Efthymios Kalafatis

1) Using a state-of-the art #AI committee (=multiple reasoning #AI engines investigating the same problem) we have two new #MECFS and #LongCOVID research targets being confirmed : a) Phosphoinositide-controlled membrane identity b) The role of RAB Proteins and prenylation.

1) 🇪🇸 A new Spanish study measured autoantibodies against adrenergic and muscarinic receptors in 59 patients with ME/CFS, 96 Long Covid and 36 healthy controls. The results show a large overlap, questioning whether these antibodies are involved in ME/CFS pathology.

YESSS!!!! Congrats Chris Ponting and team

3) Efferocytosis is still an important factor for Post Exertional Malaise (hypothesis) and complements the proposed research targets discussed in the first post. Findings of -consistently- elevated CD24 may be causing impaired efferocytosis (hypothesis)

2) Input data used : Genomics, eQTL colocalisation, gene-network analysis, metabolomics, lipidomics, proteomics, extracellular-vesicle proteomics, immune phenotyping, ion-channel functional assays, biomarker assays, exercise-challenge omics, and computational metabolic modelling.

1) Using a state-of-the art #AI committee (=multiple reasoning #AI engines investigating the same problem) we have two new #MECFS and #LongCOVID research targets being confirmed : a) Phosphoinositide-controlled membrane identity b) The role of RAB Proteins and prenylation.

I want to ask you to follow this dot with your eyes. Was that easy? Without you even having to give that much thought, your brain is telling your eye muscles where to move to keep your focus on that dot. 1/

2/ Caution : zinc supplementation inhibits copper. Make sure you do any supplementation under specialist guidance.

1/ After all of these years, I forgot about the importance of zinc. If you are an #MECFS, #LongCOVID patient and especially if you are male, do look at your zinc levels. Important for CYP11A1 (P450scc). Below, snapshot from my presentation at @LSHTM (2018)

@DuaneStorey See also here regarding NAG : x.com/i/status/18084…

I've spent the last month or so looking over all my own RNA data, and that of other covid19 patients. I've been working on an overarching theory about what I think long covid might be. I still have lots of gaps to fill, but I'm leaning towards that it's actually a failure of glycosylation involving the hexasamine pathway. It's one of the only things I can think of that explains most of the observations. My own data supports this as well. This is similar to the Itaconate Trap that's been proposed, but at a higher level, involving the very mechanism that senses energy and creates UDP-GlcNAc, which is used in almost every downstream process in the body - T cells, peptides, mitochondria, mucin, etc.. It's a single choke point that could eventually lead to the failure of the Golgi apparatus, which then becomes a self-sustaining loop. Sars-Cov-2 actually overwhelms this entire pathway during an acute infection, so I can imagine a critical point where it collapses and can't recover - the energy required to break this system is less than the energy required to fix it. Once I get the results from my current longitudinal RNA. seq data over the next 90 days, I'll try to formalize this a bit more. But almost every observation in the long covid and possibly ME/CFS space can be re-imagined as a consequence of a failed glycosylation at a system level. Disease of glycosylation do exist, and many of them produce auto-immunity, vascular issues, neurological issues, and even death. All from one or two gene issues with catastrophic downstream consequences. This is pretty out there, but I'm working hard on connecting all the pieces to at least come up with what a testable hypothesis would look like, and will do a huge blog entry when I'm ready. rarediseases.org/rare-diseases/…

@arta_semita @DuaneStorey Yes, N-Linked glycosylation most likely

@DuaneStorey @lifeanalytics

@fidjissimo Using #machinelearning to research #mecfs changed my life. I am sure #AI can do much more : healthrising.org/blog/2023/10/0…

If there is one good thing that can come out of having my health issues exposed to the world, it’s raising awareness for complex chronic conditions like POTS, MECFS, Long Covid or EDS. 🧵 businessinsider.com/what-is-pots-f…

@Gmwetz @AnneliseBocquet @SitSilver @ZdenekVrozina Thank you @Gmwetz ! @AnneliseBocquet I believe we have been finding potential issues in certain efferocytosis-related topics for #MECFS as well. Please check the following thread and see related studies. FYI @ImmunoFever : x.com/lifeanalytics/…

@AnneliseBocquet @SitSilver @ZdenekVrozina FYI @lifeanalytics Efferocytosis

An interesting new review proposes that Long COVID is not just about what keeps the immune system on, but also about what fails to turn it off🧵

1/ I want to explain a bit about our MIT MAESTRO study. 🧵How can we help you get better if we don't know what's making you sick? If we don't currently have a way to identify what's going wrong, and we don't have the right tests, I think we need to MEASURE ABSOLUTELY EVERYTHING.

3/ Please note, I am in no position to be certain or make any claims that SPMs are responsible for this change but I felt I had to report this.

2/ .. (lately I was finding it hard to sit in my car for more than 10 minutes) went away literally in 4 days of SPM supplementation. Initially, I changed my mattress to a harder one and saw roughly a 10% improvement. It appears that SPMs were a game changer.

1/ What I experienced with the use of SPMs (Pro resolving mediators) is simply amazing. The idea was to use SPMs for improving efferocytosis. I do not have any #MECFS symptoms so I can't tell anything about improvements but a lower back pain I had for over 2 months...

@AnilvanderZee @mecfsskeptic @AnilvanderZee could you ask Marc Veldhoen if these findings could be attributed to impaired efferocytosis ? Could you also forward to him this table : docs.google.com/spreadsheets/d…

@mecfsskeptic Response Marc Veldhoen.

1) New Polybio study reports: "We confirmed the persistence of SARS-CoV-2 Spike transcript and protein in the gut tissue of all LC cases and controls tested." So while RNA and proteins from the virus were present, these were found in controls as well.

We are one person away from completing our sex and age matching for our MAESTRO study! One 56-65 year old male with long COVID who can come to MIT in person and this first chapter of MAESTRO will be complete!!!

5/ Disclaimer : This thread DOES NOT suggest in any way to supplement with Fucoidan, SPMs, or PPAR Agonists. Talk to your Doctor before any intervention ! Further research is needed as to whether these compounds are indeed beneficial to patients !

4/ It is also possible that an approach using multiple compounds is needed for better results, for example Fucoidan + Pro-resolving mediators (SPMs) and/or PPAR agonists. Moreover Fucoidan could be -according to AI below (may contain errors) - a compound to improve Fibrinolysis.

3/ It appears that Fucoidan matches with many key aspects that are important for proper efferocytosis. ABCA1, LXR, GAS6 / MerTK are regulated by Fucoidan (all these concepts were found by studies - see previous post). Some relevant studies regarding fucoidan shown below :