ABSTRACT
INTRODUCTION: Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. Abnormalities in brain connectivity were found in recovered patients compared to non-infected controls. This study aims to evaluate the effect of hyperbaric oxygen therapy (HBOT) on brain connectivity in post-COVID-19 patients. METHODS: In this randomized, sham-controlled, double-blind trial, 73 patients were randomized to receive 40 daily sessions of HBOT (n = 37) or sham treatment (n = 36). We examined pre- and post-treatment resting-state brain functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) scans to evaluate functional and structural connectivity changes, which were correlated to cognitive and psychological distress measures. RESULTS: The ROI-to-ROI analysis revealed decreased internetwork connectivity in the HBOT group which was negatively correlated to improvements in attention and executive function scores (p < 0.001). Significant group-by-time interactions were demonstrated in the right hippocampal resting state function connectivity (rsFC) in the medial prefrontal cortex (PFWE = 0.002). Seed-to-voxel analysis also revealed a negative correlation in the brief symptom inventory (BSI-18) score and in the rsFC between the amygdala seed, the angular gyrus, and the primary sensory motor area (PFWE = 0.012, 0.002). Positive correlations were found between the BSI-18 score and the left insular cortex seed and FPN (angular gyrus) (PFWE < 0.0001). Tractography based structural connectivity analysis showed a significant group-by-time interaction in the fractional anisotropy (FA) of left amygdala tracts (F = 7.81, P = 0.007). The efficacy measure had significant group-by-time interactions (F = 5.98, p = 0.017) in the amygdala circuit. CONCLUSIONS: This study indicates that HBOT improves disruptions in white matter tracts and alters the functional connectivity organization of neural pathways attributed to cognitive and emotional recovery in post-COVID-19 patients. This study also highlights the potential of structural and functional connectivity analysis as a promising treatment response monitoring tool.
ABSTRACT
Introduction Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. Abnormalities in brain connectivity were found in recovered patients compared to non-infected controls. This study aims to evaluate the effect of hyperbaric oxygen therapy (HBOT) on brain connectivity in post-COVID-19 patients. Methods In this randomized, sham-controlled, double-blind trial, 73 patients were randomized to receive 40 daily sessions of HBOT (n=37) or sham treatment (n=36). We examined pre- and post-treatment resting-state brain functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) scans to evaluate functional and structural connectivity changes, which were correlated to cognitive and psychological distress measures. Results The ROI-to-ROI analysis revealed decreased internetwork connectivity in the HBOT group which was negatively correlated to improvements in attention and executive function scores (p<0.001). Significant group-by-time interactions were demonstrated in the right hippocampal resting state function connectivity (rsFC) in the medial prefrontal cortex (PFWE = 0.002). Seed-to-voxel analysis also revealed a negative correlation in the brief symptom inventory (BSI-18) score and in the rsFC between the amygdala seed, the angular gyrus, and the primary sensory motor area (PFWE = 0.012, 0.002). Positive correlations were found between the BSI-18 score and the left insular cortex seed and FPN (angular gyrus) (PFWE < 0.0001). Tractography based structural connectivity analysis showed a significant group-by-time interaction in the fractional anisotropy (FA) of left amygdala tracts (F= 7.81, P=0.007). The efficacy measure had significant group-by-time interactions (F=5.98, p=0.017) in the amygdala circuit. Conclusions This study indicates that HBOT improves disruptions in white matter tracts and alters the functional connectivity organization of neural pathways attributed to cognitive and emotional recovery in post-COVID-19 patients. This study also highlights the potential of structural and functional connectivity analysis as a promising treatment response monitoring tool.
ABSTRACT
Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. The mechanism can be related to brain tissue pathology caused by virus invasion or indirectly by neuroinflammation and hypercoagulability. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT or HBO2 therapy) on post-COVID-19 patients with ongoing symptoms for at least 3 months after confirmed infection. Seventy-three patients were randomized to receive daily 40 session of HBOT (n = 37) or sham (n = 36). Follow-up assessments were performed at baseline and 1-3 weeks after the last treatment session. Following HBOT, there was a significant group-by-time interaction in global cognitive function, attention and executive function (d = 0.495, p = 0.038; d = 0.477, p = 0.04 and d = 0.463, p = 0.05 respectively). Significant improvement was also demonstrated in the energy domain (d = 0.522, p = 0.029), sleep (d = - 0.48, p = 0.042), psychiatric symptoms (d = 0.636, p = 0.008), and pain interference (d = 0.737, p = 0.001). Clinical outcomes were associated with significant improvement in brain MRI perfusion and microstructural changes in the supramarginal gyrus, left supplementary motor area, right insula, left frontal precentral gyrus, right middle frontal gyrus, and superior corona radiate. These results indicate that HBOT can induce neuroplasticity and improve cognitive, psychiatric, fatigue, sleep and pain symptoms of patients suffering from post-COVID-19 condition. HBOT's beneficial effect may be attributed to increased brain perfusion and neuroplasticity in regions associated with cognitive and emotional roles.
Subject(s)
COVID-19 , Hyperbaric Oxygenation , Brain/diagnostic imaging , COVID-19/complications , COVID-19/therapy , Humans , Hyperbaric Oxygenation/methods , Pain , SARS-CoV-2ABSTRACT
BACKGROUND: The coronavirus disease 2019 pandemic has resulted in a growing population of individuals who experience a wide range of persistent symptoms referred to as "long COVID." Symptoms include neurocognitive impairment and fatigue. Two potential mechanisms could be responsible for these long-term unremitting symptoms: hypercoagulability, which increases the risk of blood vessel occlusion, and an uncontrolled continuous inflammatory response. Currently, no known treatment is available for long COVID. One of the options to reverse hypoxia, reduce neuroinflammation, and induce neuroplasticity is hyperbaric oxygen therapy. In this article, we present the first case report of a previously healthy athletic individual who suffered from long COVID syndrome treated successfully with hyperbaric oxygen therapy. CASE PRESENTATION: A previously healthy 55-year-old Caucasian man presented 3 months after severe coronavirus disease 2019 infection with long COVID syndrome. His symptoms included a decline in memory, multitasking abilities, energy, breathing, and physical fitness. After evaluation that included brain perfusion magnetic resonance imaging, diffusion tensor imaging, computerized cognitive tests, and cardiopulmonary test, he was treated with hyperbaric oxygen therapy. Each session included exposure to 90 minutes of 100% oxygen at 2 atmosphere absolute pressure with 5-minute air breaks every 20 minutes for 60 sessions, 5 days per week. Evaluation after completing the treatment showed significant improvements in brain perfusion and microstructure by magnetic resonance imaging and significant improvement in memory with the most dominant effect being on nonverbal memory, executive functions, attention, information procession speed, cognitive flexibility, and multitasking. The improved cognitive functions correlated with the increased cerebral blood flow in brain regions as measured by perfusion magnetic resonance imaging. With regard to physical capacity, there was a 34% increase in the maximum rate of oxygen consumed during exercise and a 44% improvement in forced vital capacity. The improved physical measurements correlated with the regain of his pre-COVID physical capacity. CONCLUSIONS: We report the first case of successfully treated long COVID symptoms with hyperbaric oxygen therapy with improvements in cognition and cardiopulmonary function. The beneficial effects of hyperbaric oxygen shed additional light on the pathophysiology of long COVID. As this is a single case report, further prospective randomized control studies are needed.