A Systematic Review on Neurological Aspects of COVID-19: Exploring the Relationship Between COVID-19-Related Olfactory Dysfunction and Neuroinvasion

OBJECTIVES: To identify neurological aspects of Coronavirus disease 2019 (COVID-19) and to investigate COVID-19 infected patients with and without olfactory dysfunction in relation to polymerase chain reaction (PCR) assay results for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in the cerebrospinal fluid (CSF). METHODS: PubMed and EMBASE databases were searched until March 26, 2021, for observational studies with COVID-19 patients that had performed CSF PCR assay due to the neurologic symptom and reported anosmia status. RESULTS: Initially, 2,387 studies were identified;167 studies performed SARS-CoV-2 CSF PCR assay, of which our review comprised 45 observational studies that conducted CSF PCR assay for SARS-CoV-2 in 101 patients and reported anosmia status in 55 of 101 patients. Central and peripheral neurological manifestations observed in COVID-19 patients were diverse. The most common neurological diagnoses were Guillain-Barré syndrome (GBS) and its variants (24%), followed by encephalopathy (21%). The SARS-CoV-2 PCR assay was positive in only four CSF samples, of which two patients had olfactory dysfunction while the others did not. CONCLUSIONS: The neurological spectrum of COVID-19 is diverse, and direct neuroinvasion of SARS-CoV-2 is rare. The neuroprotection against SARS-CoV-2 in COVID-19 patients with anosmia is controversial, as an equal number of patients with and without olfactory dysfunction had positive CSF PCR results for SARS-CoV-2 in our study, and further studies are required to provide more insight into this topic.