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<p>Long COVID has been associated with persistent neurological symptoms that impair cognitive function and quality of life, raising questions about the role of genetic factors in symptom severity and persistence. Apolipoprotein E (<i>APOE</i>) polymorphisms, known for their relevance in neurodegenerative diseases, may significantly influence neurological outcomes in long COVID patients. This study aimed to investigate the relationship between <i>APOE</i> polymorphisms, specifically single nucleotide polymorphisms (SNPs) rs7412 and rs429358, and neurological and cognitive symptoms in long-term COVID patients. <i>APOE</i> genotypes were identified through the analysis of SNPs rs7412 and rs429358. Cognitive and behavioral assessments were conducted using the Mini-Mental State Examination (MMSE), the Pfeffer Functional Activities Questionnaire, the Beck Inventory for mood assessment and the Epworth Sleepiness Scale (ESS). Statistical analyses included Mann–Whitney <i>U</i> test, chi-square or Fisher’s exact test, and odds ratio calculation, using R Studio and GraphPad Prism. The results indicated that the ε2ε3 genotype was associated with lower scores on the BECK, suggesting fewer depressive symptoms, while the ε3ε3 genotype was linked to an increase in depressive symptoms. Furthermore, analyses of <i>APOE</i> alleles showed an opposite pattern concerning daytime sleepiness: carriers of the ε2 allele exhibited greater daytime sleepiness, whereas ε3 allele carriers reported less sleepiness, as measured by the ESS. The analysis of the rs7412 SNP revealed significant impacts on both BECK and ESS scores. These findings suggest that <i>APOE</i> polymorphisms, particularly the ε2 and ε3 alleles, play a crucial role in modulating neurological and cognitive symptoms associated with long COVID. The results highlight the potential of genetic screening to identify patients at higher risk of persistent cognitive and emotional alterations, emphasizing the importance of personalized management strategies and the need for further research in diverse populations.</p>

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Associations Between APOE Polymorphisms, Neurological Symptoms, and Cognitive Assessments in Long COVID Patients: An Analysis of SNPs rs7412 and rs429358

  • 期刊论文

  • 发表日期：

    2025年11月21日

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  • Isadora de Almeida Gomes,
  • Pedro Braga-Neto,
  • Thiago Loreto Matos,
  • Emerson Lucena da Silva,
  • Lais Lacerda Brasil de Oliveira,
  • Luina Benevides Lima,
  • José Wagner Leonel Tavares-Júnior,
  • Alissa Elen Formiga Moura,
  • Marcello Holanda de Andrade,
  • Thaís de Maria Frota Vasconcelos,
  • Reinaldo Barreto Oriá,
  • Danilo Nunes Oliveira,
  • Manoel Alves Sobreira-Neto,
  • Pedro Filho Noronha Souza,
  • Maria Elisabete Amaral de Moraes,
  • Felipe Pantoja Mesquita,
  • Raquel Carvalho Montenegro

摘要

Long COVID has been associated with persistent neurological symptoms that impair cognitive function and quality of life, raising questions about the role of genetic factors in symptom severity and persistence. Apolipoprotein E (APOE) polymorphisms, known for their relevance in neurodegenerative diseases, may significantly influence neurological outcomes in long COVID patients. This study aimed to investigate the relationship between APOE polymorphisms, specifically single nucleotide polymorphisms (SNPs) rs7412 and rs429358, and neurological and cognitive symptoms in long-term COVID patients. APOE genotypes were identified through the analysis of SNPs rs7412 and rs429358. Cognitive and behavioral assessments were conducted using the Mini-Mental State Examination (MMSE), the Pfeffer Functional Activities Questionnaire, the Beck Inventory for mood assessment and the Epworth Sleepiness Scale (ESS). Statistical analyses included Mann–Whitney U test, chi-square or Fisher’s exact test, and odds ratio calculation, using R Studio and GraphPad Prism. The results indicated that the ε2ε3 genotype was associated with lower scores on the BECK, suggesting fewer depressive symptoms, while the ε3ε3 genotype was linked to an increase in depressive symptoms. Furthermore, analyses of APOE alleles showed an opposite pattern concerning daytime sleepiness: carriers of the ε2 allele exhibited greater daytime sleepiness, whereas ε3 allele carriers reported less sleepiness, as measured by the ESS. The analysis of the rs7412 SNP revealed significant impacts on both BECK and ESS scores. These findings suggest that APOE polymorphisms, particularly the ε2 and ε3 alleles, play a crucial role in modulating neurological and cognitive symptoms associated with long COVID. The results highlight the potential of genetic screening to identify patients at higher risk of persistent cognitive and emotional alterations, emphasizing the importance of personalized management strategies and the need for further research in diverse populations.