Neurologic complications of coronavirus infections: knowns, unknowns, and who knows

Avindra Nath MD (

Dr. Nath of the National Institutes of Neurological Disorders and Stroke, National Institutes of Health has no relevant financial relationships to disclose.

Bryan Smith MD (

Dr. Smith of the National Institutes of Neurological Disorders and Stroke, National Institutes of Health has no relevant financial relationships to disclose.

John E Greenlee MD, editor. (Dr. Greenlee of the University of Utah School of Medicine has no relevant financial relationships to disclose.)
Originally released April 10, 2020; Expires April 10, 2023

Coronaviruses are enveloped viruses with a positive-sense single-stranded RNA genome. The word corona is derived from “crown,” which describes the spike-like proteins on its surface. They are classified as 4 genera: alpha, beta, gamma, and delta. The alpha, beta, and delta coronaviruses infect mammals, whereas delta and gamma coronaviruses infect avian species. However, the virus has the ability to jump between species, leading to the emergence of Middle East respiratory syndrome (MERS) caused by MERS-CoV, severe acute respiratory syndrome (SARS) caused by SARS-CoV-1, and COVID-19 caused by SARS-CoV-2, with deadly consequences (Li 2016). To date, 8 human coronaviruses have been identified (Table 1). SARS and SARS-CoV-2 are thought to have originated from bats (Chan et al 2020). They use the “spike proteins” to attach to angiotensin-converting enzyme receptor type 2 (ACE-2), which is highly expressed in the respiratory tract (Lu et al 2020).

Table 1. Types of Human Coronaviruses And Their Receptors











ACE=angiotensin converting enzyme; DPP4=Dipeptidyl peptidase 4

The virus has 4 main structural proteins: Spike (S)-protein is a trimeric protein that mediates attachment to the host receptor and is made of 2 separate polypeptides called S1 (binding domain) and S2 (stalk). The membrane protein is the most abundant structural protein in the virion. The envelope protein facilitates assembly and release of the virus. The ion channel activity in SARS-CoV envelope protein plays a critical role in pathogenesis. The N-protein constitutes the nucleocapsid that binds the viral RNA. The hemagglutinin-esterase protein is present in a subset of beta-coronaviruses and binds sialic acids on surface glycoproteins and contains acetyl-esterase activity (Li 2016). The neuropathogenesis of coronaviruses has been best studied in a mouse model infected with the mouse hepatitis virus.

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