Assessing functional connectivity differences and work-related fatigue in surviving COVID-negative patients

Hafiz, Rakibul; Gandhi, Tapan Kumar; Misrhra, Sapna; Prasad, Alok; Mahajan, Vidur; Natelson, Benjamin H.; Di, Xin; Biswal, Bharat B.

doi:10.1101/2022.02.01.478677

Cited by 10 publications

(10 citation statements)

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“…Only studies assessing subjective complaints have reported forgetfulness related to how to do routine tasks in 15% of cases (Davis et al, 2021;Callan et al, 2022), and no studies to date have assessed this memory using objective measures of performance. Magnetic resonance imaging 2 weeks after hospital discharge in COVID survivors (Hafiz et al, 2022) or long-COVID patients (Besteher et al, 2022) showed basal ganglia and limbic system alterations in comparison with controls. These brain abnormalities were associated with fatigue symptoms in the post-acute phase (Hafiz et al, 2022).…”

Section: Introductionmentioning

confidence: 94%

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Anosmia in COVID-19 could be associated with long-term deficits in the consolidation of procedural and verbal declarative memories

et al. 2022

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Background and purposeLong-COVID describes the long-term effects of the coronavirus disease 2019 (COVID-19). In long-COVID patients, neuropsychological alterations are frequently reported symptoms. Research points to medial temporal lobe dysfunction and its association with anosmia in long-COVID patients. This study aims to investigate the acquisition and consolidation of declarative and procedural memory in long-COVID patients and to explore whether anosmia is related to these dissociated memory functions.MethodsForty-two long-COVID participants and 30 controls (C) were recruited. The sample of long-COVID patients was divided into two groups based on the presence or absence of anosmia, group A and group NA, respectively. Objective performance in verbal declarative memory (Paired-Associate Learning, PAL), procedural memory (Mirror Tracing Test, MTT), general cognitive function (Montreal Cognitive Assessment scale), psychomotor speed, and incidental learning (Digit Symbol Substitution Test) were assessed and compared among the A, NA, and C groups. Long-term retention of PAL and MTT were assessed 24 h after acquisition.ResultsLower scores in general cognition, psychomotor speed, and sustained attention were found in A and NA compared with C. However, incidental learning, both cue-guided and free-recalled, was diminished in group A compared with C, with no differences with group NA. General cognition and incidental learning were related to declarative memory function exclusively in long-COVID groups. Long-COVID groups presented lower long-term retention of verbal declarative memory than controls in recall tests but no differences in recognition tests. No group differences were found in the acquisition of procedural memory. However, long-term retention of this memory was worse in group A as compared to the NA and C groups, respectively, when errors and time of execution were considered.ConclusionFindings support that consolidation of both procedural and declarative memories is more affected than the acquisition of these memories in long-COVID patients, who are also more vulnerable to deficits in delayed recall than in recognition of declarative memories. Deficits in the consolidation of procedural memory and immediate recall of declarative information are especially relevant in long-COVID participants with anosmia. This indicates that anosmia in COVID-19 could be associated with a long-term dysfunction of the limbic system.

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Section: Introductionmentioning

confidence: 94%

“…Magnetic resonance imaging 2 weeks after hospital discharge in COVID survivors (Hafiz et al, 2022) or long-COVID patients (Besteher et al, 2022) showed basal ganglia and limbic system alterations in comparison with controls. These brain abnormalities were associated with fatigue symptoms in the post-acute phase (Hafiz et al, 2022).…”

Section: Introductionmentioning

confidence: 94%

Anosmia in COVID-19 could be associated with long-term deficits in the consolidation of procedural and verbal declarative memories

et al. 2022

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“…Similar to our study, areas in the brain have been found to be related to fatigue in other reports as well. A functional connectivity analysis [50] has reported a negative correlation between fatigue and connectivity in the precuneus network which involves the left superior parietal lobule, the superior occipital gyrus, the angular gyrus, and precuneus. A volumetric study [51] on the brain of COVID affected patients has reported fatigue to be positively correlated to volume of the left posterior cingulate cortex, precuneus, and the superior parietal lobule.…”

Section: Discussionmentioning

confidence: 99%

Brain Alterations in COVID Recovered Revealed by Susceptibility-Weighted Magnetic Resonance Imaging

Mishra¹,

Hafiz

Misra³

et al. 2022

Preprint

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The increasing number of reports of mild to severe psychological, behavioral, and cognitive sequelae in COVID-19 survivors motivates a need for a thorough assessment of the neurological effects of the disease. In this regard, we have conducted a neuroimaging study to understand the neurotropic behavior of the coronavirus. We hypothesize that the COVID-recovered subjects have developed alterations in the brain which can be measured through susceptibility differences in various regions of the brain when compared to healthy controls (HCs). Hence, we performed our investigations on susceptibility-weighted imaging (SWI) volumes. Fatigue, being of the most common symptoms of Long COVID, has also been studied in this work. SWI volumes of 46 COVID and 30 HCs were included in this study. The COVID patients were imaged within six months of their recovery. We performed an unpaired two-sample t-test over the pre-processed SWI volumes of both groups and multiple linear regression was performed to observe group differences and correlation of fatigue with SWI values. The group analysis showed that COVID recovered subjects had significantly higher susceptibility imaging values in regions of the frontal lobe and the brain stem. The clusters obtained in the frontal lobe primarily show differences in the white matter regions. The COVID group also demonstrated significantly higher fatigue levels than the HC group. The regression analysis on the COVID group yielded clusters in the anterior cingulate gyrus and midbrain, which exhibited negative correlations with fatigue scores. This study suggests an association of Long COVID with prolonged effects on the brain and also indicates the viability of the SWI modality for analysis of post-COVID symptoms.

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“…We hypothesized that the adults who previously self-isolated due to COVID-19 would exhibit altered CBF relative to controls, when assessed weeks/months beyond infection. Given the prevalence of fatigue as a symptom of the post-COVID-19 condition, 7,8,[32][33][34][35] we then performed an exploratory analysis of the association between self-reported fatigue and CBF among COVID-19 participants.…”

Section: Introductionmentioning

confidence: 99%

“…32,33 Others have observed fatigue-related differences in brain structure and function in those recovering from COVID-19, 35 such as functional connectivity alterations in parietal regions. 34 Interestingly, the post-COVID-19 condition shares many common features with chronic fatigue syndrome (i.e., myalgic encephalomyelitis), a disorder that can be triggered by viral infection, 63 and that is characterized by decreased CBF, such as within the lingual gyrus. 64,65 Therefore, these fatigue-related CBF differences amongst COVID-19 participants could help guide therapeutic efforts in treating fatigue as a symptom of the post-COVID-19 condition.…”

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confidence: 99%

Decreased cerebral blood flow in non-hospitalized adults who self-isolated due to COVID-19

Kim

Roudaia

et al. 2022

Preprint

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The long-term consequences of coronavirus disease 2019 (COVID-19) on brain physiology and function are not yet well understood. From the recently described NeuroCOVID-19 study, we examined cerebral blood flow (CBF) in 50 participants recruited to one of two groups: 1) adults who previously self-isolated at home due to COVID-19 (n = 39; 116.5 ± 62.2 days since positive diagnosis), or 2) controls who experienced flu-like symptoms but had a negative COVID-19 diagnosis (n = 11). Participants underwent arterial spin labeling magnetic resonance imaging at 3 T to yield measures of CBF. Voxel-wise analyses of CBF were performed to assess for between-group differences, after controlling for age and sex. Relative to controls, the COVID-19 group exhibited decreased CBF in the thalamus, orbitofrontal cortex, and regions of the basal ganglia. Within the COVID-19 group, CBF differences in occipital and parietal regions were observed between those with (n = 11) and without (n = 28) self-reported on-going fatigue. These results suggest long-term changes in brain physiology in adults across the post-COVID-19 timeframe. Moreover, CBF may aid in understanding the heterogeneous symptoms of the post-COVID-19 condition. Future longitudinal studies are needed to further characterize the consequences of COVID-19 on the brain.

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Assessing functional connectivity differences and work-related fatigue in surviving COVID-negative patients

Cited by 10 publications

References 95 publications

Anosmia in COVID-19 could be associated with long-term deficits in the consolidation of procedural and verbal declarative memories

Anosmia in COVID-19 could be associated with long-term deficits in the consolidation of procedural and verbal declarative memories

Brain Alterations in COVID Recovered Revealed by Susceptibility-Weighted Magnetic Resonance Imaging

Decreased cerebral blood flow in non-hospitalized adults who self-isolated due to COVID-19

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