Neurotropic SARS-CoV-2: Causalities and Realities

Abstract

Evidences for the dysfunctions of central nervous system (CNS) caused by SARS-CoV-2 infection have accumulated since the beginning of pandemic. The clinical and experimental evidences on viral entry routes to CNS lead to several open questions. While the neurological impairments caused by the virus stay as a reality under Long COVID, dissecting the causality underlying these problems continues to be an intensely studied topic. Extensive reports of olfactory dysfunctions including anosmia, hyposmia, and parosmia due to infections during 2020–2021, led to the hypothesis of virus’ CNS invasion through the olfactory nerve. Some of the investigations using animal models of cellular factors mediating the viral entry also suggest potential neurotropism. Conversely, recent studies proved the absence of viral particles in olfactory sensory neurons and olfactory bulb, hence leading to the deliberation on viral entry route. Here, we summarize the findings on the debated neurotropic characteristics of the virus, including clinical observations and the results from animal models. Further, we emphasize on the need of tracking olfactory and cognitive fitness in the post-COVID-19 era.