Neurotropic SARS-CoV-2: Causalities and Realities

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

Persistent olfactory learning deficits during and post-COVID-19 infection

Quantifying olfactory impairments can facilitate early detection of Coronavirus disease 2019 (COVID-19). Despite being a debated topic, many reports provide evidence for the neurotropism of SARS-CoV-2. However, a sensitive, specific, and accurate non-invasive method for quantifying persistent neurological impairments is missing to date. To quantify olfactory detectabilities and neurocognitive impairments in symptomatic COVID-19 patients during and post-infection periods, we used a custom-built olfactory-action meter (OAM) providing accurate behavioral readouts. Ten monomolecular odors were used for quantifying olfactory detectabilities and two pairs of odors were employed for olfactory matching tests. We followed cohorts of healthy subjects, symptomatic patients, and recovered subjects for probing olfactory learning deficits, before the Coronavirus Omicron variant was reported in India. Our method identifies severe and persistent olfactory dysfunctions in symptomatic patients during COVID-19 infection. Symptomatic patients and recovered subjects showed significant olfactory learning deficits during and post-infection periods, 4–18 months, in comparison to healthy subjects. On comparing olfactory fitness, we found differential odor detectabilities and olfactory function scores in symptomatic patients and asymptomatic carriers. Our results indicate probable long-term neurocognitive deficits in COVID-19 patients imploring the necessity of long-term tracking during post-infection period. Differential olfactory fitness observed in symptomatic patients and asymptomatic carriers demand probing mechanisms of potentially distinct infection routes