Neurological involvement in SARS-CoV-2 infection: A clinical systematic review

OBJECTIVE: Reports of neurological involvement during Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection course are increasingly described. The aim of this review is to provide a clinical approach of SARS-CoV-2 neurological complications based on the direct or indirect (systemic/immune-mediated) role of the SARS-CoV-2 in their genesis. METHODS: A review of the current literature has been carried out up to May 20th 2020 according to the PRISMA guidelines. All case series and reports of adult neurological manifestations associated to SARS-CoV-2 published in English were considered. Review and fundamental research studies on Coronaviruses neuroinvasive potential were analyzed to support pathogenic hypothesis and possible underlying mechanisms. Clinical patterns were subdivided into three groups according to putative underlying mechanisms: direct invasion of central or peripheral nervous system, systemic disorders leading to acute CNS injuries and post-infectious neurological syndromes (PINS). RESULTS: Sixteen case series and 26 case reports for a total of 903 patients were identified presenting with neurological involvement during SARS-CoV-2 infection. Hypo/anosmia and dys/ageusia were found in 826 patients and mainly attributed to direct viral invasion. Cerebrovascular complications occurred in 51 patients and related to viral infection associated systemic inflammation. PINS were described in only 26 patients. A wide heterogeneity of these reports emerged concerning the extension of the clinical examination and ancillary exams performed. CONCLUSIONS: Neurological complications of SARS-CoV-2 are mainly related to olfactory and gustatory sensory perception disorders through possible direct nervous system invasion while cerebrovascular disease and PINS are rare and due to distinct and indirect pathophysiological mechanisms.