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  • Updated 03.01.2024
  • Released 04.10.2020
  • Expires For CME 03.01.2027

Neurologic complications of coronavirus infections


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 four genera: alpha, beta, gamma, and delta. The alpha and beta coronaviruses primarily infect mammals, gamma coronaviruses primarily infect birds, and delta coronaviruses infect both mammals and birds. 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 (18). To date, seven human coronaviruses have been identified (Table 1). SARS and SARS-CoV-2 are thought to have originated from bats (38). They use the “spike proteins” to attach to angiotensin-converting enzyme receptor type 2 (ACE2), which is highly expressed in the respiratory tract. ACE2 receptors are also known to be expressed in both neurons and glia in several CNS areas, most notably in the choroid plexus and the thalamus. Several strains of SARS-CoV-2 have been identified. Currently, the most predominant strain is the Omicron strain. There does not appear to be any major difference in the neurotropism or neurovirulence between the various strains.

Table 1. Types of Human Coronaviruses and Their Receptors

Alpha Coronaviruses






Beta Coronaviruses








9-O-acetylsialic acid plus other sialoglycan-based receptors


9-O-acetylsialic acid

ACE=angiotensin converting enzyme; hAPN=human aminopeptidase N (CD13); DPP4=dipeptidyl peptidase 4

The virus has four main structural proteins: Spike (S)-protein is a trimeric protein that mediates attachment to the host receptor and is made of two separate polypeptides called S1 (binding domain) and S2 (stalk) (10). 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 SARS-CoV-2 virus was first discovered in Wuhan, China, in December 2019, and spread to every country in the world, paralyzed the global economy, devastated health care systems, and sent large populations into isolation. The clinical syndrome caused by SARS-CoV-2 has been termed “COVID-19.” The first confirmed case in the United States was reported on January 20, 2020 (09). As of December 17, 2023, more than 690 million persons worldwide had confirmed infections, with more than 5,000,000 deaths (41).

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