Postacute COVID-19 syndrome & fibromyalgia syndrome are associated with anti-satellite glial [IgG] but only [FM] IgG is pronociceptive, 2025, Berwick+

[SNT Gatchaman]

Postacute COVID-19 syndrome and fibromyalgia syndrome are associated with anti-satellite glial cell IgG serum autoantibodies but only fibromyalgia syndrome serum-IgG is pronociceptive
Berwick, Richard J.; Sahbaie, Peyman; Kenny, Grace; Guo, Tian-Zhi; Neiland, Harvey; Andersson, David A.; Clark, J. David; Mallon, Patrick; Goebel, Andreas


Postacute COVID-19 syndrome (PACS) describes the persistence of symptoms following severe acute respiratory syndrome coronavirus 2 clearance. PACS is sometimes associated with pain and fatigue resembling fibromyalgia syndrome (FMS). Severe FMS has recently been associated with pronociceptive immunoglobulin G (IgG) autoantibodies and anti-satellite glial cell (SGC) IgG autoreactivity, suggesting an autoimmune aetiology. We validated FMS-IgG passive transfer and then tested the hypothesis that PACS-patients, with high musculoskeletal pain and fatigue, harbour proalgesic and anti-SGC autoantibodies.

PACS-patients with high pain and fatigue or people recently recovered from acute COVID-19 were recruited to the All-Ireland Infectious Diseases Study. We pooled serum from 18 patients per group and purified their serum-IgG. In addition, we obtained IgG from UK patients with FMS and healthy controls to confirm assay performance. Passive transfer experiments of IgG (8 mg/d) over 3 days were conducted using male (C57BL/6J) mice (n = 6 mice per group). We measured mechanical and cold hypersensitivities and grip strength.

Injection of FMS-IgG elicited the previously described mouse phenotype in male rodents, including increased mechanical/cold hypersensitivities and reduced grip strength compared with control IgG, whereas pooled PACS-IgG was inert. Immunocytochemistry of primary-SGC-enriched cultures reproduced the increased staining of FMS-IgG over the control reported previously. Both IgG from patients with PACS and those recently recovered from COVID-19 stained strongly positive.

We confirm the pronociceptive properties of FMS-IgG and demonstrate, in contrast, that PACS symptoms from our cohort, with severe pain and fatigue, are not transmissible through passive transfer to male rodents. Postacute COVID-19 syndrome pain is often localised, and stratification according to the widespread distribution of pain should be considered for future studies; recovered COVID-19 leaves a strong trace of anti-SGC autoreactivity.

Link | PDF (PAIN) [Open Access]

 

[Kronos]

I am kind of surprised that the long covid cohort was not screened for fibromyalgia. But I guess they had no other opportunity.

 

[SNT Gatchaman]

Some quotes, out of order —

This study confirms successful IgG-passive transfer of FMS symptoms, including hyperalgesia and reduced muscular power in male mice, replicating previous findings.

Our hypothesis that PACS symptoms can be transferred through IgG was not upheld in this cohort. Superficially, this contrasts with Chen et al.’s recent pre-pub, which suggests that IgG from patients with PACS—with high neuronal or leucocyte activation proteins titres but not skeletal muscle proteins—are proalgesic upon passive transfer. [12] The absence of symptom transfer in our cohort indicates that the pooled PACS-IgG was not pathologically autoreactive (similar to Chen et al.’s negative skeletal muscle protein group) or that an unknown adjuvant, as in CRPS, is required.

[12] is Transfer of IgG from Long COVID patients induces symptomology in mice (2024, Preprint: BioRxiv)

we found that both patients with PACS (<1-year duration) and, unexpectedly, individuals recently fully recovered from COVID-19 exhibit high anti-SCG IgG antibody titres. Pain levels in high pain/fatigue intensity groups G1 and G2 exceeded those observed from the patient with FMS. Satellite glial cell staining intensity correlates with pain scores. However, as RC2 (recovered) participants, reporting no pain or fatigue, demonstrated equally strong staining, anti-SGC staining titre alone seems insufficient to explain symptoms in PACS. Instead, high staining in the recovered PACS group likely indicates a persistent immunological imprint from recent infection (2-6 months prior).

while we detected a high titre of anti-SGC IgG antibodies in the sera of a patient with PACS, cellular reactivity was not associated with a mouse pain-sensitising effect. It appears that COVID-19 infection is associated with SGC autoreactivity, irrespective of pain symptoms.

Notably, 1 UK control sample, recruited later in the pandemic and extensively vaccinated, showed low anti-SGC antibody titres despite a prior COVID-19 infection. This suggests vaccination reduces off-target antibodies in the B-Cell response, consistent with existing research on post-COVID-19 IgG autoreactivity.