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Event: 1841

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help


Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Organ term

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
Sars-CoV-2 causes encephalitis AdverseOutcome Agnes Aggy (send email) Under development: Not open for comment. Do not cite Under Development
elavl3, sox10, mbp induced neuronal effects AdverseOutcome Brendan Ferreri-Hanberry (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
human Homo sapiens High NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
Adults High

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Mixed High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Encephalitis by definition is an inflammation of the brain tissue, most commonly caused by viral infections, and in some rare cases it can be caused by bacteria or even fungi. There are two main types of encephalitis: primary and secondary, with primary occurring when a virus directly infects the brain and the spinal cord. On the other hand, secondary encephalitis as a consequence of an infection occurring elsewhere in the body that then spread to the brain (Johnson, 2018).

Several causes may cause encephalitis, but the most common is a viral infection, and can be characterized by mild or severe flu-like symptoms, possibly causing confused thinking, seizures, or problems with movement or with senses, such as sight or hearing. In some cases, encephalitis can be life-threatening, and for this reason timely diagnosis and treatment are essential (Mayo, 2021).

Viral encephalitis refers to inflammatory lesions in the brain parenchyma caused by pathogens, including neuronal damage and nerve tissue lesions. It is characterized by acute onset, and common symptoms include headache, fever (mainly high fever), vomiting, convulsions, and consciousness disorders (Ellul and Solomon, 2018).

Encephalitis in the context of COVID19

Among various neurological adverse outcomes, SARS-CoV and SARS-CoV-2 can cause encephalitis (Moriguchi T et al. 2020; Efe et al. 2020; Najjar et al. 2020; Wu and Tang 2020; Bohmwald K, et al. 2020; Tsai LK et al. 2005; Xiang P. et al., 2020; Pilotto A et al. 2019; Ye M., et al. 2020; Das G, et al. 2020). Indeed, meningitis/meningoencephalitis has been observed in COVID19 patients (Iaconetta G et al. 2020). For instance, Moriguchi et al. have described SARS-CoV-2 encephalitis in a 24-year old man, 10 days after developing COVID19 symptoms, characterized by headache, fatigue, fever, and consciousness disturbance, and with MRI showing hyperintense signal changes in the hippocampus with slight hippocampal atrophy (Moriguchi T et al. 2020).

Early diagnosis of viral encephalitis is critical. In the ongoing pneumonia epidemic, the treatment team of Beijing Ditan Hospital confirmed the presence of SARS-CoV-2 in the cerebrospinal (CSF) fluid of patients with COVID-19 by genome sequencing, thereby clinically verifying viral encephalitis (Xiang et al., 2020). This provided a solid basis for CoV causing encephalitis.

CSF of COVID19 patients with encephalitis/meningoencephalitis often shows pleocytosis and elevated total protein and NfL levels (Espíndola et al. 2020) (Koralnik et al. 2020).

In SARS-CoV-2 infected patients with neurological manifestations, CSF pleocytosis is associated with para- or post-infectious encephalitis and polyradiculitis. Anti-GD1b and anti-Caspr2 autoantibodies can be identified in certain cases, raising the question of SARS-CoV-2-induced secondary autoimmunity (Guilmot et al., 2020).

Intracranial inoculation of murine coronavirus (mouse hepatic virus, MHV), induces optic neuritis and focal encephalitis leading to chronic demyelination in mice (Shindler KS, et al. 2008).

SARS-CoV responsible for the 2002–2004 outbreak was reported to induce encephalitis, along with polyneuropathy and ischemic stroke (Tsai et al. 2005).

Autopsy results of patients with SARS showed ischemic neuronal damage and demyelination. Viral RNA was detected in brain tissue, particularly accumulating in and around the hippocampus (Gu J, et al. 2005).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Encephalitis may be detected through the following diagnostic tests (

  • Magnetic resonance imaging (MRI)
  • Computed tomography scan (CT or CAT scan)
  • Blood tests
  • Urine and stool tests
  • Electroencephalogram (EEG)
  • Spinal tap (lumbar puncture)
  • Brain biopsy
  • Intracranial pressure monitoring (ICP), measuring the pressure inside the skull. If there is a severe brain injury, head surgery, brain infection, or other problems, the brain may swell.

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Regulatory Significance of the Adverse Outcome

An AO is a specialised KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help


List of the literature that was cited for this KE description. More help

Bohmwald K, et al. Neurologic Alterations Due to Respiratory Virus Infections. Front Cell Neurosci. 2018 Oct 26;12:386.

Das G, et al. Neurological Insights of COVID-19 Pandemic. ACS Chem Neurosci. 2020 May 6; 11(9):1206-1209.

Efe et al. COVID-19-Associated Encephalitis Mimicking Glial Tumor. World Neurosurg. 2020 Aug; 140: 46–48.

Ellul M., Solomon T. Acute encephalitis - diagnosis and management. Clin. Med. (Lond) 2018;18(2):155–159.

Encephalitis, available at:

Espíndola OM et al. Patients with COVID-19 and neurological manifestations show undetectable SARS-CoV-2 RNA levels in the cerebrospinal fluid. Int J Infect Dis. 2020 Jul;96:567-569.

Gu J, et al. Multiple organ infection and the pathogenesis of SARS. J Exp Med. 2005;202:415–424.

Guilmot A, et al. Immune-mediated neurological syndromes in SARS-CoV-2-infected patients. J Neurol. 2020 Jul 30;1-7.

Iaconetta G et al. Meningoencephalitis Associated with SARS-Coronavirus-2. Transl Med UniSa. 2020 Dec 31;23:42-47.

Johnson S. What is encephalitis? Healthline, 2018 available at

Koralnik et al. COVID-19: A Global Threat to the Nervous System. Ann Neurol. 2020 Jul;88(1):1-11.

Mayo Clinic, Encephalitis. 2021, available at

Moriguchi T et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis. 2020;94:55–58.

Najjar et al. Central nervous system complications associated with SARS-CoV-2 infection: integrative concepts of pathophysiology and case reports. J Neuroinflammation. 2020 Aug 6;17(1):231.

Pilotto A et al. Steroid-Responsive Encephalitis in Coronavirus Disease 2019. Ann Neurol. 2020 Aug;88(2):423-427.

Shindler KS, et al. Experimental optic neuritis induced by a demyelinating strain of mouse hepatitis virus. J Virol. 2008 Sep; 82(17):8882-6.

Tsai L.-K., et al. Neurological manifestations in severe acute respiratory syndrome. Acta Neurol Taiwanica. 2005;14:113–119

Wu J. and Tang Y. Revisiting the Immune Balance Theory: A Neurological Insight Into the Epidemic of COVID-19 and Its Alike. Front Neurol. 2020 Oct 15;11:566680.

Xiang P., et al. First case of 2019 novel coronavirus disease with Encephalitis. ChinaXiv. 2020;T202003:00015.

Ye M., et al. Encephalitis as a clinical manifestation of COVID-19. Brain, Behavior, and Immunity. 2020 S0889159120304657.