Cognitive Impairment and CSF Analyses After Covid-19: A Prospective Cohort Study
Flavia Dahy1, Aline Matos2, João Victor Luisi de Moura3, Thais Romano4, Rosa Marcusso3, Tatiane Assone5, Camila Romano2, Augusto César Penalva de Oliveira3, Jorge Casseb6, Jerusa Smid7
1University of São Paulo, 2Faculty of Medicine, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil., 3Institute of Infectious Diseases "Emilio Ribas", São Paulo, Brazil., 4Federal University of São Paulo, São Paulo, Brazil., 5Laboratory of Investigation in Dermatology and Immunodeficiencies, Department of Dermatology, Faculty of Medicine, Universidade de São Paulo, São Paulo, SP, Brazil, 6Department of Dermatology, Faculty of Medicine, Universidade de São Paulo, São Paulo, SP, Brazil. Laboratory of Investigation in Dermatology and Immunodeficiencies, Department of Dermatology, Faculty of Medicine, Universidade de São Paulo, São Paulo, SP, Brazil., 7Private Office
Objective:
To identify cerebrospinal fluid (CSF) SARS-CoV-2 RNA, biomarkers and pro-inflammatory cytokines associated with cognitive impairment after covid-19.
Background:
Post-covid cognitive dysfunction represents a frequent and disabling manifestation of long covid, with estimated prevalence ranging from 10% to 20% of survivors. Elevated systemic inflammatory markers such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α have been reported, but their relationship with cognitive outcomes and CSF inflammatory signatures remains unclear.
Design/Methods:
We conducted a prospective longitudinal study at a referral center for infectious diseases in Brazil between June 2020 and July 2021. Adults with neurological complaints after covid-19 underwent cognitive screening with the Addenbrooke’s Cognitive Examination–Revised and the Mini-Mental State Examination. Cognitive impairment was defined as abnormal performance in both tests. CSF samples were collected following cognitive assessment and analyzed for detection of SARS-CoV-2 RNA, glial fibrillary acidic protein (GFAP), neurofilament heavy chain (NF-H), and pro-inflammatory cytokines including interferon (IFN)-γ, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-18, and TNF-α using multiplex immunoassays.
Results:
Twenty patients were enrolled (50% male; mean age 45.4 ± 9.2 years; median 44.5 years). Cognitive impairment was identified in nine participants (45%). The mean time between covid-19 onset and CSF collection was 130.9 days (SD 100.4; median 103.5 days). No control group without covid-19 was included. We observed no differences in basic CSF analysis. Comparative analysis showed no significant differences in CSF biomarker or cytokine concentrations between patients with and without cognitive impairment. One patient without cognitive impairment had detectable SARS-CoV-2 RNA in the CSF, with no evidence of blood contamination. This CSF was collected 100 days after covid-19 was confirmed, and basic analysis of the material was normal.
Conclusions:
In this cohort of post-covid patients, cognitive impairment was frequent but not associated with classical CSF pro-inflammatory biomarkers.
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