Thread by @HerbertoDhanis

There’s been a lot of talk (and evidence of course) about neurological dysfunction and neuro-inflammation in #LongCovid. So I though I would do a thread on an upcoming phase II RCT with Temelimab in LC patients with neuropsychiatric symptoms. 1/14

The trial is lead by @GeneuroO and the Hospital of Geneva @Hopitaux_unige, 1st to have an LC clinic I think + Swiss Gov granted 6.7 million CHF. To be clear I am not involved in this I just thought to share. I learned about it through @LongCovidCH some time ago. Let's start 2/14

Temelimab is a monoclonal antibody (Ig G4) developed for Multiple Sclerosis and ALS that targets the HERV-W envelope protein. It has shown success in treating progressive MS and it has anti-neurodegenerative action 3/14

journals.sagepub.com/doi/10.1177/13…

In short, HERV-W-env is a protein expressed by Human Endogenous Retroviruses type-W, known to induce degeneration of microglial cells, driving them to proximity of myelinated axons. This then structurally damages the axons 4/14

Short recommended reading:
pnas.org/doi/10.1073/pn…

So why do researchers and GeNeuro think it’s relevant for LC? The evidence mainly comes from acute-covid rather than LC, and in that sense it is a very proof-of-concept trial (which I note many LC patients have been asking for). Let's review the evidence:

5/14

Balestrieri et al. have shown that HERV-W-env is highly expressed in lymphocytes of C19 patients, expression correlates with T-cell exhaustion, cytokine levels + more lymphocytes implicated higher pneumonia severity.

6/14

thelancet.com/journals/ebiom…

Charvet et al. showed mainly three things 1. Exposure to the C19 spike protein can cause expression of HERV-W-env in cells and lymphocytes (vitro) 2. HERV-W-env is increased in serum correlating with expression in CD3 lymphocytes and clinical markers 7/14

medrxiv.org/content/10.110…

3. Strong expression of HERV-W-env in autopsy tissues of people that died with Covid-19 (they also noted expression of C19 antigens as we already know). Overall I would note that some of the effects in 1 and 2 are not very strong even if significant. 8/14

The last pieces of evidence comes from two case reports (N=41; 1) that have noted a worsening in MS patients after infection with covid-19. This might be what originally made the connection for the use of temelimab in LC 9/14
1. sciencedirect.com/science/articl…
2. sciencedirect.com/science/articl…

Feel free to also check a brief opinion paper on temelimab for LC: msard-journal.com/article/S2211-…

10/14

Imo the evidence is very indirect. While I am not a specialist I talked with some that also consider this proof-of-concept. Nonetheless it is good that things are moving and these types of trials are what some LC patients asked for. I note potential links to LC research:

11/14

First, HERV-W-env, like Sars-CoV-2 is known to trigger endothelial inflammation. There might be a link here. Second, T-cell exhaustion is noted in both Long Covid and in persistent HERV-W-env expression.

12/14

These could be supporting evidence as in the up-regulation of HERV-W-env creates a cycle leading to the above; or (probably) up-regulation of HERV-W-env might be a downstream effect in LC. Again imo the most likely candidate to cause the latter would be viral persistence.

13/14

To finish, I don’t know why they focus on neuropsychiatric symptoms, but they do include fatigue under this umbrella term. For those who might be concerned, HERV-W-env is not expressed in diseases such as Parkinson’s or Alzheimers. 14/14

@ShaneyWright @ahandvanish I am tagging you since I have seen both of you experience a significant amount of neurological symptoms. Maybe this is something to keep an eye on (as I said very proof-of-concept though). Feel free to retweet

Actually I also take the chance for this: @Karl_Lauterbach the Swiss government gave 6.7 million CHF to an experimental drug (Temelimab - see above). This is great. Now, #BC007 has much more promise and evidence. Why don't you properly fund @BerlinCures and clinical trials?