Skip to content
Review Open access

Exercise and brain health in long COVID: mechanisms and therapeutic implications for neuropsychiatric disorders

Jul 2026 · Exploration of Neuroscience · 0 citations · 117 references

TL;DR

Clinical evidence suggests that structured, individualized, and supervised exercise programs may improve mood, cognition, mobility, fatigue, fatigue, and quality of life in individuals with long COVID; however, careful pacing and symptom-contingent adaptation are essential in long COVID to avoid post-exertional symptom exacerbation.

Abstract

Psychiatric and neurological disorders represent a major global health burden, often characterized by chronic disability and incomplete response to pharmacological treatments. The emergence of long COVID has further contributed to this challenge, introducing persistent neuropsychiatric and neurological sequelae, including cognitive impairment, fatigue, mood disturbances, and autonomic dysfunction, that overlap with mechanisms observed in established brain disorders. This narrative review synthesizes current evidence on exercise as a multimodal therapeutic strategy for individuals with long COVID and pre-existing or COVID-related psychiatric and neurological conditions. Exercise may exert broad effects across interconnected biological systems, potentially enhancing neuroplasticity and neurotrophic signaling, modulating neuroinflammation and immune responses, improving mitochondrial function and energy metabolism, supporting cerebrovascular health, regulating stress physiology and autonomic balance, and influencing the gut–brain axis. These mechanisms are thought to converge on shared pathophysiological pathways implicated in depression, anxiety, bipolar disorder, schizophrenia, post-traumatic stress disorder, neurodegenerative diseases, stroke, epilepsy, and post-viral syndromes. Clinical evidence suggests that structured, individualized, and supervised exercise programs may improve mood, cognition, mobility, fatigue, and quality of life. However, careful pacing and symptom-contingent adaptation are essential in long COVID to avoid post-exertional symptom exacerbation. Although high-quality randomized trials remain limited, exercise appears to be a promising, low-risk, and potentially scalable component of multidisciplinary rehabilitation in long COVID-related brain disorders.

Read PDF

Similar papers

Review Open access Aug 2026

Long COVID and Mental Health: Neurobiological Mechanisms, Clinical Manifestations, and Treatment Challenges

Background: Long COVID is a heterogeneous multisystem condition associated with fatigue, cognitive difficulties, sleep disturbance, depression, anxiety, and post-traumatic symptoms. Methods: This narrative review examined PubMed/MEDLINE literature published between January 2020 and July 2026, supplemented by major reviews and guidance from WHO, NICE, and CDC. Results: Neuropsychiatric symptoms likely result from interacting mechanisms, including persistent immune activation, autoimmunity, endothelial dysfunction, blood–brain barrier disruption, dysautonomia, altered neurotransmitter metabolism, microbiome changes, and impaired cellular energy production. Routine investigations may be normal, and no diagnostic biomarker has been validated. Treatment remains multidisciplinary, symptom-based, and tailored to clinical phenotype, with rehabilitation adapted for post-exertional malaise. Conclusion: Long COVID requires integrated medical, neurological, and psychiatric assessment. Further biomarker-based research and well-designed clinical trials are needed.

Sandra Kołodziejczyk, Bartłomiej Wiak, Monika Łapot et al. · 0 citations
Review Open access Aug 2026

Molecular and Cellular Mechanisms Linking Mood Disorders, HPA Axis Dysregulation, and Neurocognitive Inflammation to Perioperative Neurocognitive Disorders

Patients with preexisting mood disorders may enter surgery in a biologically sensitized neuroimmune state, lowering the threshold for exaggerated neuroinflammatory responses and postoperative cognitive dysfunction, according to a review of convergent pathophysiologic pathways.

Alyson Sato, N. Chang, N. Knezevic et al. · 0 citations
Review Aug 2026

Neuroinflammatory pathways linking pain and rehabilitation outcomes in schizophrenia: a narrative review.

A narrative review examines clinical, preclinical, and translational studies addressing the role of neuroinflammation in schizophrenia, with a specific focus on microglial and astrocytic activation, cytokine signaling, oxidative stress pathways, and their interactions with central pain processing circuits.

Sanaz Sedghi Esfahani, Elmira Mahdinia, Setareh Dehkhodaei et al. · 0 citations
Review Open access Sep 2026

Neurobiological and Neuroimmune Mechanisms Linking Chronic Pain, Sleep Disturbances and Mental Health Disorders

Chronic pain, sleep disturbances, and mental health disorders such as anxiety and depression disorders frequently co-occur, forming a self-reinforcing cycle that impairs daily functioning and quality of life. Chronic pain is driven by peripheral and central sensitization, the latter sustained by reciprocal microglial–astrocytic crosstalk and maladaptive neuroplasticity. Poor sleep amplifies pain through inflammation and circadian disruption. Imbalances in serotonin, dopamine, and norepinephrine, together with limbic alterations and HPA axis dysregulation, contribute to comorbid anxiety and depression. Elevated pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α), NF-κB-driven neuroinflammation, and mitochondrial oxidative stress serve as key molecular links. Building on previous evidence, this review presents an updated triadic, mechanism-based framework describing the reciprocal reinforcement among chronic pain, sleep disturbances, and anxiety and depressive disorders. Consequently, therapeutic strategies targeting inflammatory cytokines, microglial and astrocytic activation, neurotransmitter imbalance, and psychological dysfunction may help address these shared neuroimmune and neuroplastic mechanisms underlying these interconnected disorders.

Boris Burnjaković, Harrison Moy, Aleksandar Sič et al. · 0 citations

We use cookies to run the site and, with your consent, for analytics and to show ads. See our Cookie Policy.