Cognitive and Psychological Symptoms in Post-COVID-19 Condition: A Systematic Review of Structural and Functional Neuroimaging, Neurophysiology, and Intervention Studies

Eva Pettemeridou*, Maria Loizidou, Jelena Trajkovic, Maria Constantinou, Stefanie De Smet, Chris Baeken, Alexander T. Sack, Steven C.R. Williams, Fofi Constantinidou

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Objective: To investigate the structural, functional, and neurophysiological brain changes associated with post-COVID-19 condition (PCC)-related cognitive and psychological issues and evaluate the efficacy of noninvasive brain stimulation (NIBS) and cognitive rehabilitation interventions. Data Sources: Electronic databases, including Web of Science, PubMed, and Embase, were systematically searched for articles published before February 1, 2025, using terms such as “post-COVID-19 condition,” “cognitive dysfunction,” “brain changes,” “noninvasive brain stimulation,” and “cognitive rehabilitation.” Language was restricted to English, and only studies involving human participants were included. Study Selection: Studies with human participants aged ≥18 years diagnosed with PCC, employing magnetic resonance imaging, functional magnetic resonance imaging, positron emission tomography, and electroencephalography, and interventions such as NIBS and cognitive rehabilitation were included. Articles were selected through independent review by multiple authors, with consensus resolving discrepancies. Of the 123 studies initially identified, 78 met the inclusion criteria. Data Extraction: Data on participant demographics, methodologies, neurophysiological changes, and intervention outcomes were extracted by 2 independent reviewers using predefined guidelines. Study quality was assessed using the Newcastle-Ottawa Scale and Critical Appraisal Skills Program tools. Data Synthesis: Seventy-eight studies with over 5900 participants met the inclusion criteria. Significant cognitive impairments were observed in attention, executive function, and memory (N=78). Key findings included mixed evidence of gray matter (N=16) and white matter volume changes (N=20), cortical thickness alterations (N=9), variations in functional connectivity (N=14), electrophysiology (N=9), and blood flow (N=8). NIBS, including transcranial magnetic stimulation (N=8) and transcranial direct current stimulation (N=2), showed potential benefits for managing depression and cognitive impairments. Although cognitive rehabilitation (N=3) showed promise, it requires further investigation. Conclusions: This review highlights the complex neurologic underpinnings of PCC and the potential of NIBS and cognitive rehabilitation as interventions. Further research is essential to refine these interventions and establish evidence-based strategies for addressing long-term cognitive and psychological effects of PCC.

Original languageEnglish
Article number100461
JournalArchives of Rehabilitation Research and Clinical Translation
DOIs
Publication statusAccepted/In press - 2025

Keywords

  • Brain injuries
  • Cognitive rehabilitation
  • EEG
  • Functional connectivity
  • Long COVID
  • MRI
  • Neuropsychological impairment
  • Noninvasive brain stimulation
  • Rehabilitation
  • White matter changes

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