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

Abstract

Objective: To describe the main neurological manifestations related to coronavirus infection in humans.

Methodology: A systematic review was conducted regarding clinical studies on cases that had neurological manifestations associated with COVID-19 and other coronaviruses. The search was carried out in the electronic databases PubMed, Scopus, Embase, and LILACS with the following keywords: "coronavirus" or "Sars-CoV-2" or "COVID-19" and "neurologic manifestations" or "neurological symptoms" or "meningitis" or "encephalitis" or "encephalopathy," following the Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results: Seven studies were included. Neurological alterations after CoV infection may vary from 17.3% to 36.4% and, in the pediatric age range, encephalitis may be as frequent as respiratory disorders, affecting 11 % and 12 % of patients, respectively. The Investigation included 409 patients diagnosed with CoV infection who presented neurological symptoms, with median age range varying from 3 to 62 years. The main neurological alterations were headache (69; 16.8 %), dizziness (57, 13.9 %), altered consciousness (46; 11.2 %), vomiting (26; 6.3 %), epileptic crises (7; 1.7 %), neuralgia (5; 1.2 %), and ataxia (3; 0.7 %). The main presumed diagnoses were acute viral meningitis/encephalitis in 25 (6.1 %) patients, hypoxic encephalopathy in 23 (5.6 %) patients, acute cerebrovascular disease in 6 (1.4 %) patients, 1 (0.2 %) patient with possible acute disseminated encephalomyelitis, 1 (0.2 %) patient with acute necrotizing hemorrhagic encephalopathy, and 2 (1.4 %) patients with CoV related to Guillain-Barré syndrome.

Conclusion: Coronaviruses have important neurotropic potential and they cause neurological alterations that range from mild to severe. The main neurological manifestations found were headache, dizziness and altered consciousness.

Keywords: ACE2, angiotensin converting enzyme 2; ADEM, acute disseminated encephalomyelitis; ANHE, acute necrotizing hemorrhagic encephalopathy; BBE, Bickerstaff’s encephalitis; COVID-19; COVID-19, coronavirus disease 2019; CoV, coronavirus; Coronavirus; DPP4, dipeptidil peptidase 4; Encephalopathy; G-CSF, granulocyte colony stimulating factor (G-CSF); GBS, Guillain-Barré syndrome; GM-CSF, granulocyte-macrophage colony-stimulating factor; HCoV, Human coronavirus; HCoV-229E, Human coronavirus 229E; HCoV-OC43, Human coronavirus OC43; ICU, intensive care unit; IL, interleukin; MCP-1, monocyte chemoattractant protein-1; MERS, Middle East respiratory syndrome; MERS-CoV, Middle East respiratory syndrome coronavirus; Neurologic manifestations; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; SARS, severe acute respiratory syndrome; SARS-CoV-2; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SARS‐CoV, severe acute respiratory syndrome coronavirus; βCoV, betacoronavírus.

Fig. 1

Flowchart summarizing the search strategy for studies. Adapted from Moher et al. (2009).