Reply to: “Bridging Electrophysiology and Digital Health: Microneurography Findings in Long <scp>COVID</scp> Herald a New Era of <scp>AI</scp> ‐Powered Peripheral Nerve Monitoring”

We would like to thank Yar et al for their interest in our manuscript describing widespread dysfunction of C-fibers in patients with long coronavirus disease (COVID)1 and for their thoughtful and visionary letter. Your proposal to use microneurography-derived physiological signatures as the foundation for artificial intelligence (AI)-driven digital biomarkers is both timely and inspiring, and we fully agree that leveraging these insights could substantially advance monitoring and care for patients with long COVID and other small fiber neuropathies. The conceptual shift you outline from episodic, invasive testing to continuous, passive assessment is exactly the type of innovation the field needs. However, we would like to draw attention to a key technical challenge. The electrophysiology of pain fundamentally depends on resolving activity from individual peripheral nociceptor axons. At present, microneurography remains the only method capable of accessing such single fiber intraneural signals in humans.2 No wearable or surface-level technology can yet detect or isolate the unitary action potentials that define spontaneous activity, sensitization, or shifts in nociceptor phenotype. As a result, the digital biomarkers you envision would necessarily rely on indirect correlates rather than on direct recordings of nociceptor activity. Your proposal implies an exciting but demanding next step, which is the development of new recording strategies capable of accessing intraneural information noninvasively, or at least sensing peripheral correlates that preserve enough of the single fiber dynamics to allow AI models to infer nociceptor dysfunction. Progress in ultrahigh-density sensors or nanomaterials, novel transduction modalities, and computational source-separation techniques may eventually help bridge this gap.3 These limitations do not detract from the promise of your approach. Combining microneurography's unique single fiber resolution with advances in AI offers a credible pathway to building surrogate digital markers of small fiber dysfunction. Continued exploration at this interface could ultimately make objective, scalable autonomic and nociceptor monitoring a reality beyond specialized centers. Ana Ribeiro: Writing – review and editing. Shahrzad Hadavi: Writing – review and editing. Nick Gall: Writing – review and editing. Robert D. M. Hadden: Writing – review and editing. Jordi Serra: Writing – review and editing; writing – original draft; conceptualization. The authors declare no conflicts of interest.