Microneurography Reveals Unmyelinated Small Nerve Fiber Dysfunction in Long COVID

Area of Science:

• Neurology
• Electrophysiology
• Infectious Diseases

Background:

• Long COVID (post-acute sequelae of SARS-CoV-2 infection) presents with diverse multisystemic symptoms.
• Neuropathic symptoms, including pain and orthostatic intolerance, are common in long COVID.
• Small nerve fiber dysfunction is increasingly implicated in the pathophysiology of long COVID.

Purpose of the Study:

• To investigate microneurography findings in patients with long COVID.
• To identify electrophysiological abnormalities in peripheral C nociceptors and sympathetic nerve fibers.
• To correlate these findings with the multisystemic manifestations of long COVID.

Main Methods:

• Microneurography was performed on 36 long COVID patients.
• Evaluated C nociceptor function (spontaneous activity, sensitization, conduction abnormalities).
• Assessed sympathetic nerve fiber function using recovery cycle of excitability, comparing results to a normative database.

Main Results:

• 88.9% of patients exhibited objective C fiber abnormalities, including spontaneous nociceptor activity and peripheral sensitization.
• A shift in C nociceptor populations towards mechano-insensitive types was observed.
• Abnormal sympathetic nerve fiber recovery cycles indicated impaired neuronal homeostasis.

Conclusions:

• Microneurography provides novel electrophysiological evidence of small nerve fiber dysfunction in long COVID.
• These findings support the hypothesis that peripheral nerve dysfunction contributes to multisystem symptoms in long COVID.
• The results align with histological evidence of small nerve fiber loss in affected individuals.