Abstract Details

Title Deciphering Genetic Modulators of Long COVID Cognitive Impairment (LCCI)

Topic Infectious Disease

Presentation(s) P1 - Poster Session 1 (11:45 AM-12:45 PM)

Poster/Presentation
Number 10-007

Objective To pinpoint genetic variations influencing Long COVID Cognitive
Impairment (LCCI).

Background LCCI is a frequent and poorly understood consequence of
COVID-19, imposing a growing burden on society.

Design/Methods We employed next-generation sequencing to analyze a
pre-selected 400-variant panel associated with neuroinflammation and related
pathways. We analyzed 49 LCCI cases and 57 post-COVID controls without
cognitive impairment. Fisher's exact test, Benjamini-Hochberg and Bonferroni
methods (p<0.05), and in-silico functional evaluation were performed.

Results LCCI patients exhibited significantly higher frequency of rs40030
(G/A>G) variant in the S-Phase Kinase-Associated Protein 2 (SKP2) gene
(p=0.006), while controls exhibited significantly higher frequency of the
alternative genotype (A/A>G) for the same variant (p=0.036). The region where
the variant is located corresponds to regions associated with the cognitive areas
of the brain. One proposed mechanism of LCCI is SARS-CoV-2 inhibits
autophagy, leading to dysregulated cellular metabolism and excessive
inflammatory and autoimmune responses. Interestingly, SKP2 is an inhibitor of
autophagy. In-silico analysis showed the G/A variant amplifies the expression of
SKP2 in the brain, while the A/A variant does the opposite. Thus, SKP2 may
play a vital role in LCCI. rs3212227 (T/G>T) of IL-12B presented higher
frequency in LCCI cases (p=0.011). IL-12B is widely related to
neurodegenerative disorders such as Alzheimer's disease (AD). This genotype
is known to amplify IL-12B expression and was significantly related to AD risk.
Finally, LCCI patients exhibited a significantly higher frequency of rs35362851
(T/G>T) in the Retinoid X Receptor Alpha (RXRA) gene. This genomic region
corresponds to an enhancer in frontal cortex, cingulate gyrus and hippocampus.
Several variants in RXRA are associated with general cognitive ability and AD
risk.

Conclusions This investigation revealed distinct genetic variants influencing
LCCI and warrants further investigation to elucidate their precise roles in this
disease. This knowledge could guide the development of personalized
prognostic tools and potentially therapeutic strategies.

Authors/Disclosures
Elisa G. Gouvea PRESENTER	Miss Gouvea has nothing to disclose.
Elielson Veloso da Silva, PhD	Dr. Veloso da Silva has nothing to disclose.
Andreza S. Lemos, PhD (UNIRIO - University of State of Rio de Janeiro)	Dr. Lemos has nothing to disclose.
Renan A. Fernandes (Universidade Federal do Estado do Rio de Janeiro)	Ms. Fernandes has nothing to disclose.
Jéssica Vedovi	Jéssica Vedovi has nothing to disclose.
Larissa Duarte (UFRJ)	Miss Duarte has nothing to disclose.
Helena França F. Ferreira, Master	Mr. Ferreira has nothing to disclose.
Soniza Vieira A. Leon, Sr., MD, PhD (Universidade Federal do Rio de Janeiro)	Dr. Leon has nothing to disclose.

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