Cognitive Impairment in Long COVID: Molecular Mimicry and Neurofilament Light Chain (NfL) as Disease Mechanisms
Elisa Gouvea1, Renan Fernandes1, Jessica Raposo-Vedovi1, Andreza Salvio1, Larissa Duarte1, Fabricia Fontes-Dantas2, Soniza Alves-Leon1
1Translational Neuroscience Laboratory, Federal University of the State of Rio de Janeiro, 2Department of Pharmacology, Rio de Janeiro State University
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.