Host Genetic Variants Linked to COVID-19 Neurological Complications and Susceptibility in Young Adults—A Preliminary Analysis

To date, multiple efforts have been made to use genome-wide association studies (GWAS) to untangle the genetic basis for SARS-CoV-2 infection susceptibility and severe COVID-19. However, data on the genetic-related effects of SARS-CoV-2 infection on the presence of accompanying and long-term post-COVID-19 neurological symptoms in younger individuals remain absent. We aimed to examine the possible association between SNPs found in a GWAS of COVID-19 outcomes and three phenotypes: SARS-CoV-2 infection, neurological complications during disease progression, and long-term neurological complications in young adults with a mild-to-moderate disease course. University students (N = 336, age 18–25 years, European ancestry) with or without COVID-19 and neurological symptoms in anamnesis comprised the study sample. Logistic regression was performed with COVID-19-related phenotypes as outcomes, and the top 25 SNPs from GWAS meta-analyses and an MR study linking COVID-19 and cognitive deficits were found. We replicated previously reported associations of the FURIN and SLC6A20 gene variants (OR = 2.36, 95% CI 1.31–4.24) and OR = 1.94, 95% CI 1.08–3.49, respectively) and remaining neurological complications (OR = 2.12, 95% CI 1.10–4.35 for SLC6A20), while NR1H2 (OR = 2.99, 95% CI 1.39–6.69) and TMPRSS2 (OR = 2.03, 95% CI 1.19–3.50) SNPs were associated with neurological symptoms accompanying COVID-19. Our findings indicate that genetic variants related to a severe COVID-19 course in adults may contribute to the occurrence of neurological repercussions in individuals at a young age.

[1]  Nguyen Hai Ha,et al.  Host Genetic Risk Factors Associated with COVID-19 Susceptibility and Severity in Vietnamese , 2022, Genes.

[2]  S. Jerônimo,et al.  Genome-wide association studies of COVID-19: Connecting the dots , 2022, Infection, Genetics and Evolution.

[3]  J. Zawilska,et al.  Psychiatric and neurological complications of long COVID , 2022, Journal of Psychiatric Research.

[4]  W. Brola,et al.  Neurological consequences of COVID-19 , 2022, Pharmacological Reports.

[5]  A. Kazantseva,et al.  Role Of Retroelements In The Development Of COVID-19 Neurological Consequences , 2022, Russian Open Medical Journal.

[6]  A. Baranova,et al.  Causal effect of COVID‐19 on Alzheimer's disease: A Mendelian randomization study , 2022, Journal of medical virology.

[7]  Joseph T. Glessner,et al.  COVID-19 in pediatrics: Genetic susceptibility , 2022, Frontiers in Genetics.

[8]  Partha Pakray,et al.  An improved Fuzzy based GWO algorithm for predicting the potential host receptor of COVID-19 infection , 2022, Computers in Biology and Medicine.

[9]  John M. Santoro,et al.  Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis , 2022, PloS one.

[10]  S. Furini,et al.  Host genetic basis of COVID-19: from methodologies to genes , 2022, European Journal of Human Genetics.

[11]  Rossana Botto,et al.  Anxiety and depression in Alzheimer’s disease: a systematic review of pathogenetic mechanisms and relation to cognitive decline , 2022, Neurological Sciences.

[12]  S. Lo Caputo,et al.  Neuropsychiatric Disorders in Pediatric Long COVID-19: A Case Series , 2022, Brain sciences.

[13]  Benjamin A. Logsdon,et al.  Manifestations of Alzheimer’s disease genetic risk in the blood are evident in a multiomic analysis in healthy adults aged 18 to 90 , 2022, Scientific Reports.

[14]  S. D. de Souza,et al.  The Genomic Profile Associated with Risk of Severe Forms of COVID-19 in Amazonian Native American Populations , 2022, Journal of personalized medicine.

[15]  V. Álvarez,et al.  FURIN gene variants (rs6224/rs4702) as potential markers of death and cardiovascular traits in severe COVID‐19 , 2022, Journal of medical virology.

[16]  V. Baranov,et al.  Identification of Genetic Risk Factors of Severe COVID-19 Using Extensive Phenotypic Data: A Proof-of-Concept Study in a Cohort of Russian Patients , 2022, Genes.

[17]  T. del Ser,et al.  Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study , 2021, Journal of personalized medicine.

[18]  Z. Takhirova,et al.  The role of the KIBRA and APOE genes in developing spatial abilities in humans , 2021, Vavilovskii zhurnal genetiki i selektsii.

[19]  R. Cron,et al.  Host genetics of pediatric SARS-CoV-2 COVID-19 and multisystem inflammatory syndrome in children , 2021, Current opinion in pediatrics.

[20]  Mattia G. Bergomi,et al.  Mapping the human genetic architecture of COVID-19 , 2021, Nature.

[21]  F. Mattioli,et al.  Neurological and cognitive sequelae of Covid-19: a four month follow-up , 2021, Journal of Neurology.

[22]  J. Sejvar,et al.  Prognostic Indicators and Outcomes of Hospitalised COVID-19 Patients with Neurological Disease: A Systematic Review and Individual Patient Data Meta-Analysis , 2021, SSRN Electronic Journal.

[23]  T. del Ser,et al.  Residence, Clinical Features, and Genetic Risk Factors Associated with Symptoms of COVID-19 in a Cohort of Older People in Madrid , 2021, Gerontology.

[24]  S. Semiz SIT1 transporter as a potential novel target in treatment of COVID-19 , 2021, Biomolecular concepts.

[25]  A. Menini,et al.  Six-month psychophysical evaluation of olfactory dysfunction in patients with COVID-19 , 2021, Chemical senses.

[26]  Eurie L. Hong,et al.  AncestryDNA COVID-19 Host Genetic Study Identifies Three Novel Loci , 2020, medRxiv.

[27]  Barbara B. Shih,et al.  Genetic mechanisms of critical illness in COVID-19 , 2020, Nature.

[28]  J. Porta‐Etessam,et al.  ACE2, TMPRSS2, and Furin variants and SARS‐CoV‐2 infection in Madrid, Spain , 2020, Journal of medical virology.

[29]  K. Bhaskaran,et al.  OpenSAFELY: factors associated with COVID-19 death in 17 million patients , 2020, Nature.

[30]  J. Erdmann,et al.  Genomewide Association Study of Severe Covid-19 with Respiratory Failure , 2020, The New England journal of medicine.

[31]  K. Drak Alsibai Expression of angiotensin-converting enzyme 2 and proteases in COVID-19 patients: A potential role of cellular FURIN in the pathogenesis of SARS-CoV-2 , 2020, Medical Hypotheses.

[32]  G. Poland,et al.  Does apolipoprotein E genotype predict COVID-19 severity? , 2020, QJM : monthly journal of the Association of Physicians.

[33]  Koichi Yuki,et al.  COVID-19 pathophysiology: A review , 2020, Clinical Immunology.

[34]  S. Matalon,et al.  Elevated Plasmin(ogen) as a Common Risk Factor for COVID-19 Susceptibility , 2020, Physiological reviews.

[35]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[36]  J. Hardy,et al.  Genetic variability at the LXR gene (NR1H2) may contribute to the risk of Alzheimer's disease , 2006, Neurobiology of Aging.