Two-year follow-up of brain structural changes in patients who recovered from COVID-19: A prospective study

Du, Yanyao; Zhao, Wei; Huang, Shuqiang; Huang, Yijie; Chen, Yanjing; Zhang, Huiting; Guo, Hu; Li, Jun

doi:10.1016/j.psychres.2022.114969

Cited by 23 publications

(29 citation statements)

References 36 publications

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“…190 potential subjects were identified, and thirty-three subjects (17 female) who were previously diagnosed with COVID-19 were eventually enrolled between January 2021 and June 2022. Inclusion criteria were: (1) being between the ages of 18-80, (2) meeting CDC guidelines for discontinuation of home isolation and being at least 6 weeks post-quarantine; (3) having the ability to read, write, speak, and understand English, as well as comprehension of the protocol; (4) confirming the COVID-19 diagnosis via medical record; and (5) experiencing or not experiencing PCS symptoms (depending on group assignment), according to the Chalder Fatigue Scale CFQ-11 (PCS fatigue ≥ 5 [6,22]; completed via email or phone). Exclusion criteria were: (1) history of traumatic brain injury or hydrocephalus; (2) pregnancy;…”

Section: Subjectsmentioning

confidence: 99%

“…Initially, the focus of physicians and researchers was on acute symptoms and care. However, three years into the pandemic, more focus has been put on the long-term outcomes of COVID-19 infection [ 1 , 2 ], particularly the prevalence of post-COVID-19 syndrome (PCS) symptoms. PCS is characterized as symptoms that last for at least two months after an acute COVID-19 illness and cannot be explained by an alternate diagnosis (WHO).…”

Section: Introductionmentioning

confidence: 99%

“…Regardless of the source (i.e., direct or indirect invasion), it has been proposed that brain morphometrical alterations could arise from several factors, such as decreased sensory input (e.g., dysosmia) or chronic inflammation [ 10 , 12 ]. Recent studies have investigated morphometric changes over time in the brain after acute COVID-19 and reported mixed results [ 1 , 2 , 12 , 13 ]. Specifically, Douaud et al showed greater rates of atrophy of certain olfactory and limbic regions in PCS patients ~5 months post-infection compared to healthy controls, but no association between time since infection and brain volume was demonstrated [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, despite variability in brain volumes at different time points, both Tian et al and Besteher et al found inverse associations between volume and time, with volume decreasing over time [ 2 , 13 ]. Additionally, Du et al compared brain regional volumes at 1 and 2 years after COVID-19 infection, finding persistently smaller volumes in deeper brain regions but recovered volumes in frontal and temporal areas at year 2 compared to year 1 [ 1 ]. These studies suggest that acute COVID-19 may influence cerebral volumes up to 2 years post-infection [ 1 ], although more research is needed to clarify some of the conflicting reports and to fully delineate the timeline of possible effects.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, Du et al compared brain regional volumes at 1 and 2 years after COVID-19 infection, finding persistently smaller volumes in deeper brain regions but recovered volumes in frontal and temporal areas at year 2 compared to year 1 [ 1 ]. These studies suggest that acute COVID-19 may influence cerebral volumes up to 2 years post-infection [ 1 ], although more research is needed to clarify some of the conflicting reports and to fully delineate the timeline of possible effects. The inconsistency in results may be due to the lack of investigations focusing on the effects of PCS after mild (i.e., not hospitalized) COVID-19 infection on brain morphometry over time, especially comparing post-acute (1–6 months post-infection) phases versus chronic (>6 months post-infection).…”

Section: Introductionmentioning

confidence: 99%

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Effect of Post-COVID-19 on Brain Volume and Glucose Metabolism: Influence of Time Since Infection and Fatigue Status

et al. 2023

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Post-COVID-19 syndrome (PCS) fatigue is typically most severe <6 months post-infection. Combining magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging with the glucose analog [18F]-Fluorodeoxyglucose (FDG) provides a comprehensive overview of the effects of PCS on regional brain volumes and metabolism, respectively. The primary purpose of this exploratory study was to investigate differences in MRI/PET outcomes between people < 6 months (N = 18, 11 female) and > 6 months (N = 15, 6 female) after COVID-19. The secondary purpose was to assess if any differences in MRI/PET outcomes were associated with fatigue symptoms. Subjects > 6 months showed smaller volumes in the putamen, pallidum, and thalamus compared to subjects < 6 months. In subjects > 6 months, fatigued subjects had smaller volumes in frontal areas compared to non-fatigued subjects. Moreover, worse fatigue was associated with smaller volumes in several frontal areas in subjects > 6 months. The results revealed no brain metabolism differences between subjects > 6 and < 6 months. However, both groups exhibited both regional hypo- and hypermetabolism compared to a normative database. These results suggest that PCS may alter regional brain volumes but not metabolism in people > 6 months, particularly those experiencing fatigue symptoms.

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Section: Subjectsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Effect of Post-COVID-19 on Brain Volume and Glucose Metabolism: Influence of Time Since Infection and Fatigue Status

et al. 2023

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Gray Matter Thickness and Subcortical Nuclear Volume in Men After SARS-CoV-2 Omicron Infection

Du,

Zhao,

Huang

et al. 2023

JAMA Netw Open

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ImportanceThe clinical manifestations and effects on the brain of the SARS-CoV-2 Omicron variant in the acute postinfection phase remain unclear.ObjectiveTo investigate the pathophysiological mechanisms underlying clinical symptoms and changes to gray matter and subcortical nuclei among male patients after Omicron infection and to provide an imaging basis for early detection and intervention.Design, Setting, and ParticipantsIn this cohort study, a total of 207 men underwent health screening magnetic resonance imaging scans between August 28 and September 18, 2022; among them, 98 provided complete imaging and neuropsychiatric data. Sixty-one participants with Omicron infection were reevaluated after infection (January 6 to 14, 2023). Neuropsychiatric data, clinical symptoms, and magnetic resonance imaging data were collected in the acute post-Omicron period, and their clinical symptoms were followed up after 3 months. Gray matter indexes and subcortical nuclear volumes were analyzed. Associations between changes in gray matter and neuropsychiatric data were evaluated with correlation analyses.ExposuresGray matter thickness and subcortical nuclear volume change data were compared before and after Omicron infection.Main Outcomes and MeasuresThe gray matter indexes and subcutaneous nuclear volume were generated from the 3-dimensional magnetization-prepared rapid acquisition gradient echo and were calculated with imaging software.ResultsNinety-eight men underwent complete baseline data collection; of these, 61 (mean [SD] age, 43.1 [9.9] years) voluntarily enrolled in post-Omicron follow-up and 17 (mean [SD] age, 43.5 [10.0] years) voluntarily enrolled in 3-month follow-up. Compared with pre-Omicron measures, Beck Anxiety Inventory scores were significantly increased (median, 4.50 [IQR, 1.00-7.00] to 4.00 [IQR, 2.00-9.75]; P = .006) and depressive distress scores were significantly decreased (median, 18.00 [IQR, 16.00-20.22] to 16.00 [IQR, 15.00-19.00]; P = .003) at the acute post-Omicron follow-up. Fever, headache, fatigue, myalgia, cough, and dyspnea were the main symptoms during the post-Omicron follow-up; among the participants in the 3-month follow-up, fever (11 [64.7%] vs 2 [11.8%]; P = .01), myalgia (10 [58.8%] vs 3 (17.6%]; P = .04), and cough (12 [70.6%] vs 4 [23.5%]; P = .02) were significantly improved. The gray matter thickness in the left precuneus (mean [SD], 2.7 [0.3] to 2.6 [0.2] mm; P &lt; .001) and right lateral occipital region (mean [SD], 2.8 [0.2] to 2.7 [0.2] and 2.5 [0.2] to 2.5 [0.2] mm; P &lt; .001 for both) and the ratio of the right hippocampus volume to the total intracranial volume (mean [SD]. 0.003 [0.0003] to 0.003 [0.0002]; P = .04) were significantly reduced in the post-Omicron follow-up. The febrile group had reduced sulcus depth of the right inferior parietal region compared with the nonfebrile group (mean [SD], 3.9 [2.3] to 4.8 [1.1]; P = .048. In the post-Omicron period, the thickness of the left precuneus was negatively correlated with the Beck Anxiety Inventory scores (r = −0.39; P = .002; false discovery rate P = .02), and the ratio of the right hippocampus to the total intracranial volume was positively correlated with the Word Fluency Test scores (r = 0.34; P = .007).Conclusions and RelevanceIn this cohort study of male patients infected with the Omicron variant, the duration of symptoms in multiple systems after infection was short. Changes in gray matter thickness and subcortical nuclear volume injury were observed in the post-Omicron period. These findings provide new insights into the emotional and cognitive mechanisms of an Omicron infection, demonstrate its association with alterations to the nervous system, and verify an imaging basis for early detection and intervention of neurological sequelae.

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MRI evidence of gray matter loss in COVID‐19 patients with cognitive and olfactory disorders

Capelli,

Arrigoni,

Napolitano

et al. 2024

Ann Clin Transl Neurol

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ObjectiveThe aim of this study was to assess COVID‐19‐related gray matter (GM) structural alterations in two distinct groups of patients presenting with the prevailing and distinctive COVID‐19‐related neurological symptoms – isolated olfactory disorders as sole neurological manifestation (COVID‐OD) and cognitive disorders (COVID‐CD) – as compared to a control group of unaffected individuals.MethodsThe study included 61 COVID‐CD patients (57 [60–63] years, 62% females), 84 COVID‐OD patients (49 [35–57] years, 60% females), and 17 controls (51 [41–52] years, 41% females). Region‐based morphometry (RBM) and voxel‐based morphometry (VBM) were performed on T1‐weighted MRI scans to assess GM regional volume and voxel‐wise density differences between COVID‐19 patients and controls. Surface‐based morphometry (SBM) was applied to investigate cortical thickness alterations. The statistical models built to assess GM structural differences among groups included total intracranial volume and age as nuisance variables.ResultsThe multi‐morphometric analysis revealed statistically significant (p < 0.05 corrected for multiple comparisons) reduction in GM regional volumes, in voxel‐wise GM density and in cortical thickness in both COVID‐CD and COVID‐OD patient groups as compared to controls. Across all three analyses, COVID‐CD patients showed more distributed and severe GM loss than COVID‐OD patients. The most prominently affected GM regions in the COVID‐CD group included the hippocampus, putamen, cingulate gyrus, precuneus, precentral and postcentral gyri, amygdala, lingual gyrus, and caudate nucleus.InterpretationOur MRI findings show that COVID‐19‐related olfactory and cognitive disorders both induce GM atrophy, although at different degrees of severity, likely indicative of neurodegeneration and neuroinflammation.

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Two-year follow-up of brain structural changes in patients who recovered from COVID-19: A prospective study

Cited by 23 publications

References 36 publications

Effect of Post-COVID-19 on Brain Volume and Glucose Metabolism: Influence of Time Since Infection and Fatigue Status

Effect of Post-COVID-19 on Brain Volume and Glucose Metabolism: Influence of Time Since Infection and Fatigue Status

Gray Matter Thickness and Subcortical Nuclear Volume in Men After SARS-CoV-2 Omicron Infection

MRI evidence of gray matter loss in COVID‐19 patients with cognitive and olfactory disorders

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