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The long-term effects of COVID-19 on brain structure remain unclear. A prospective study was conducted to explore the changes in brain structure in COVID-19 survivors at one and two years after discharge (COVID-19one, COVID-19two). The difference in gray matter volume (GMV) was analyzed using the voxel-based morphometry method, and correlation analyses were conducted. The dynamic changes in clinical sequelae varied. The GMVs in the cerebellum and vermis were reduced in COVID-19one and COVID-19two, positively correlated with lymphocyte count, and negatively correlated with neutrophil count, neutrophil/lymphocyte ratio (COVID-19one), and systemic immune-inflammation index (COVID-19two). The decreased GMVs in the left middle frontal gyrus, inferior frontal gyrus of the operculum, right middle temporal gyrus, and inferior temporal gyrus returned to normal in COVID-19two. The decreased GMV in the left frontal lobe was negatively correlated with the Athens Insomnia Scale (AIS). The GMV in the left temporal lobe was aggravated in COVID-19two and positively correlated with C-reactive protein. In conclusion, GMV recovery coexisted with injury, which was associated with AIS and inflammatory factors. This may shed some light on the dynamic changes in brain structure and the possible predictors that may be related to GMV changes in COVID-19two.
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Introduction: Occupational burnout has become a pervasive problem in human services. Medical professionals are particularly vulnerable to burnout, which may lead to reduced motivation, medical errors, and voluntary absenteeism. To ensure effect functioning of medical systems, better understanding of burnout among medical professionals is warranted. Objective(s): We aimed to investigate the structural brain correlates of burnout severity among medical professionals. Method(s): Nurses in active service underwent structural magnetic resonance imaging. We assessed their burnout severity using self-reported psychological questionnaires. This study was approved by the Committee on Medical Ethics of Kyoto University and was conducted in accordance with the Code of Ethics of the World Medical Association. Result(s): The results reflected considerable individual differences in burnout severity in our sample. Our findngs revealed that the levels of burnout severity were associated with the regional gray matter volumes in brain areas such as ventromedial prefrontal cortex and insula. Conclusion(s): Since the outbreak of the COVID-19 pandemic, medical professionals have faced even greater stress. We hope that our findings will contribute to a better understanding of the mechanisms of burnout and offer useful insights for developing effective interventions to manage stress and burnout.
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Introduction Neuropsychiatric symptoms are among the most common sequelae of long-COVID-19 and highly diminish the patient's quality of life. As accumulating evidence suggests an impact of survived SARS-CoV-2-infection on brain physiology, it appears necessary to further investigate brain structural changes in relation to clinical long-COVID symptoms. Understanding the pathogenic processes in neuropsychiatric long-COVID will be vital to identify targeted therapy and to ease the months long-lasting symptoms. Methods The present cross-sectional study investigated 3T-MRI scans from long-COVID patients (n=30) with neuropsychiatric symptoms, and healthy controls matched for age and gender (n=20). Whole-brain comparison of grey matter volume (GMV) was conducted by voxel-based morphometry using the CAT12 software package. To determine whether changes in GMV are predicted by neuropsychiatric symptom burden and / or initial severity of symptoms of COVID19 and time since onset of COVID-19, we performed multiple linear regression analysis. Results Enlarged GMV in long-COVID patients was present in several clusters (p<0.05, FWE- corr-ected) spanning frontotemporal areas, insula, hippocampus, amygdala, basal ganglia, and thalamus in both hemispheres when compared to controls. Time since onset of COVID-19 was a significant regressor in three of these clusters (anatomically located in right inferior frontal gyrus, lateral and posterior orbital gyrus, anterior parts of the insula, left superior, middle and inferior temporal gyrus and left postcentral and precentral gyrus). Conclusion Grey matter alterations in limbic and secondary olfactory areas are present in neuropsychiatric long-COVID patients. Some GMV alterations were inversely associated with time elapsed since acute COVID-19, suggesting higher GMV with shorter time since onset of COVID-19. Detection of associations between GMV and clinical symptoms might be difficult, because of heterogenous clinical presentation. Larger samples and longitudinal data in neuropsychiatric long-COVID patients are required to further clarify the mediating mechanisms between COVID-19 and GMV.
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Background: Growing evidence suggests that the central nervous system is affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), since infected patients suffer from acute and long-term neurological sequelae. Nevertheless, it is currently unknown whether the virus affects the brain cortex. The purpose of this study was to assess the cortical gray matter volume, the cortical thickness, and the cortical surface area in a group of SARS-CoV-2 infected patients with neurological symptoms compared to healthy control subjects. Additionally, we analyzed the cortical features and the association with inflammatory biomarkers in the cerebrospinal fluid (CSF) and plasma. Materials and methods: Thirty-three patients were selected from a prospective cross-sectional study cohort during the ongoing pandemic (August 2020-April 2021) at the university hospitals of Basel and Zurich (Switzerland). The group included patients with different neurological symptom severity (Class I: nearly asymptomatic/mild symptoms, II: moderate symptoms, III: severe symptoms). Thirty-three healthy age and sex-matched subjects that underwent the same MRI protocol served as controls. For each anatomical T1w MPRAGE image, regional cortical gray matter volume, thickness, and surface area were computed with FreeSurfer. Using a linear regression model, cortical measures were compared between groups (patients vs. controls; Class I vs. II-III), with age, sex, MRI magnetic field strength, and total intracranial volume/mean thickness/total surface area as covariates. In a subgroup of patients, the association between cortical features and clinical parameters was assessed using partial correlation adjusting for the same covariates. P-values were corrected using a false discovery rate (FDR). Results: Our findings revealed a lower cortical volume in COVID-19 patients' orbitofrontal, frontal, and cingulate regions than in controls (p < 0.05). Regional gray matter volume and thickness decreases were negatively associated with CSF total protein levels, the CSF/blood-albumin ratio, and CSF EN-RAGE levels. Conclusion: Our data suggest that viral-triggered inflammation leads to neurotoxic damage in some cortical areas during the acute phase of a COVID-19 infection in patients with neurological symptoms.
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Background: A high prevalence of depression, anxiety, insomnia and PTSD has been reported in COVID-19 survivors [1]. This is similar to what previously observed in other Coronavirus-related diseases such as SARS and MERS [2]. The pathophysiology of post-infection neuropsychiatric symptoms is likely to be multifactorial, with a role played by inflammatory and immunological factors [3], but it is still largely unknown;we thus investigated COVID-19 survivors via 3T MRI imaging to identify neural underpinnings of post-infection neuropsychiatric symptoms in order to further elucidate their complex pathophysiology. Methods: Covid-19 survivors were recruited during an ongoing prospective cohort study at IRCCS San Raffaele Hospital in Milan;psychopathology was initially measured via several self-report questionnaires (Impact of Events Scale-Revised (IES-R), Zung Self-Rating Depression Scale (ZSDS), 13-item Beck's Depression Inventory (BDI));subsequently patients (n=28) underwent 3T MRI scanning (Philips 3T Ingenia CX scanner with 32-channel sensitivity encoding SENSE head coil). T1 weighted images were processed using Computational Anatomy Toolbox (CAT12) for Statistical Parametric Mapping 12 (SPM12) in Matlab R2016b;segmentation into Gray Matter, White Matter and cerebrospinal fluid, bias regularization, non-linear modulation and normalization to MNI space were performed;measures of Total Intracranial Volume (TIV) were obtained and images were smoothed with an 8-mm full width at half maximum Gaussian filter. Multiple regressions were performed using SPM12 software package: with no a priori regions of interest selected, whole-brain gray matter volumes were used as dependent variables, psychometric scales scores as independent variables, and age, sex and TIV as nuisance covariates. Results: After VBM regression analysis covarying for age, sex and TIV, ZSDS Index scores were inversely correlated with gray matter volume in the Bilateral Anterior Cingulate Cortex (MNI 2, 24, 28, cluster level pFWE = 0.045, k=767);furthermore 3 cluster were identified comprising again the anterior cingulate cortex and the insular cortex bilaterally in which IES-R scores were inversely correlated with gray matter volumes (Cluster 1: MNI -30, 9, 3, cluster level pFWE = 0.005, k=1284;Cluster 2: MNI 36, -3, -3, cluster level pFWE = 0.037, k=773;Cluster 3: MNI 9, 30, 28, cluster level pFWE = 0.038, k=766). No other statistical significant result was found. Conclusions: Our study identified an inverse correlation between anterior cingulate cortex volumes and depressive symptomatology, measured via ZSDS, and between bilateral insulae and anterior cingulate cortex volumes and the degree of distress in response to the traumatic event, measured via the IES-R. Analogous findings have already been reported in patients with Major depression [4] and PTSD [5], and our study confirms the role of volumetric reductions of these brain regions in depressive and post-traumatic symptomatology. Given the nature of our study it is not possible to infer whether the reduction of gray matter volume is a consequence of the Covid-19 infection itself or, as it appears more likely, precede the infection acting as predisposing factor for the subsequent development of depressive and post-traumatic symptomatology. No conflict of interest
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BACKGROUND: Increasing evidence supported the possible neuro-invasion potential of SARS-CoV-2. However, no studies were conducted to explore the existence of the micro-structural changes in the central nervous system after infection. We aimed to identify the existence of potential brain micro-structural changes related to SARS-CoV-2. METHODS: In this prospective study, diffusion tensor imaging (DTI) and 3D high-resolution T1WI sequences were acquired in 60 recovered COVID-19 patients (56.67% male; age: 44.10 ± 16.00) and 39 age- and sex-matched non-COVID-19 controls (56.41% male; age: 45.88 ± 13.90). Registered fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were quantified for DTI, and an index score system was introduced. Regional volumes derived from Voxel-based Morphometry (VBM) and DTI metrics were compared using analysis of covariance (ANCOVA). Two sample t-test and Spearman correlation were conducted to assess the relationships among imaging indices, index scores and clinical information. FINDINGS: In this follow-up stage, neurological symptoms were presented in 55% COVID-19 patients. COVID-19 patients had statistically significantly higher bilateral gray matter volumes (GMV) in olfactory cortices, hippocampi, insulas, left Rolandic operculum, left Heschl's gyrus and right cingulate gyrus and a general decline of MD, AD, RD accompanied with an increase of FA in white matter, especially AD in the right CR, EC and SFF, and MD in SFF compared with non-COVID-19 volunteers (corrected p value <0.05). Global GMV, GMVs in left Rolandic operculum, right cingulate, bilateral hippocampi, left Heschl's gyrus, and Global MD of WM were found to correlate with memory loss (p value <0.05). GMVs in the right cingulate gyrus and left hippocampus were related to smell loss (p value <0.05). MD-GM score, global GMV, and GMV in right cingulate gyrus were correlated with LDH level (p value <0.05). INTERPRETATION: Study findings revealed possible disruption to micro-structural and functional brain integrity in the recovery stages of COVID-19, suggesting the long-term consequences of SARS-CoV-2. FUNDING: Shanghai Natural Science Foundation, Youth Program of National Natural Science Foundation of China, Shanghai Sailing Program, Shanghai Science and Technology Development, Shanghai Municipal Science and Technology Major Project and ZJ Lab.
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BACKGROUND: Evidence has suggested that exercise protects against cognitive decline in aging, but the recent lockdown measures associated with the COVID-19 pandemic have limited the opportunity for outdoor exercise. Herein we tested the effects of an indoor exercise, Qigong, on neurocognitive functioning as well as its potential neuro-immune pathway. METHODS: We conducted a 12-week randomized active-controlled trial with two study arms in cognitively healthy older people. We applied Wu Xing Ping Heng Gong (Qigong), which was designed by an experienced Daoist Qigong master, to the experimental group, whereas we applied the physical stretching exercise to the control group. The Qigong exercise consisted of a range of movements involving the stretching of arms and legs, the turning of the torso, and relaxing, which would follow the fundamental principles of Daoism and traditional Chinese medicine (e.g., Qi). We measured aging-sensitive neurocognitive abilities, serum interleukin-6 (IL-6) levels, and brain structural volumes in the experimental (Qigong, n = 22) and control groups (stretching, n = 26) before and after the 12-week training. RESULTS: We observed that Qigong caused significant improvement in processing speed (t (46) = 2.03, p = 0.048) and sustained attention (t (46) = -2.34, p = 0.023), increased hippocampal volume (t (41) = 3.94, p < 0.001), and reduced peripheral IL-6 levels (t (46) = -3.17, p = 0.003). Moreover, following Qigong training, greater reduction of peripheral IL-6 levels was associated with a greater increase of processing speed performance (bootstrapping CI: [0.16, 3.30]) and a more significant training-induced effect of hippocampal volume on the improvement in sustained attention (bootstrapping CI: [-0.35, -0.004]). CONCLUSION: Overall, these findings offer significant insight into the mechanistic role of peripheral IL-6-and its intricate interplay with neural processes-in the beneficial neurocognitive effects of Qigong. The findings have profound implications for early identification and intervention of older individuals vulnerable to cognitive decline, focusing on the neuro-immune pathway. The trial was registered at clinicaltrials.gov (identifier: NCT04641429).
Subject(s)
COVID-19 , Qigong , Aged , Cognition , Communicable Disease Control , Hippocampus , Humans , Interleukin-6 , Pandemics , SARS-CoV-2ABSTRACT
COVID-19, the infectious disease caused by the most recently discovered severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global pandemic. It dramatically affects people's health and daily life. Neurological complications are increasingly documented for patients with COVID-19. However, the effect of COVID-19 on the brain is less studied, and existing quantitative neuroimaging analyses of COVID-19 were mainly based on the univariate voxel-based morphometry analysis (VBM) that requires corrections for a large number of tests for statistical significance, multivariate approaches that can reduce the number of tests to be corrected have not been applied to study COVID-19 effect on the brain yet. In this study, we leveraged source-based morphometry (SBM) analysis, a multivariate extension of VBM, to identify changes derived from computed tomography scans in covarying gray matter volume patterns underlying COVID-19 in 120 neurological patients (including 58 cases with COVID-19 and 62 patients without COVID-19 matched for age, gender and diseases). SBM identified that lower gray matter volume (GMV) in superior/medial/middle frontal gyri was significantly associated with a higher level of disability (modified Rankin Scale) at both discharge and six months follow-up phases even when controlling for cerebrovascular diseases. GMV in superior/medial/middle frontal gyri was also significantly reduced in patients receiving oxygen therapy compared to patients not receiving oxygen therapy. Patients with fever presented significant GMV reduction in inferior/middle temporal gyri and fusiform gyrus compared to patients without fever. Patients with agitation showed GMV reduction in superior/medial/middle frontal gyri compared to patients without agitation. Patients with COVID-19 showed no significant GMV differences from patients without COVID-19 in any brain region. Results suggest that COVID-19 may affect the frontal-temporal network in a secondary manner through fever or lack of oxygen.