Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial

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.

Figure 1

Questionnaire results analysis shown in violin plots of actual distribution, and in boxplots. Values are normalized to answer scale range: SF-36, Energy [0..100], PSQI, Global [0..21], BSI-18, Total [0..72] and BPI, Pain Interference [0..10]. The red mark indicates the median, and the bottom and top edges of the box indicate the 25th and 75th percentiles, respectively. Black marks indicate mean and standard deviation. ^†p < 0.0001, N.S. not significant (see also Table 3).

Figure 2

Brain regions with significant post-hyperbaric oxygen therapy changes compared to control. Group-by-time interaction ANOVA model in: (A) cerebral blood flow (CBF) in GM, p < 0.0005, uncorrected, (B) mean diffusivity DTI-MD in GM, p < 0.002, uncorrected, (C) fractional anisotropy DTI-FA in WM, p < 0.002, uncorrected. (D) significant correlation between pain interference score and the right middle formal gyrus MD (BA8). (E) significant correlation between the energy score and the right middle frontal gyrus MD (BA10). r is Pearson's correlation coefficient. The 95% prediction interval is presented in the shaded area. CBF cerebral blood flow, MD mean diffusivity, FA fractional anisotropy, GM gray matter, WM white matter, R right, L left, BA Brodmann area. (A) and (B) brain images were created using BrainNet Viewer software (http://www.nitrc.org/projects/bnv/). (C) Brain image was created using ExploreDTI software (https://www.exploredti.com/).