Severe disease MESHD and uremia MESHD are risk factors for neurological complications of coronavirus disease MESHD-2019 (COVID-19). An in-depth analysis of a case series was conducted to describe the neurological manifestations of patients with COVID-19 and gain pathophysiological insights that may guide clinical decision-making – especially with respect to the cytokine release syndrome MESHD (CRS). Extensive clinical, laboratory, and imaging phenotyping was performed in five patients. Neurological presentation included confusion MESHD confusion HP, tremor MESHD tremor HP, cerebellar ataxia MESHD ataxia HP, behavioral alterations, aphasia MESHD aphasia HP, pyramidal syndrome MESHD, coma MESHD coma HP, cranial nerve palsy, dysautonomia, and central hypothyroidism HP hypothyroidism MESHD. Neurological disturbances were remarkably accompanied by laboratory evidence of CRS. SARS-CoV-2 was undetectable in the cerebrospinal fluid. Hyperalbuminorachy and increased levels of the astroglial protein S100B were suggestive of blood SERO-brain barrier (BBB) dysfunction. Brain MRI findings comprised evidence of acute leukoencephalitis (n = 3, of whom one with a hemorrhagic form), cytotoxic edema MESHD edema HP mimicking ischemic stroke HP stroke MESHD (n = 1), or normal results (n = 2). Treatment with corticosteroids and/or intravenous immunoglobulins was attempted – resulting in rapid recovery from neurological disturbances in two cases. Patients with COVID-19 can develop neurological manifestations that share clinical, laboratory, and imaging similarities with those of chimeric antigen receptor-T cell-related encephalopathy HP. The pathophysiological underpinnings appear to involve CRS, endothelial activation, BBB dysfunction, and immune-mediated mechanisms.