The literature reports several symptoms of SARS-CoV-2 in humans such as fever, cough, fatigue, pneumonia, and headache. Furthermore, patients infected with similar strains (SARS-CoV and MERS-CoV) suffered testis, liver, or thyroid damage.Angiotensin-converting enzyme 2 (ACE2) serves as an entry point into cells for some strains of coronavirus (SARS-CoV, MERS-CoV, SARS-CoV-2). Our hypothesis was that as ACE2 is essential to the SARS-CoV-2 virus invasion, then brain regions where ACE2 is the most expressed are more likely to be disturbed by the infection.Thus, the expression of other genes which are also over-expressed in those damaged areas could be affected. We used mRNA expression levels data of genes provided by the Allen Human Brain Atlas (ABA), and computed spatial correlations with the LinkRbrain platform. Genes whose co-expression is spatially correlated to that of ACE2 were then clustered into 16 groups, depending on the organ in which they are the most expressed (as described by the NCBI genes database). The list of organs where genes sharing local over-expression with the ACE2 gene are the most expressed is astonishingly similar to the organs affected by
As the COVID-19 pandemic continues to unfold, numerous neurological symptoms emerge. The literature reports more and more manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) related to headache, dizziness, impaired consciousness, cognitive impairment, and motor disorders. Moreover, the infection of SARS-CoV-2 may have a durable neurological impact. ACE2/TMPRSS2 is the main entry point into cells for some strains of coronaviruses (CoVs), including SARS-CoV-2, which uses it to target the central nervous system (CNS). The aim of this study was to characterize the scope of the potential complex impact of a SARS-CoV-2 infection in the brain. It concerns different scales: the topographic, cognitive, sensorimotor, and genetic one. We investigated which cognitive and sensorimotor functions are associated with the brain regions where ACE2/TMPRSS2 is overexpressed, hypothesising that they might be particularly affected by the infection. Furthermore, overexpressed genes in these regions are likely to be impacted by COVID-19. This general understanding is crucial to establish the potential neurological manifestations of the infection. Data on mRNA expression levels of genes were provided by the Allen Institute for Brain Science (AIBS), and the localisation of brain functions by the LinkRbrain platform. The latter was also used to analyze the spatial overlap between ACE2/TMPRSS2 overexpression, and either function-specific brain activations or regional overexpression of other genes. The characterisation of these overexpressed genes was based on the GeneCards platform and the gene GSE164332 from the Gene Expression Omnibus database. We analysed the cognitive and sensorimotor functions whose role might be impaired, of which 88 have been categorised into seven groups: memory and recollection, motor function, pain, lucidity, emotion, sensory, and reward. Furthermore, we categorised the genes showing a significant increase in concentration of their mRNAs in the same regions where ACE2/TMPRSS2 mRNA levels are the highest. Eleven groups emerged from a bibliographical research: neurodegenerative disease, immunity, inflammation, olfactory receptor, cancer/apoptosis, executive function, senses, ischemia, motor function, myelination, and dependence. The results of this exploration could be in relation to the neurological symptoms of COVID-19. Furthermore, some genes from peripheral blood are already considered as biomarker of COVID-19. This method could generate new hypotheses to explore the neurological manifestations of COVID-19.
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