Potential of Nano-Antioxidants and Nanomedicine for Recovery from Neurological Disorders Linked to Long COVID Syndrome

Long-term neurological complications, persisting in patients who cannot fully recover several months after severe SARS-CoV-2 coronavirus infection, are referred to as neurological sequelae of the long COVID syndrome. Among the numerous clinical post-acute COVID-19 symptoms, neurological and psychiatric manifestations comprise prolonged fatigue, brain fog, memory deficits, headache, ageusia, anosmia, myalgias, cognitive impairments, anxiety, and depression lasting several months. Considering that neurons are highly vulnerable to inflammatory and oxidative stress damages following the overproduction of reactive oxygen species (ROS), neuroinflammation and oxidative stress have been suggested to dominate the pathophysiological mechanisms of the long COVID syndrome. It is emphasized that mitochondrial dysfunction and oxidative stress damages are crucial for the pathogenesis of neurodegenerative disorders. Importantly, antioxidant therapies have the potential to slow down and prevent disease progression. However, many antioxidant compounds display low bioavailability, instability, and transport to targeted tissues, limiting their clinical applications. Various nanocarrier types, e.g., liposomes, cubosomes, solid lipid nanoparticles, micelles, dendrimers, carbon-based nanostructures, nanoceria, and other inorganic nanoparticles, can be employed to enhance antioxidant bioavailability. Here, we highlight the potential of phytochemical antioxidants and other neuroprotective agents (curcumin, quercetin, vitamins C, E and D, melatonin, rosmarinic acid, N-acetylcysteine, and Ginkgo Biloba derivatives) in therapeutic strategies for neuroregeneration. A particular focus is given to the beneficial role of nanoparticle-mediated drug-delivery systems in addressing the challenges of antioxidants for managing and preventing neurological disorders as factors of long COVID sequelae.

Automated summary

Long-term neurological complications, referred to as long COVID syndrome, include symptoms such as prolonged fatigue, memory deficits, headache, and anxiety, which continue for several months after severe SARS-CoV-2 infection. Neuroinflammation and oxidative stress are believed to be the dominant mechanisms in the pathophysiology of this syndrome. Mitochondrial dysfunction and oxidative stress are important factors in the development of neurodegenerative disorders. Antioxidant therapies have potential, but their bioavailability and transport to targeted tissues are limited. Nanocarriers can enhance antioxidant bioavailability, and phytochemical antioxidants and neuroprotective agents show promise in therapeutic strategies for neuroregeneration. Nanoparticle-mediated drug-delivery systems are highlighted for addressing the challenges of antioxidants in managing and preventing neurological disorders associated with long COVID sequelae.