Abstract
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Objectives: Given the rapid spread of SARS-CoV-2 and emerging evidence of neurological symptoms particularly in hospitalized COVID-19 patients, we prospectively examined the impact of COVID‑19 on the CNS in inpatients at the subacute and the chronic stage by FDG PET and neurological examination.
Methods: We assessed neurological and neuropsychological symptoms (Montreal Cognitive Assessment, MoCA, adjusted for years of education) and FDG PET scans in 15 COVID-19 inpatients with at least one new neurological symptom at the subacute stage (once were no longer infectious). All scans were visually read using a 3-step rating scale (normal, mildly and severely abnormal). Principal components analysis (PCA; avoiding the need of a currently unknown reference region) was employed to explore whether a spatial covariance pattern exists in COVID-19 (compared to 45 control patients without somatic CNS disease). In eight of these patients, we re-assessed FDG PET and MoCA performance at the chronic stage approximately six months after symptom onset to examine the time course of post-COVID-19 cognitive impairment. For further validation, we also conducted a conventional group analysis using statistical parametric mapping (SPM) and a white matter as reference region (given the obvious involvement of grey matter in visual analysis).
Results: 29 of 41 screened inpatients showed one or more new neurological symptoms and gave written informed consent. Initial hospitalization was done because of medical, not neurological complications; only 2 patients underwent ICU treatment. 18 of 26 (69%, 3 refused) patients showed cognitive impairment defined as MoCA≤26. 15 patients also agreed to undergo FDG PET. Visual reads indicated pathological results (mainly frontoparietal hypometabolism) in 10/15 patients at the subacute stage. We detected a highly significant (p<0.001) COVID-19-related spatial covariance pattern characterized by positive weights in brain stem, cerebellum, white matter and mesiotemporal structures and negative weights in wide-spread neocortical areas (with frontoparietal predominance). Visual reads correlated significantly with the individual pattern expression score (PES) of the COVID‑19‑related pattern (r=0.80, p<0.001) and we found a highly significant linear relationship between MoCA and the PES at the subacute stage (R2=0.62, p<0.001). Conventional SPM analysis also showed wide-spread, frontoparietal dominant neocortical hypometabolism whereas there were no hypermetabolic clusters (false discovery rate [FDR]‑corrected p<0.01). In the eight COVID-19 patients presented for a follow-up, the mean PES at the chronic stage was significantly lower compared to the subacute stage (two-tailed paired t test, p=0.002), but still at trend-level higher in comparison to the control group (one-tailed two-sample t test, p=0.06). In parallel, MoCA significantly improved from 19.1±4.5 at the subacute stage to 23.4±3.6 at the chronic stage (p<0.05), which was however still below normal in 5/8 patients. Group analysis using SPM also showed a wide-spread increase of normalized FDG uptake in frontoparietal and, to a lesser extent, temporal neocortical regions at the chronic stage compared to the subacute stage (FDR‑corrected p<0.01). At an exploratory statistical threshold (p<0.005), there was also a remaining neocortical hypometabolism in COVID-19 patients at the chronic stage compared to the control group.
Conclusions: Neocortical dysfunction accompanied by cognitive impairment was detected in two-thirds of inpatients with subacute COVID-19. Although a significant recovery of regional neuronal function and cognition can be clearly stated, residuals are still measurable in some patients six month after manifestation of COVID-19. In consequence, post-COVID-19 patients with persistent cognitive complaints should be presented to a neurologist and possibly allocated to cognitive rehabilitation programs.
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