Neurological manifestations in COVID-19: how relevant is this association?

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was first reported in December 2019 in an outbreak occurring in Wuhan, China and has spread rapidly all over the word causing a global pandemic with approximately 129 million confirmed cases and more than 2.8 million deaths worldwide as of April 2nd, 2021. With the increasing number of people affected by this disease, it has become early apparent that SARS-CoV-2 may also affect the nervous system. EVIDENCE ACQUISITION: A great number of case reports, case series and review, often incomplete and not-peer- reviewed, about the observation of neurological symptoms in coronavirus disease-19 (COVID-19) have been published to date. In this review, we have tried to summarize the most recent evidences about the main neurological syndrome as- sociated to the infection: delirium/confusion, encephalitis, Guillain-Barré Syndrome (GBS) and ischemic stroke. EVIDENCE SYNTHESIS: From the huge amount of literature published in the last year, it appears that the neurological involvement of nervous system in COVID-19 is a relatively rare event as compared to the lung damage, but it is one of the most frequent extra-pulmonary complications. A supposed direct invasion of the nervous system, a para-infectious or post-infectious immune-mediated disease, or simply post-systemic effects of the viral infection, have been proposed as the main mechanisms. CONCLUSIONS: Encephalopathy and stroke are the most serious and common syndromes associated with COVID-19, mostly related to the inflammatory and hypercoagulable status, whereas available data suggest a post-infectious immune mediated mechanism for SARS-CoV-2 related GBS. However, more extensive epidemiological and histopathological studies are warranted to confirm the casualty of this latter association