Project

It is increasingly clear that SARS-CoV-2 infection does not only affect the airways, but also the central nervous system (CNS) by interfering with neurons, glial cells, and the immune response in the brain, sometimes leading to long-lasting neurological signs, including anosmia and anxio-depressive symptoms. These and other persistent symptoms constitute a new entity that is currently called Long-COVID or Post-Acute COVID-19 Syndrome (PACS), however, it still lacks definitive diagnostic criteria and a universally accepted definition, as well a fully comprehensive view of its causative mechanisms. Our working hypothesis is that SARS-CoV-2 and/or the related inflammatory response can trigger a central mechanism in the CNS leading to the persistence of symptoms. The persistence of virus (or viral components, in particular viral RNA) along with the persistence of inflammation in the CNS may be an underlying cause for the occurrence of persistent symptoms in long COVID patients. Consequently, our main objective is to understand the origin and the mechanisms responsible for the persistent neurological symptoms such as long-term anosmia/ageusia or anxio-depressive symptoms post- SARS-CoV-2 infection, and we will focus on how viral neuroinvasion, neuroinflammation and/or signal transmitted by the neural route (lung-brain or visceral-brain axis) account for long-term post COVID-19 CNS alterations. At the end, the LongNeuroCOVID project should lead to several impactful results. From the scientific point of view, this work will improve the understanding of the general mechanisms involved in the spatio-temporal dynamics of SARS-CoV-2 infection, from entry in the CNS to causing long-term inflammation and CNS alterations. Describing these fundamental mechanisms should be of broader interest to the scientific community, as these results may be applicable to other, less understood, neuroinvasive pathogens.