Systemic inflammation relates to neuroaxonal damage associated with long-term cognitive dysfunction in COVID-19...

Area of Science:

• Neurology
• Immunology
• Critical Care Medicine

Background:

• Cognitive deficits are a recognized long-term consequence of severe COVID-19.
• The mechanisms linking severe COVID-19 to neurological sequelae, particularly cognitive impairment, are not fully understood.
• Systemic inflammation's role in brain effects following severe COVID-19 requires further investigation.

Purpose of the Study:

• To investigate the relationship between systemic inflammation, neuroaxonal damage, and long-term cognitive impairment in severe COVID-19 survivors.
• To analyze the trajectories of systemic inflammation and neuroaxonal damage biomarkers during ICU admission.
• To determine if blood biomarker levels during intensive care unit (ICU) stay can predict cognitive outcomes post-discharge.

Main Methods:

• A prospective longitudinal cohort study involving patients who survived severe COVID-19 and ICU admission.
• Consecutive blood sampling during ICU stay to measure inflammatory cytokines and neurofilament light chain (NfL) using Luminex and Simoa.
• Comprehensive neuropsychological assessment conducted six months after ICU discharge to evaluate cognitive function.

Main Results:

• Plasma NfL concentrations significantly increased during ICU stay in 95% of patients (from 23 to 250 pg/mL).
• Systemic inflammation markers at day 14 predicted NfL levels at day 14 (R² = 44%), indicating a link between inflammation and neuroaxonal damage.
• Twenty-seven percent of patients showed cognitive impairment six months post-ICU discharge, with higher NfL levels correlating with poorer cognitive outcomes, especially in processing speed.

Conclusions:

• Sustained systemic inflammation in critically ill COVID-19 patients is associated with neuroaxonal damage and subsequent long-term cognitive impairment.
• Plasma NfL levels measured during ICU stay may serve as a prognostic biomarker for predicting long-term cognitive impairment in severe COVID-19 survivors.
• Understanding the inflammation-brain axis is crucial for managing neurological sequelae after severe COVID-19.