WM integrity, IL-6, clinical symptoms, and ACEIs/ARBs medications remains unclear.

Fifty-two long COVID individuals, 21 COVID-19 survivors, and 26 healthy controls (HCs) completed Montgomery-Asberg Depression Rating Scale (MADRS), Montreal Cognitive Assessment (MoCA) and interleukin (IL) -6 assessments. Manually segmented ChP volume and global free water corrected WM integrity was compared among groups, and consideration of ACE inhibition on the ChP was examined.

Partial correlations explored relationships among ChP volume, IL-6, fractional anisotropy tissue (FAt), and symptoms. ChP changes were also assessed at baseline and after one year.

Long COVID individuals showed higher MADRS (p < 0.001), lower MOCA score (p < 0.001), and smaller ChP volume (p = 0.02) among groups. Larger ChP volume was significantly correlated to higher IL-6 levels (r = 0.478, p = 0.005) in long COVID. No ChP volume differences were found over time in the long COVID group or HCs that transitioned to COVID-19 survivors. COVID-19 survivors had larger ChP volume at follow-up compared to baseline (p = 0.04).

The smaller ChP in long COVID seems to involve persistent but low-grade blood-CSF barrier dysfunction and epithelial stress. IL-6 levels may affect ChP permeability and suggest ongoing neuroinflammation in the long COVID group.

Web | DOI | PDF | European Archives of Psychiatry and Clinical Neuroscience | Paywall

 

[forestglip]

Long COVID individuals showed higher MADRS (p < 0.001), lower MOCA score (p < 0.001), and smaller ChP volume (p = 0.02) among groups.

I don't know if these are looking at exactly the same thing, but this other study seems to be the opposite:

Choroid plexus volume is enlarged in long COVID and associated with cognitive and brain changes, 2025, Diez-Cirarda et al

One-hundred and twenty-nine patients with PCC after a mean of 14.79 ± 7.17 months of evolution since the infection and 36 healthy controls were recruited. Participants underwent a neuropsychological, and neuroimaging assessment and immunological markers evaluation. Results revealed ChP volume enlargement in PCC compared to healthy controls.

Maybe someone with access could see if they cited the older paper and commented on it.

 

[SNT Gatchaman]

Maybe someone with access could see if they cited the older paper and commented on it.

They did I think. One sec I'll dig it up.

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Actually they didn't reference that paper, instead discussing against a subacute Covid study Inflammation-Triggered Enlargement of Choroid Plexus in Subacute COVID-19 Patients with Neurological Symptoms (2024)

Those same authors had also done an LC study (ie months rather than a few weeks later) which we have a thread on: Choroid plexus volume is enlarged in long COVID and associated with cognitive and brain changes (2025). There are other increased choroid plexus studies available too.

In this thread's paper they suggest —

One study observed enlarged ChP volume was associated with higher leukocyte in subacute COVID-19 patients with neurological symptoms, indicating a relationship between systemic inflammation and barrier dysfunction, however, this study found no significant correlation between IL-6 levels and ChP volume.

In contrast, our study observed smaller ChP volume in long COVID group, while enlarged ChP was associated higher levels of IL-6 in long COVID. Despite the seemingly contradictory findings, we hypothesized that they may involve different mechanisms. […] Due to the ChP epithelium forms the barrier, these findings suggested chronic epithelial and endothelial dysregulation rather than acute inflammatory enlargement. Chronic low-grade dysfunction of this type is known to promote epithelial stress and atrophy, consistent with our observation of reduced ChP volume in long COVID and COVID-2019 survivors compared to HCs.

Additionally, beyond inflammation, ChP volume is modulated by multiple metabolic and autonomic factors. Prior studies have shown that body mass index and triglyceride levels are associated with ChP enlargement, and similar associations have been reported for blood pressure regulation. Moreover, endocrine regulators such as aldosterone and vasopressin influence ChP water homeostasis and sodium transport, both of which can affect ChP volume. These pathways are tightly linked to autonomic nervous system activity, which itself plays an important role in inflammatory control and cerebrovascular regulation.

Importantly, long COVID frequently presents with autonomic dysfunction including orthostatic intolerance, heart rate abnormalities, and impaired sympathetic/parasympathetic balance, which may further contribute to altered ChP structure. The association between elevated IL-6 levels and enlarged ChP volume may indicate that the interaction between peripheral inflammation and neuroinflammation is mediated through the well-preserved ChP, as commonly observed in psychiatric disorders.