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.

Abstract

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.