Retinal, Cutaneous, and Neuromuscular Biomarkers in the Characterization of Long-COVID and Post-Infectious Dysautonomia: A Multidisciplinary Approach
DOI:
https://doi.org/10.70577/asce.v5i3.1101Keywords:
Long-COVID; dysautonomia; retinal biomarkers; small fiber neuropathy; electromyography; postural orthostatic tachycardia syndrome; multidisciplinary approach.Abstract
Long-COVID or post-COVID syndrome (PCS) affects millions worldwide, characterized by persistent symptoms including fatigue, dysautonomia, neuropathic pain, and cognitive impairment. Post-infectious dysautonomia, frequently manifesting as postural orthostatic tachycardia syndrome (POTS), constitutes one of the most debilitating complications. The identification of objective biomarkers in accessible systems such as the retina, skin, and neuromuscular system is fundamental for diagnosis and monitoring.
Objective: This systematic review aims to synthesize current evidence on retinal, cutaneous, and neuromuscular biomarkers in the characterization of Long-COVID and post-infectious dysautonomia, as well as to explore the implications for a multidisciplinary diagnostic approach.
Methods: A systematic search was conducted in PubMed, Scopus, and Web of Science up to May 2026, following PRISMA 2020 guidelines. Original studies, systematic reviews, and clinical trials addressing retinal, cutaneous, or neuromuscular biomarkers in patients with Long-COVID and dysautonomia were included.
Results: A total of 48 studies met the eligibility criteria. The reviewed evidence confirms the presence of objective retinal alterations, including thinning of the macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL). Optical coherence tomography angiography (OCTA) has revealed consistent reduction in vessel density. In the cutaneous domain, skin biopsy has demonstrated small fiber neuropathy in 56.5% of cases, affecting both epidermal and autonomic nerve fibers. The presence of cutaneous phosphorylated α-synuclein (p-syn) suggests a shared neuropathological mechanism with synucleinopathies. In the neuromuscular domain, quantitative electromyography (qEMG) and single fiber EMG (SFEMG) studies have documented persistent myopathic alterations and neuromuscular transmission abnormalities. Handgrip strength (HGS) has been identified as an objective marker of functional impairment.
Conclusion: The integration of retinal (OCT/OCTA), cutaneous (skin biopsy, p-syn), and neuromuscular (EMG, SFEMG, HGS) biomarkers enables a multisystem characterization of Long-COVID and post-infectious dysautonomia. This multidisciplinary approach offers opportunities for objective diagnosis, risk stratification, and treatment response monitoring.
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Copyright (c) 2026 Mishell Antonella Román Arévalo, Nicole Tatiana Álvarez Cayambe, Marilyn Estefany Erazo Jaya, Sara Isabel Espinoza Flores, Nicole Stefany Aguilar Sanmartin
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