Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19

Abstract

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, neurological symptoms increasingly moved into the focus of interest. In this prospective cohort study, we assessed neurological and cognitive symptoms in hospitalized coronavirus disease-19 (COVID-19) patients and aimed to determine their neuronal correlates. Patients with reverse transcription-PCR-confirmed COVID-19 infection who required inpatient treatment primarily because of non-neurological complications were screened between 20 April 2020 and 12 May 2020. Patients (age > 18 years) were included in our cohort when presenting with at least one new neurological symptom (defined as impaired gustation and/or olfaction, performance < 26 points on a Montreal Cognitive Assessment and/or pathological findings on clinical neurological examination). Patients with ≥2 new symptoms were eligible for further diagnostics using comprehensive neuropsychological tests, cerebral MRI and 18fluorodeoxyglucose (FDG) PET as soon as infectivity was no longer present. Exclusion criteria were: premorbid diagnosis of cognitive impairment, neurodegenerative diseases or intensive care unit treatment. Of 41 COVID-19 inpatients screened, 29 patients (65.2 ± 14.4 years; 38% female) in the subacute stage of disease were included in the register. Most frequently, gustation and olfaction were disturbed in 29/29 and 25/29 patients, respectively. Montreal Cognitive Assessment performance was impaired in 18/26 patients (mean score 21.8/30) with emphasis on frontoparietal cognitive functions. This was confirmed by detailed neuropsychological testing in 15 patients. 18FDG PET revealed pathological results in 10/15 patients with predominant frontoparietal hypometabolism. This pattern was confirmed by comparison with a control sample using voxel-wise principal components analysis, which showed a high correlation (R2 = 0.62) with the Montreal Cognitive Assessment performance. Post-mortem examination of one patient revealed white matter microglia activation but no signs of neuroinflammation. Neocortical dysfunction accompanied by cognitive decline was detected in a relevant fraction of patients with subacute COVID-19 initially requiring inpatient treatment. This is of major rehabilitative and socioeconomic relevance.

NOX2 Activation in COVID-19: Possible Implications for Neurodegenerative Diseases

“…Hence, the disruption of the SP33-IRF9 axis promoted by SARS CoV-2 infection would activate the inflammatory phenotype of microglia which over time can induce neurodegeneration [41]. This evidence was found in a patient with COVID-19 in whom a strong microglial activation was found within the white matter [42]. This information supports the hypothesis that SARS CoV-2 infection may induce severe neurological repercussions related to its invasion in the nervous system [29].…”

Rapid vigilance and episodic memory decrements in COVID-19 survivors

“…Particular impairments were found in attention [6][7][8][9][10][11][12] , memory [6][7][8][10][11][12][13] and executive functions. [10][11][12][14][15][16] More recently, using 18 F-FDG PET, it has been demonstrated that in the most severely affected patients, the degree of cognitive impairment was accompanied by frontoparietal hypometabolism. 10,11 Understandably, most of these small-scale reports have, to date, predominantly focused on symptomatic, hospitalised patients (however see 17 ).…”

“…[10][11][12][14][15][16] More recently, using 18 F-FDG PET, it has been demonstrated that in the most severely affected patients, the degree of cognitive impairment was accompanied by frontoparietal hypometabolism. 10,11 Understandably, most of these small-scale reports have, to date, predominantly focused on symptomatic, hospitalised patients (however see 17 ). But what about individuals who have not been hospitalised and do not report any ongoing symptoms after recovery?…”

Neurologische Manifestationen bei Patienten mit Post-COVID-19-Syndrom

“…Am Beispiel der Fatigue werden neurotransmittervermittelte Veränderungen, eine postinfektiös fortbestehende Entzündung sowie (virusgetriggerte) immunvermittelte Mechanismen diskutiert [ 13 ]. Mittels der 18 FDG-PET (Fluordesoxyglukosepositronenemissionstomographie mit [ 18 F]) wurde bei 10 von 15 Long-COVID-Patienten mit neurokognitivem Defizit (weniger als 26/30 Punkte im MoCA[„Montreal cognitive assessment“]-Test) in frontoparietalen Hirnregionen ein Hypometabolismus nachgewiesen [ 5 ]. Beim Follow-up [ 2 ] von 8 Patienten über 6 Monate zeigte sich eine Symptomverbesserung mit weitgehender Normalisierung des Hirnstoffwechsels in der PET.…”