Autoantibodies mediate pain and sensory dysfunction in post-COVID syndrome

Pain and fatigue are common but poorly understood features of post-COVID Syndrome (PCS). To probe the mechanistic basis of these symptoms, we investigated sensory functions in patients with widespread pain attributed to PCS. Quantitative sensory testing revealed increased mechanical pain sensitivity and altered thermal sensitivities and microneurography demonstrated that patients with pain displayed abnormal spontaneous C-fibre activity. Administration of IgG from PCS patients with pain and fatigue (PCS-PF) to mice, conferred mechanical and cold hypersensitivities and reduced intra-epidermal nerve fibre density (IENFd). IgG from patients with fatigue but without pain (PCS-F) did not induce hypersensitivities but similarly reduced IENFd. In line with behavioural responses, sensory nerves from PCS-PF IgG treated mice showed increased responsiveness to mechanical and cold stimulation. PCS-PF IgG bound to isolated sensory neurons with staining intensities that correlated with the level of pain experienced by patients with PCS. These results indicate a causal role for autoantibodies in the pathogenesis of pain and sensory disturbances associated with PCS.