Abstract Details

Title Cognitive Impairment in Long COVID: Molecular Mimicry and Neurofilament Light Chain (NfL) as Disease Mechanisms

Topic Infectious Disease

Presentation(s) P11 - Poster Session 11 (5:30 PM-6:30 PM)

Poster/Presentation
Number 13-001

Objective

To investigate molecular mimicry (MM) between severe acute respiratory coronavirus type 2 (SARS-CoV-2) antigens and human autoantigens related to cognitive impairment in long COVID and the relationship between plasma levels of neurofilament light chain (pNfL) in patients with long COVID and neurocognitive symptoms.

Background Neurocognitive dysfunction is one of the main long COVID symptoms. The self-antigens NMDAR1, MPO and GAD65 have been related to the neurocognitive symptoms of long COVID, and MM among SARS-CoV-2 antigens and these self-antigens may trigger autoimmunity. Additionally, pNfL is a biomarker of early involvement of the CNS in several neurological disorders and its alteration may indicate ongoing CNS disturbances as key for long COVID neurocognitive symptoms.

Design/Methods The virus antigens (Membrane, Nucleocapsid, Spike, Nsp1, Nsp2, Nsp3 and Nsp13) and human autoantigens (NMDAR1, MPO and GAD65) sequences were analyzed for linear and three-dimensional similarities, and the virus sequences were analyzed for antigenic properties. The sequences with significant similarities and antigenic properties were assessed for their binding capacity to HLA subtypes. Simultaneously, group of 63 long COVID patients with mild acute disease were divided in different groups, according to neurocognitive assessment. Plasma samples were collected during the assessment and used for measurement of pNfL with the Single molecule array (SIMOA) assays.

Results Eight arrangements had significant linear and three-dimensional overlap. All sequences presented at least one epitope with binding capacity to the chosen HLA subtypes. Levels of pNfL were significantly higher in long COVID patients with cognitive impairment then long COVID patients without (p = 0.0263). Lower cognitive scores correlated significantly with higher pNfL levels (p = 0.0219).

Conclusions Our findings demonstrate that MM between CNS autoantibodies and SARS-CoV-2 antigens, as well as higher pNfL levels in patients with cognitive impairment, may be prominent assets to understanding the pathogenesis of long COVID cognitive symptoms, even in patients with mild acute disease.

Authors/Disclosures
Elisa G. Gouvea PRESENTER	Miss Gouvea has nothing to disclose.
Renan Fernandes	No disclosure on file
Jéssica Vedovi	Jéssica Vedovi has nothing to disclose.
Andreza S. Lemos, PhD (UNIRIO - University of State of Rio de Janeiro)	Dr. Lemos has nothing to disclose.
Larissa Duarte (UFRJ)	No disclosure on file
Fabricia Fontes-Dantas	No disclosure on file
Soniza Vieira A. Leon, Sr., MD, PhD (Universidade Federal do Rio de Janeiro)	Dr. Leon has nothing to disclose.

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