COVID-19-associated encephalitis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Wajeeha Aiman, M.D.[2]

Synonyms and keywords: Encephalitis covid-19

Overview

Encephalitis is inflammation of the brain parenchyma and it is commonly caused by viruses. COVID-19 is a virus related to the severe acute respiratory syndrome coronavirus (SARS-CoV) group and named as SARS-CoV-2.

Historical Perspective

Covid-19 associated encephalitis was first discovered by Moriguchi T. et al. a Japanese critical care physician in late February 2020 during the pandemic of SARS-Coronavirus-2: SARS-CoV-2.^[1]^[2]

The association between COVID-19 and encephalitis was made during this pandemic started in December in Wuhan, China and named as Wuhan coronavirus.^[3]
In March 2020, Dr. Ali A. was the first to discover the association between COVID-19 and neurological diseases e.g. encephalitis. He made a clinical diagnosis along with his team and then MRI used to diagnose the disease.^[4]
In January 2020, Chinese doctors confirmed the first case of encephalitis due to COVID-19 in a 56 year old male and they conducted gene sequencing on cerebrospinal fluid (CSF) samples and confirmed the novel virus inside brain, but it was not published.
There have been several outbreaks of SARS and MERS.

Classification

There is no established system for the classification of COVID-19 associated encephalitis.
Based on the duration of symptoms, this disease is classified as acute.

Pathophysiology

The exact pathogenesis of COVID-19 encephalitis is not fully understood.

It is thought that this viral encephalitis is the result of multiple pathophysiologic pathways.

SARS-CoV-2 Entry via Nose

Olfactory Epithelium

Olfactory Bulb

ACE2

Direct Injury due to Infection

Immune Injury

Hypoxic Injury

Hypercoagulability

Viral Encephalitis

ACE2: Angiotensin converting enzyme receptor 2 is present in multiple organs e.g. lungs, brain, and kidney, etc.
Hypercoagulability: With elevated D-dimer
Immune injury: Cytokine activation and vascular involvement.
Direct injury: Due to hematogenous and neuronal pathway involvement.
Hypoxic injury: Due to anaerobic metabolism.^[5]

Causes

Coronavirus disease 2019 (COVID-19) associated encephalitis is caused by SARS-CoV-2.

To read more about this virus, click here.

Differentiating COVID-19-associated encephalitis from other Diseases

COVID-19-associated encephalitis must be differentiated from other diseases that cause fever, headache, and altered mental status with or without cough, such as

Case courtesy of Dr. Daniel J Bell, Radiopaedia.org, rID: 74536

Risk Factors

Common risk factors in the development of COVID-19-associated encephalitis may be occupational, environmental, and genetic.

Risk factors for this disease are the same as for COVID-19.
Auto-immune syndromes might be at higher risk of developing this disease due to immunosuppressive therapy.^[7]

Risk factors for COVID-19-associated encephalitis
Autoimmune disease	Immunosuppression
Multiple sclerosis	Interferon beta Glatiramer Corticosteroids
Myasthenia gravis	Corticosteroids
Neuromyelitis optica	Monoclonal antibody
Sarcoidosis	Corticosteroids Methotrexate Azathioprine
Sickle cell disease (SCD)	Crizanlizumab

Screening

There is insufficient evidence to recommend routine screening for COVID-19-associated encephalitis.

Complications

If left untreated, patients with COVID-19-associated encephalitis may progress to damage the brain and cause:

Encephalitis

Memory loss

Epilepsy

Personality changes

Hearing/vision loss

Coma/Death

Diagnosis

History and Symptoms

The majority of patients with COVID-19-associated encephalitis present with respiratory symptoms. e.g. cough, shortness of breath etc.
Three cases reported till now has specific clinical manifestations:


Patient No.	Early symptoms	Later presentation	GCS
1. 24-year-old man from Japan^[2]	Headache, Fever, Fatigue	Worsening headache, Sore throat. (Day 5) Impaired consciousness and transient generalized seizure, (Day 9)	E4V1M1
2. 35-year-old woman from Turkey^[6]	Flu like symptoms	Headache, nausea, dizziness, and drug-refractory seizures.	E4V5M6
3. 31-year-old African American woman^[8]	SCD patient with dyspnea	Paralysis and sedation (Day 13) Comatose (Day 15) and death (Day 16)	E0V0M0

Physical Examination

Laboratory Findings

Treatment

Medical Therapy

Surgery

References

↑ Velavan TP, Meyer CG (2020). "The COVID-19 epidemic". Trop Med Int Health. 25 (3): 278–280. doi:10.1111/tmi.13383. PMC 7169770 Check |pmc= value (help). PMID 32052514 Check |pmid= value (help).
↑ ^2.0 ^2.1 ^2.2 Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J; et al. (2020). "A first case of meningitis/encephalitis associated with SARS-Coronavirus-2". Int J Infect Dis. 94: 55–58. doi:10.1016/j.ijid.2020.03.062. PMC 7195378 Check |pmc= value (help). PMID 32251791 Check |pmid= value (help).
↑ Riou J, Althaus CL (2020). "Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020". Euro Surveill. 25 (4). doi:10.2807/1560-7917.ES.2020.25.4.2000058. PMC 7001239 Check |pmc= value (help). PMID 32019669 Check |pmid= value (help).
↑ Asadi-Pooya AA, Simani L (2020). "Central nervous system manifestations of COVID-19: A systematic review". J Neurol Sci. 413: 116832. doi:10.1016/j.jns.2020.116832. PMC 7151535 Check |pmc= value (help). PMID 32299017 Check |pmid= value (help).
↑ Baig AM (2020). "Neurological manifestations in COVID-19 caused by SARS-CoV-2". CNS Neurosci Ther. 26 (5): 499–501. doi:10.1111/cns.13372. PMC 7163592 Check |pmc= value (help). PMID 32266761 Check |pmid= value (help).
↑ ^6.0 ^6.1 Efe IE, Aydin OU, Alabulut A, Celik O, Aydin K (2020). "COVID-19-Associated Encephalitis Mimicking Glial Tumor". World Neurosurg. 140: 46–48. doi:10.1016/j.wneu.2020.05.194. PMC 7256557 Check |pmc= value (help). PMID 32479911 Check |pmid= value (help).
↑ Nath A (2020). "Neurologic complications of coronavirus infections". Neurology. 94 (19): 809–810. doi:10.1212/WNL.0000000000009455. PMID 32229625 Check |pmid= value (help).
↑ Benameur K, Agarwal A, Auld SC, Butters MP, Webster AS, Ozturk T; et al. (2020). "Encephalopathy and Encephalitis Associated with Cerebrospinal Fluid Cytokine Alterations and Coronavirus Disease, Atlanta, Georgia, USA, 2020". Emerg Infect Dis. 26 (9). doi:10.3201/eid2609.202122. PMID 32487282 Check |pmid= value (help).

Template:WikiDoc Sources

[pmid32052514-1] Velavan TP, Meyer CG (2020). "The COVID-19 epidemic". Trop Med Int Health. 25 (3): 278–280. doi:10.1111/tmi.13383. PMC 7169770 Check |pmc= value (help). PMID 32052514 Check |pmid= value (help).

[pmid32251791-2] 2.0 ^2.1 ^2.2 Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J; et al. (2020). "A first case of meningitis/encephalitis associated with SARS-Coronavirus-2". Int J Infect Dis. 94: 55–58. doi:10.1016/j.ijid.2020.03.062. PMC 7195378 Check |pmc= value (help). PMID 32251791 Check |pmid= value (help).

[pmid32019669-3] Riou J, Althaus CL (2020). "Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020". Euro Surveill. 25 (4). doi:10.2807/1560-7917.ES.2020.25.4.2000058. PMC 7001239 Check |pmc= value (help). PMID 32019669 Check |pmid= value (help).

[pmid32299017-4] Asadi-Pooya AA, Simani L (2020). "Central nervous system manifestations of COVID-19: A systematic review". J Neurol Sci. 413: 116832. doi:10.1016/j.jns.2020.116832. PMC 7151535 Check |pmc= value (help). PMID 32299017 Check |pmid= value (help).

[pmid32266761-5] Baig AM (2020). "Neurological manifestations in COVID-19 caused by SARS-CoV-2". CNS Neurosci Ther. 26 (5): 499–501. doi:10.1111/cns.13372. PMC 7163592 Check |pmc= value (help). PMID 32266761 Check |pmid= value (help).

[pmid32479911-6] 6.0 ^6.1 Efe IE, Aydin OU, Alabulut A, Celik O, Aydin K (2020). "COVID-19-Associated Encephalitis Mimicking Glial Tumor". World Neurosurg. 140: 46–48. doi:10.1016/j.wneu.2020.05.194. PMC 7256557 Check |pmc= value (help). PMID 32479911 Check |pmid= value (help).

[pmid32229625-7] Nath A (2020). "Neurologic complications of coronavirus infections". Neurology. 94 (19): 809–810. doi:10.1212/WNL.0000000000009455. PMID 32229625 Check |pmid= value (help).

[pmid32487282-8] Benameur K, Agarwal A, Auld SC, Butters MP, Webster AS, Ozturk T; et al. (2020). "Encephalopathy and Encephalitis Associated with Cerebrospinal Fluid Cytokine Alterations and Coronavirus Disease, Atlanta, Georgia, USA, 2020". Emerg Infect Dis. 26 (9). doi:10.3201/eid2609.202122. PMID 32487282 Check |pmid= value (help).

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