To compare serum neuroinflammatory and brain damage biomarkers between Cognitively Impaired and Unimpaired patients at baseline, 3/6, and 12 months after COVID-19 hospitalization.

Post-acute sequelae of SARS-CoV-2 infection (PASC), also known as Long-COVID, affects millions worldwide. A subset of long-COVID survivors exhibit persistent neuropsychiatric symptoms; however, the underlying mechanisms for this outcome are unknown. Research determined that COVID-19 can cause long-term neuroinflammation. Thus, chronic neuroinflammation and its associated brain injury outcomes may lead to neuropsychiatric symptoms in Long-COVID survivors.

Participants were recruited from a well-characterized COVID-19 biorepository made up of previously cognitively unimpaired survivors who were hospitalized due to complications from acute SARS-CoV2 infection. BrainCheck, a digital biomarker tool, was used to classify the cognitive status as Impaired (≤85) and Unimpaired (>85) at 24 months post-hospitalization. Serum levels of neuroinflammatory biomarkers were measured at baseline, 3/6-, and 12-months post-hospitalization and compared between the groups by the Mann-Whitney U Test. Also, linear regression analysis was conducted to compare the group differences in neuroinflammatory biomarkers, adjusting for age, sex, and Hispanic as covariates.

The Impaired group showed significantly higher levels of Enolase at baseline (P=0.034) and IL10 at 12 months (P = 0.023) compared to the Unimpaired group. When considering the covariates, the Impaired group presented higher NFL (P=0.050) and lower IP10 levels (P=0.063) at baseline, respectively. The Impaired group also showed higher levels of IL1RA (P=0.032) at 3/6 months and
higher IL10 levels (P=0.060) at 12 months.

Understanding the neuropathology of COVID-19 infection requires knowledge of the role played by neuroinflammation, hypoxic brain injury biomarkers, and synaptic regulatory proteins. Future longitudinal studies will explore an expanded biomarker panel, metabolomic profiles, and neuroimaging in this cohort.