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.
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.
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.
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.
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.
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.
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.
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.
Autoantibodies could trigger neurological symptoms of long COVID
Heather Wood
First paragraph
Over 10% of people with SARS-CoV-2 infection develop long COVID (also known as post-COVID-19 condition), which has a range of neurological manifestations, including cognitive impairment, fatigue, pain and increased sensitivity to heat. A new study by Keyla de Sá and colleagues, published in Cell, provides evidence for a causal link between autoantibodies and the neurological symptoms of long COVID.
Abstract
Introduction
Acute SARS-CoV-2 infection triggers the de novo production of diverse and functional autoantibodies (AABs), even after mild illness. Previous studies have shown that autoantibodies remain persistently elevated in a subset of individuals with Long COVID (LC). However, it is still unclear whether these autoantibodies drive pathogenesis of LC
Methods
Using a human protein array with over 21,000 proteins and an antibody pull-down of autoantigens followed by mass spectrometry, we identified a broad range of AAB targets among individuals with LC that correlated with their symptom profiles. In order to evaluate if those autoantibodies were pathogenic, we developed a passive transfer mouse model by injecting total IgG in mice and performing a battery of behavior analysis.
Results
We found increased AABs against proteins in the central and peripheral nervous systems, as well as peripheral tissues, in individuals with LC displaying neurocognitive and neurological symptoms. Purified immunoglobulin G (IgG) samples from these individuals reacted with tissue sections of human locus coeruleus, thalamus, adrenal gland, thyroid, and showed cross-reactivity with mouse sciatic nerve and meninges.
Autoantibody levels reactive to CNS antigens were linked to symptoms such as headaches and loss of taste and smell. Passive transfer of IgG from patients to naïve mice caused increased fatigue-like behavior and thermal hyperalgesia, aligning with patients’ reports of chronic pain. Similarly, loss of balance and coordination in the rotarod test in mice injected with IgG matched with patient-reported dizziness.
Moreover, transfer of purified IgG from patients with chronic pain caused damage to small peripheral nerve fibers and increased neuronal activity in pain-related brain regions in mice.
Conclusion
Our findings demonstrate that transferring IgG from LC patients into mice can reproduce certain neurological symptoms, suggesting that targeting AABs might offer therapeutic benefits for this subgroup of LC.
Web | DOI | PDF | The Journal of Immunology | August 2026 | Abstract Only
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