‼️‼️📄A new paper by Akiko Iwasaki and colleagues has just been published, and it goes exactly in the direction of what I commented on yesterday. Yesterday I posted that, in a relevant subgroup of Long COVID and ME/CFS, post-exertional autonomic dysfunction could fit very well with autoimmunity against GPCRs, especially muscarinic receptors. This new work takes an important step forward because it no longer stops at “there are autoantibodies”: it shows broad autoimmune reactivity against neural and vascular/peripheral tissues, includes profiling against GPCRs and ionotropic receptors, and also demonstrates that passive transfer of IgG from Long COVID patients into mice induces pain, fatigue-like behavior, loss of balance/coordination, small fiber nerve damage, and pain-related neuronal activation, recapitulating key symptoms of the donors. That strongly reinforces the idea that, in a subgroup of Long COVID, there is indeed functionally pathogenic autoimmunity, not just a nonspecific association. Another important point is that the paper does not reduce everything to a single autoantigen. On the contrary, it shows heterogeneity, with reactivity against the locus coeruleus, thalamus, sciatic nerve, meninges, and also against peripheral tissues such as the adrenal gland and thyroid. In other words, the message is not “there is only one antibody,” but rather that Long COVID probably contains several autoimmune subgroups, some more neurological, others more vascular, others more autonomic or glandular. For me, this paper strengthens an important transition: we move from suspecting autoimmunity to having much stronger evidence of pathogenic autoantibodies in a subgroup of Long COVID. The next step should be to demonstrate which ancestral HLA-II haplotypes / susceptible alleles are behind the development of that autoimmunity. Because if we are already starting to see more clearly that there are functional autoantibodies, and that some of them can target neural, vascular, and autonomic circuits, then the logical next question is: which patients are the ones who most easily lose tolerance after SARS-CoV-2 infection?