Neurological manifestations of COVID-19 and other coronavirus infections: A systematic review

Abstract

Background: Increasing research reports neurological manifestations of COVID-19 patients. SARS-CoV-2 shares homology with other human coronaviruses that have also had nervous system involvement.

Objective: To review the neurological aspects of SARS-cov2 and other coronavirus, including transmission pathways, mechanisms of invasion into the nervous system, and mechanisms of neurological disease.

Methods: We conducted a systematic review of articles in PubMed, SCOPUS and EMBASE data bases. Reviewed evidence is presented in sections of this manuscript which includes pathogenesis, neuro-invasion, encephalitis, Guillain-Barré, ADEM, multiple sclerosis, polyneuropathy, and cerebrovascular disease.

Results: A total 67 studies were included in the final analysis of experimental studies, case reports, series of cases, cohort studies, and systematic reviews related to neurological manifestations of SARS- CoV-2 and other human coronavirus infections. The SARS-CoV-2 receptor is expressed in the nervous system. Common reported symptoms included hyposmia, headaches, weakness, altered consciousness. Encephalitis, demyelination, neuropathy, and stroke have been associated with COVID-19. Infection through the cribriform plate and olfactory bulb and dissemination through trans-synaptic transfer are some of the mechanisms proposed. Invasion of the medullary cardiorespiratory center by SARS-CoV-2 may contribute to the refractory respiratory failure observed in critically-ill COVID-19 patients.

Conclusion: An increasing number of reports of COVID-19 patients with neurological disorders add to emergent experimental models with neuro-invasion as a reasonable concern that SARS-CoV-2 is a new neuropathogen. How it may cause acute and chronic neurologic disorders needs to be clarified in future research.

Keywords: COVID-19; Coronavirus; Encephalitis; Neurological manifestations; SARS-CoV-2.

Fig. 1

MRI sequence of images from a patient with suspected COVID-19 associated acute necrotizing hemorrhagic encephalopathy. A. T2 FLAIR image with bilateral thalamic hyperintensity and surrounding edema. B. T2 image revealing bilateral thalamic hyperintensity. C. SWI reveals evidence of bilateral thalamic hemorrhage. D. T2 image with post contrast ring enhancement lesions in bilateral thalami. Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19–associated Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features. Radiology 2020:201187. doi:https://doi.org/10.1148/radiol.2020201187. Copyright Radiological Society of North America 2020.