COVID-19 Neuropathology: disentangling the role of SARS-CoV-2 infection in neurological manifestations and neurodegenerative diseases

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel strain of the Coronavirus Family (CoV) responsible for the disease known as Coronavirus Disease 2019 (COVID19). Although manifesting primarily as a respiratory disease, neurological manifestations are common in COVID-19, either presenting as new symptoms or disorders (e.g., stroke, encephalitis, Guillain-Barré syndrome) or as the exacerbation of pre-existing symptoms of known chronic neurological conditions, with particular regard to neurodegenerative diseases. These observations, along with the detection of the virus in post-mortem tissue and cerebrospinal fluid raise the question of whether SARS-CoV-2 possesses neurotropic properties, or observed neurological manifestations are rather to be ascribed to the effects of systemic infection, ongoing cytokine storm, inflammation and hypoxia. Furthermore, the burden of COVID-19 on the autonomic nervous system and on peripheral chemoceptors may represent a so far undervalued mechanism for a vicious circle between COVID-19 and the frequent comorbidities affecting patients susceptible to severe or even fatal manifestations of the disease. Our aim was to evaluate the pathological mechanisms underlying neurological manifestations in COVID-19, and assess the short- and (possible) long-term consequences of COVID-19 on the nervous system. For this purpose, we present a collection of seven peer-reviewed articles which aim to define the role of SARS-CoV-2 and COVID-19 on the peripheral nervous system, on peripheral chemoreceptorial structures, and on the central nervous system. While particular focus has been given to post-mortem investigations and neuropathology underlying COVID-19, we also evaluated the link between in-vivo neurological manifestations and viral genomic variants to further characterize the disease.