Alterations of frontal-temporal gray matter volume associate with clinical measures of older adults with COVID-19

Duan, Kuaikuai; Premi, Enrico; Padovani, Alessandro; Cristillo, Viviana; Benussi, Alberto; Libri, Ilenia; Giunta, Marcello; Bockholt, H. Jeremy; Liu, Jingyu; Campora, Riccardo Alberto; Pezzini, Alessandro; Gasparotti, Roberto; Magoni, Mauro; Padovani, Alessandro; Calhoun, Vince D.

doi:10.1016/j.ynstr.2021.100326

Cited by 53 publications

(50 citation statements)

References 68 publications

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“…A decrease in cortical thickness and changes in white matter microstructure were more profound and extensive in the severe than in the asymptomatic group, particularly in the frontal and temporal systems bilaterally, but without clear side predisposition in our preliminary cohort. The observed decreased frontal and temporal grey matter brain volumes of patients with severe COVID-19 compared with those of healthy subjects and asymptomatic patients is consistent with other reports of grey matter brain volume loss, even among COVID-19 remitted patients and those with asymptomatic courses [ 67 ].…”

Section: Discussionsupporting

confidence: 91%

Longitudinal Neurocognitive and Pulmonological Profile of Long COVID-19: Protocol for the COVIMMUNE-Clin Study

Widmann¹,

Wieberneit²,

Bieler³

et al. 2021

JMIR Res Protoc

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Background There is a dearth of information about “brain fog,” characterized by concentration, word-finding, or memory problems, which has been listed in the new World Health Organization provisional classification “U09.9 Post-COVID-19 Condition.” Moreover, the extent to which these symptoms may be associated with neurological, pulmonary, or psychiatric difficulties is unclear. Objective This ongoing cohort study aims to carefully assess neurocognitive function in the context of the neurological, psychiatric, and pulmonary sequelae of SARS-CoV-2 infection among patients with asymptomatic/mild and severe cases of COVID-19 after remission, including actively recruited healthy controls. Methods A total of 150 participants will be included in this pilot study. The cohort will comprise patients who tested positive for SARS-CoV-2 infection with either an asymptomatic course or a mild course defined as no symptoms except for olfactory and taste dysfunction (n=50), patients who tested positive for SARS-CoV-2 infection with a severe disease course (n=50), and a healthy control group (n=50) with similar age and sex distribution based on frequency matching. A comprehensive neuropsychological assessment will be performed comprising nuanced aspects of complex attention, including language, executive function, verbal and visual learning, and memory. Psychiatric, personality, social and lifestyle factors, sleep, and fatigue will be evaluated. Brain magnetic resonance imaging, neurological and physical assessment, and pulmonological and lung function examinations (including body plethysmography, diffusion capacity, clinical assessments, and questionnaires) will also be performed. Three visits are planned with comprehensive testing at the baseline and 12-month visits, along with brief neurological and neuropsychological examinations at the 6-month assessment. Blood-based biomarkers of neurodegeneration will be quantified at baseline and 12-month follow-up. Results At the time of submission, the study had begun recruitment through telephone and in-person screenings. The first patient was enrolled in the study at the beginning of April 2021. Interim data analysis of baseline information is expected to be complete by December 2021 and study completion is expected at the end of December 2022. Preliminary group comparisons indicate worse word list learning, short- and long-delayed verbal recall, and verbal recognition in both patient cohorts compared with those of the healthy control group, adjusted for age and sex. Initial volumetric comparisons show smaller grey matter, frontal, and temporal brain volumes in both patient groups compared with those of healthy controls. These results are quite robust but are neither final nor placed in the needed context intended at study completion. Conclusions To the best of our knowledge, this is the first study to include objective and comprehensive longitudinal analyses of neurocognitive sequelae of COVID-19 in an extreme group comparison stratified by disease severity with healthy controls actively recruited during the pandemic. Results from this study will contribute to the nascent literature on the prolonged effects of COVID-19 on neurocognitive performance via our coassessment of neuroradiological, neurological, pulmonary, psychiatric, and lifestyle factors. Trial Registration International Clinical Trials Registry Platform DRKS00023806; https://trialsearch.who.int/Trial2.aspx?TrialID=DRKS00023806 International Registered Report Identifier (IRRID) DERR1-10.2196/30259

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Section: Discussionsupporting

confidence: 91%

Longitudinal Neurocognitive and Pulmonological Profile of Long COVID-19: Protocol for the COVIMMUNE-Clin Study

Widmann¹,

Wieberneit²,

Bieler³

et al. 2021

JMIR Res Protoc

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show abstract

“…Although considered as a respiratory disease, COVID-19 has become increasing recognized as neurotropic since patients might experience mild to severe neurological symptoms [ 2 , 3 ]. Using magnetic resonance imaging (MRI), previous studies reported that half of the COVID-19 patients have brain structural abnormalities, including white matter hyperintensities [ 4 , 5 ] and frontal-temporal gray matter volume abnormalities [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Post-traumatic stress symptoms in COVID-19 survivors: a self-report and brain imaging follow-up study

Zhang

Liu

et al. 2021

Mol Psychiatry

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Previous coronavirus pandemics were associated elevated post-traumatic stress symptoms (PTSS), but the self-report and neurological basis of PTSS in patients who survived coronavirus disease 2019 (COVID-19) are largely unknown. We conducted a two-session study to record PTSS in the COVID-19 survivors discharged from hospitals for a short (i.e., about 3 months, Session 1) to a medium period (i.e., about 6 months, Session 2), as well as brain imaging data in Session 2. The control groups were non-COVID-19 locals. Session 1 was completed for 126 COVID-19 survivors and 126 controls. Session 2 was completed for 47 COVID-19 survivors and 43 controls. The total score of post-traumatic stress disorder (PTSD) checklist for DSM-5 (PCL-5) score was significantly higher in COVID-19 survivors compared with controls in both sessions. The PCL-5 score in COVID-19 survivors was positively correlated with the duration after discharge (r = 0.27, p = 0.003 for Session 1), and increased by 20% from Session 1 to Session 2 for the survivors who participated both sessions. The increase was positively correlated with individual's test-retest duration (r = 0.46, p = 0.03). Brain structural volume and functional activity in bilateral hippocampus and amygdala were significantly larger in COVID-19 survivors compared with controls. However, the volumes of the left hippocampus and amygdala were negatively correlated with the PCL-5 score for the COVID-19 survivors. Our study suggests that COVID-19 survivors might face possible PTSS deteriorations, and highlights the importance of monitoring mental wellness of COVID-19 survivors.

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“…We report the case of a woman with long COVID and SARS-CoV-2 RNA real-time reverse transcriptase polymerase chain reaction (RT-PCR) detection in the CSF, which seems important given that at least two separate recent reports describe gray matter volume loss in various regions of the brain immediately, as well as within a few months after COVID-19. 4 , 5 Together, these two studies provide both a comparison of patients with and without recent COVID-19, (4 – this should be a supersript referring to reference number 4) and a comparison of brain scans before and after COVID-19. (5 – this should be a supersript referring to reference number 5)…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 RNA in the Cerebrospinal Fluid of a Patient with Long COVID

Viszlayová

Sojka

Dobrodenková³

et al. 2021

Therapeutic Advances in Infection

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Over 10% of COVID-19 convalescents report post-COVID-19 complications, namely, ‘long COVID’ or ‘post-COVID syndrome,’ including a number of neuro-psychiatric symptoms. The pathophysiology of COVID-19 in the central nervous system is poorly understood but may represent post-COVID injury, ongoing sterile maladaptive inflammation, or SARS-CoV-2 persistence. We describe a long COVID patient with SARS-CoV-2 RNA in the cerebrospinal fluid, which seems important, specifically due to recent reports of gray matter volume loss in COVID-19 patients. Further studies of SARS-CoV2 RNA, markers of inflammation, and neuronal damage in the CSF of patients with long COVID would be useful and should address whether the CNS can serve as a reservoir of SARS-CoV-2, clarify the pathway by which COVID-19 contributes to CNS dysfunction, and how best to therapeutically address it.

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Alterations of frontal-temporal gray matter volume associate with clinical measures of older adults with COVID-19

Cited by 53 publications

References 68 publications

Longitudinal Neurocognitive and Pulmonological Profile of Long COVID-19: Protocol for the COVIMMUNE-Clin Study

Longitudinal Neurocognitive and Pulmonological Profile of Long COVID-19: Protocol for the COVIMMUNE-Clin Study

Post-traumatic stress symptoms in COVID-19 survivors: a self-report and brain imaging follow-up study

SARS-CoV-2 RNA in the Cerebrospinal Fluid of a Patient with Long COVID

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