Neurological manifestations of COVID-19: a systematic review

Gaurav Nepal,Dong Ya Huang,Rajeev Ojha,Jayant Kumar Yadav,Gentle Sunder Shrestha,Zhi Lan Tu,Jessica Holly Rehrig,Yow Ka Shing,Gaurab Pokhrel

doi:10.1186/s13054-020-03121-z

Abstract

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global spread of coronavirus disease (COVID-19). Our understanding of the impact this virus has on the nervous system is limited. Our review aims to inform and improve decision-making among the physicians treating COVID-19 by presenting a systematic analysis of the neurological manifestations experienced within these patients.MethodsAny study, released prior to May 20, 2020, that reported neurological manifestations in patients infected by SARS-CoV-2 was systematically reviewed using the PRISMA (Preferred Reporting Items for Systemic review and Meta-Analysis) statement.ResultsOur systematic review included data from 37 articles: twelve retrospective studies, two prospective studies, and the rest case reports/series. The most commonly reported neurological manifestations of COVID-19 were myalgia, headache, altered sensorium, hyposmia, and hypogeusia. Uncommonly, COVID-19 can also present with central nervous system manifestations such as ischemic stroke, intracerebral hemorrhage, encephalo-myelitis, and acute myelitis, peripheral nervous manifestations such as Guillain-Barré syndrome and Bell’s palsy, and skeletal muscle manifestations such as rhabdomyolysis.ConclusionWhile COVID-19 typically presents as a self-limiting respiratory disease, it has been reported in up to 20% of patients to progress to severe illness with multi-organ involvement. The neurological manifestations of COVID-19 are not uncommon, but our study found most resolve with treatment of the underlying infection. Although the timeliness of this review engages current challenges posed by the COVID-19 pandemic, readers must not ignore the limitations and biases intrinsic to an early investigation.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global spread of coronavirus disease (COVID-19)
We evaluate various neurological manifestations reported in COVID19 patients and hypothesize their underlying pathophysiology
Experimental studies using transgenic mice suggest that SARS-CoV and MERS-COV may enter the central nervous system intranasally through the olfactory nerve

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global spread of coronavirus disease (COVID-19). Our review aims to inform and improve decision-making among the physicians treating COVID-19 by presenting a systematic analysis of the neurological manifestations experienced within these patients. Coronavirus disease (COVID-19) is caused by the novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. Since its recent discovery in Wuhan, China, coronavirus disease has spread across the world, leaving physicians challenged by its variable clinical manifestations. Most patients infected by SARS-CoV-2 have presented with a mild clinical course: beginning with fever and dry cough, progressing to a form of mild or moderate respiratory disease, and resolving without specific treatment [2]. Acute heart injury or failure, acute kidney injury, sepsis, disseminated intravascular coagulation, and lifethreatening metabolic derangements have all been reported in COVID-19 patients, among those with underlying comorbidities or advanced age [1, 3].

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