Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment, 2024, Campbell et a

I believe this should be in reference to

The figures are



Description: a, b) Peripheral blood mononuclear cells (PBMCs) from Long COVID participants show greater adherence to the human brain endothelial cell line, hCMEC/d3, in the presence or absence of 10 ng/ml TNFa (n = 5 Control, n = 7 Long COVID). Error bars are mean ± s.d. Data in a was analysed by two-way ANOVA with Tukey correction. Each datapoint represents one patient. c) PBMCs from long COVID patients in the presence of IgG, VCAM-1 or ICAM-1 blocking antibodies (n = 6 long COVID patients). Data was analysed by repeated measures one-way ANOVA with Tukey correction for multiple comparisons. Each datapoint represents one patient. d) Schematic of experiments to assess the effect of long COVID patient serum or spike protein on human brain endothelial cells. e) Exposure of hCMEC/d3 cells to 10 % serum from healthy or long COVID participants and quantification of gene expression changes by q-RT-PCR. Long COVID serum significantly increased TNF (P = 0.0006) and VCAM1 (P < 0.0001) vs control serum. f) Exposure of hCMEC/d3 cells to vehicle or 4, 40 or 400 nM S1 spike protein and quantification of gene expression changes by q-RT-PCR. 400 nM S1 spike protein significantly increased TNF (P = 0.024), TGFB1 (P = 0.0274), VCAM1 (P < 0.0001), MCP1 (P = 0.0269) and SNAI1 (P = 0.0389) vs vehicle. For e, n = 4 healthy serum samples and n = 8 long COVID serum samples were used. Scale bar – 50 µm. Schematics in a and d created with BioRender.com.

The source data can be found here:Source Data Extended Data Fig. 8

 

Since these are all samples from early in the pandemic I was wandering how "new" these findings were. It indeed turns out they submitted the paper in November 2022. I'd be suprised if they wouldn't have continued with this work and have already obtained some more results, positive or null (the largest problem with the paper are really the miniscule sample sizes). If that was the case I hope they'll publish a preprint this time around.

 

I haven't found anything on ongoing work or grants, but they mention that they are looking at biomarkers and therapeutics and other post-viral illnesses in many of the press reports (as always take these with a massive pile of salt)

"While the study focuses on long Covid patients, Campbell said the results might have relevance to people with brain fog relating to other conditions – such as ME – although extensive work would be needed to confirm that."

"Without doubt, similar mechanisms are at play across many disparate types of viral infection and we are now tantalisingly close to understanding how and why they cause neurological dysfunction in patients.”

"The concept that many other viral infections that lead to post-viral syndromes might drive blood vessel leakage in the brain is potentially game changing and is under active investigation by the team.”

www.theguardian.com/society/2024/feb/22/long-covid-brain-fog-may-be-due-to-leaky-blood-brain-barrier-study
https://www.tcd.ie/news_events/arti...ng-cause-of-brain-fog-linked-with-long-covid/

 

Wow 15 months for the paper to be published seems crazy.

 

"MRI scans in patients with #LongCOVID with or without “brain fog”. Increased “leakiness” of the blood vessels is seen (here in the temporal lobe region of the brain) in those patients with brain fog (indicated by red signal)."

 

Prof Campbell who was involved in the TCD #longCovid brain fog study mentioned chronic fatigue syndromes in passing in this radio interview. See transcript of extract in image
https://www.rte.ie/radio/radio1/clips/22359543/

 

ME Research UK

Cognitive difficulties (sometimes referred to as “brain fog”) are a key symptom of ME/CFS - and one of four required for “suspecting ME/CFS” in the 2021 NICE guidelines alongside fatigue, post exertional malaise and unrefreshing sleep. Brain fog is also experienced by many people with long COVID.

The overlap in symptom between ME/CFS and long COVID means that an article (https://go.nature.com/48PRbPM) published in February this year which aimed to investigate whether the blood brain barrier (BBB) – a membrane which carefully regulates movement of molecules between the blood and the brain, may be associated with brain fog in people with long COVID is important to consider.

Read more here: https://tinyurl.com/r34fahvh

 

Article in Nature News: COVID’s toll on the brain: new clues emerge
A leaky blood–brain barrier and inflammation might account for some of the cognitive symptoms of COVID-19.

 

It's only an animal model, but could potentially be of relevance:
SARS-CoV-2 induces blood-brain barrier and choroid plexus barrier impairments and vascular inflammation in mice.