Multi-Data Integration Towards a Global Understanding of the Neurological Impact of Human Brain Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Abstract

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.