A causal link between autoantibodies and neurological symptoms in long COVID, 2024, Santos Guedes de Sa, Iwasaki et al

EndME said:
It looks like none of the mouse transfer experiments were blinded and they then repeated the hot plate test with blinding?

For some of the experiments it seems they only tested LC vs healthy controls, but not convalescent controls (for example the IENF experiment).

They did introduce quite a few new experiments compared to the initial preprint, for example including Scheibenbogen with her CellTrend assay.


Just that in most of the experiments and analysis there was nothing significant and as far as I can see the number of experiments and different tests was not accounted for.
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Sorry what do you mean by nothing significant? They transferred IGG and noticed symptoms and the difference can be seen vs healthy controls.

Of course there is some difficulty in trying to quantify mouse behavior, but I see a difference.
 
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ryanc97 said:
Sorry what do you mean by nothing significant?
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In most of the observations there appears to be no significant differences and it looks like number of experiments and tests was not accounted for. They possibly did hundreds of different tests if they even report an association with tinnitus and the grip strength results. To me it seems like they only had more confidence in the hot plate test.
 
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ryanc97 said:
Sorry what do you mean by nothing significant? They transferred IGG and noticed symptoms and the difference can be seen vs healthy controls.
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Life in the lab is a lot more complicated than that!
Experiments like this are notorious for not being replicable.
To the extent that I am not sure I would ever make up my mind on a theory on the basis of data like this.
 
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Jonathan Edwards said:
Life in the lab is a lot more complicated than that!
Experiments like this are notorious for not being replicable.
To the extent that I am not sure I would ever make up my mind on a theory on the basis of data like this.
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The T cell theory is more complicated than that! And I would not make up my mind on a theory on the basis of the data. But hang on. Where is the data?
 
Jonathan Edwards said:
I am not sure which T cell theory you are alluding to. But if we want data implicating t cells the BTN2A1 genetic link, replicated in the rare gene study, is the sort of data that over the years has proven far more reliable than antibody transfer experiments with mice.
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Your own T cell theory. For me the highest weight of evidence is the Dara study, simply because of the design of the trial.

In other words, all theories need to have their priors shifted to weigh for this new evidence.
 
ryanc97 said:
Your own T cell theory.
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The only theory I have actually published involves antibody as well, you might not have noticed.

ryanc97 said:
In other words, all theories need to have their priors shifted to weigh for this new evidence.
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Quite, but as a professional B cell immunologist I would say that this recent paper adds weight to a negative view of specific autoantibodies. Papers nearly always try to claim a positive result, but sometimes what stands out is that it wasn't quite as positive as it might have been. If you ask someone if they found El Dorado and they say they found four or five ruined places that looked as if they might have had a bit of gold on the stones you tend not to be too convinced.
 
Research Highlight about this study:

Pathological potential of autoantibodies in long COVID
Lucy Bird
First paragraph
Neurological symptoms are among the most debilitating features of long COVID, but their underlying mechanisms remain poorly understood. Santos Guedes de Sá et al. provide evidence that diverse autoantibodies raised during acute SARS-CoV-2 infection persist in individuals with long COVID and contribute directly to these manifestations.

Web | Nature Reviews Immunology | Paywall
 
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