A previously healthy 39-year-old man developed highly symptomatic post-COVID-19 condition (also known as long COVID) marked by cognitive dysfunction, disabling fatigue, and autonomic symptoms unresponsive to multiple multidisciplinary interventions. Given the presence of markedly elevated serum autoantibodies against G protein-coupled receptors, high-dose intravenous immunoglobulin therapy was initiated at 400 mg/kg per day for 5 consecutive days. After 4 weeks, a maintenance dose of 500 mg/kg was administered for 1 day, followed by two further maintenance cycles consisting of 500 mg/kg per day for 3 consecutive days, each given at 4-week intervals. In parallel, the patient underwent a cognitive stimulation intervention. Neurological symptoms were assessed with the Fatigue Assessment Scale and the WHO Disability Assessment Schedule 2.0, and the immunological profile was longitudinally analysed during intravenous immunoglobulin treatment. Fatigue scores normalised, neurocognitive performance returned to normal value, and quality of life improved after the first infusion and fully recovered within 1 year. Immunological profiling revealed the presence of an inverted CD4 to CD8 T-cell ratio that persisted during the whole follow-up. We also identified a CD8+ T cell–monocyte complex and spontaneous IFNγ release. Intravenous immunoglobulin therapy was associated with a significant reduction of these complexes, spontaneous IFNγ and TNF production, markers of endothelial inflammation, and circulating autoantibody titres. This patient provides exploratory evidence that high-dose intravenous immunoglobulin was associated with sustained clinical recovery from long COVID over 1 year of follow-up, accompanied by immunological changes consistent with modulation of post-viral immune dysregulation, including a reduction in pathogenic T cell–monocyte synapses. Although causal inference cannot be established from a single patient, these findings suggest that this cellular interaction can contribute to long COVID and that immunomodulation could represent a rational therapeutic approach to be evaluated in selected patients.
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