# Cognitive and Neuropsychiatric Sequelae After SARS-CoV-2 Infection: A Narrative Review and Exploratory Cross-Sectional Study of Neurofilament Light Chain and GFAP

## TL;DR

People recovering from moderate or severe COVID-19 often experience long-term cognitive and mental health issues, but these symptoms don't clearly link to specific brain injury markers in the blood.

## Contribution

This study explores the lack of correlation between blood biomarkers of neuronal injury and persistent neuropsychiatric symptoms in post-COVID patients.

## Key findings

- Post-COVID patients with moderate or severe infections show higher rates of cognitive and neuropsychiatric symptoms.
- Neurofilament light chain and GFAP levels in blood do not consistently correlate with symptom severity.
- Ongoing symptoms may involve mechanisms beyond neuronal or astrocytic injury.

## Abstract

What are the main findings?
Post-COVID-19 patients exhibit persistent cognitive and neuropsychiatric symptoms independent of clear biomarker correlations.Serum neurofilament light chain and GFAP levels were explored without consistent associations with neuropsychiatric symptom severity.

Post-COVID-19 patients exhibit persistent cognitive and neuropsychiatric symptoms independent of clear biomarker correlations.

Serum neurofilament light chain and GFAP levels were explored without consistent associations with neuropsychiatric symptom severity.

What are the implications of the main findings?
Persistent post-COVID neuropsychiatric symptoms may occur despite the absence of robust neuroglial biomarker alterations.Clinical assessment remains essential, while blood-based biomarkers require further validation in post-COVID populations.

Persistent post-COVID neuropsychiatric symptoms may occur despite the absence of robust neuroglial biomarker alterations.

Clinical assessment remains essential, while blood-based biomarkers require further validation in post-COVID populations.

Background: Persistent cognitive and neuropsychiatric symptoms have been increasingly reported as part of the post-COVID-19 condition. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are circulating biomarkers of neuronal and astrocytic injury that increase during acute SARS-CoV-2 infection; however, their role in long-term neuropsychiatric sequelae remains unclear. Objective: To provide a narrative overview of cognitive and neuropsychiatric sequelae following SARS-CoV-2 infection and to explore the association of plasma NfL and GFAP concentrations with cognitive impairment and neuropsychiatric symptoms in individuals recovered from COVID-19. Methods: A narrative review of the literature was conducted, followed by an exploratory cross-sectional study including 41 adults recovered from SARS-CoV-2 infection. Participants were classified according to acute disease severity into two groups. Cognitive function was assessed using MoCA, and neuropsychiatric symptoms were evaluated using DASS-21. Plasma NfL and GFAP concentrations were measured by ELISA. Group comparisons and Spearman correlation analyses were performed. Results: A total of 41 individuals were studied; they recovered from moderate or severe COVID-19 and exhibited a higher prevalence of cognitive impairment and neuropsychiatric symptoms compared with those who recovered from mild or asymptomatic infection. Plasma NfL and GFAP concentrations did not differ significantly between severity groups. NfL showed a weak association with the presence of post-COVID-19 condition. Conclusions: This study highlights the high burden of persistent cognitive and neuropsychiatric symptoms following moderate and severe SARS-CoV-2 infection. The absence of sustained elevations in circulating NfL and GFAP nearly two years after infection suggests that ongoing symptoms may involve mechanisms beyond overt neuronal or astrocytic injury.