Evaluation of neuronal and immunological biomarkers in post-COVID-19 condition

To investigate evidence of central nervous system (CNS) injury in Post-COVID-19 Condition (PCC) through plasma biomarkers of neuronal damage (APP, NfL, Tau), inflammation (IL-2, IL-6, IL-10, IL-18, IFN-γ, TNF-α), and immune response (IgM, IgA, IgG) in individuals with PCC and neurological symptoms.

We analyzed 155 volunteers from a post-COVID-19 Center in Rio de Janeiro, categorized into four groups: COVID-19 control (COV; recovered without PCC), PCC without memory loss and reasoning difficulty (PCC-noML/RD), PCC with memory loss and reasoning difficulty (PCC-ML/RD), and healthy controls (HC). Serological and biomarker analyses were used to quantify inflammatory markers, immunoglobulins, and neuronal injury-related proteins.

PCC groups showed significantly altered IgA and IgG levels compared to the COV group. Volunteers with PCC exhibited elevated IL-6, IL-18, IFN-γ, and TNF-α, alongside decreased IL-2, relative to COV and HC groups. Total Tau (t-Tau) concentrations were highest in the COV group and lowest in the PCC-noML/RD group, with the PCC-ML/RD group presenting a distinct intermediate profile. Aβ1-40 levels differed between PCC-noML/RD and PCC-ML/RD groups. A positive correlation between TNF-α and t-Tau was observed specifically in the PCC-ML/RD group.

In conclusion, our findings suggest that Post-COVID-19 Condition is associated with persistent systemic inflammation and subtle alterations in neurological biomarkers. This inflammatory profile may contribute to cognitive symptoms, including memory impairment, reasoning difficulties, and hypoprosexia, even in the absence of marked evidence of neuronal injury.