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], Fahimeh Shojaei, M.D., Muhammad Adnan Haider, M.B.B.S.[3]

Synonyms and keywords: Encephalitis covid-19


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. 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. The association between COVID-19 and encephalitis was made early in the pandemic in the Wuhan province of China. There is no established system for the classification of COVID-19 associated encephalitis. The exact pathogenesis of COVID-19 encephalitis is not fully understood. COVID-19-associated encephalitis must be differentiated from other diseases that cause fever, headache, and altered mental status with or without cough.

Historical Perspective



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

Direct Injury due to Infection
Immune Injury
Hypoxic Injury
Viral Encephalitis


  • To read more about this virus, click here.
Case courtesy of Dr. Daniel J Bell,, rID: 74536

Differentiating COVID-19-associated encephalitis from other Diseases

  • For further information about the differential diagnosis, click here.
  • To view the differential diagnosis of COVID-19, click here.

Epidemiology and Demographics

Risk Factors

Risk factors for COVID-19-associated encephalitis
Autoimmune disease Immunosuppression
Multiple sclerosis Interferon beta



Myasthenia gravis Corticosteroids
Neuromyelitis optica Monoclonal antibody
Sarcoidosis Corticosteroids



Sickle cell disease (SCD) Crizanlizumab


Natural History, Complications, and Prognosis

Memory loss
Personality changes
Hearing/vision loss


Diagnostic Study of Choice

History and Symptoms

Common Symptoms

Less Common Symptoms

  • Clinical manifestation of 3 cases of COVID-19 associated encephalitis are shown below:
Patient No. Early symptoms Later presentation GCS Lab. Findings Specific Tests Imaging studies
24-year-old man from Japan[2] Headache,



Worsening headache, Sore throat. (Day 5)

Impaired consciousness and transient generalized seizure, (Day 9)

E4V1M1 WBCs and neutrophils


Clear and colorless fluid,

Pressure=320 mmH2O,

Cell count was 12/μL–10

mononuclear and 2 polymorphonuclear cells

RT-PCR of SARS-CoV-2 RNA was positive in CSF Brain MRI:

Hyperintensity in the right lateral ventricle's inferior horn along the wall,

pan-paranasal sinusitis.

In Wuhan, in a letter to editor, Ye M, reported COVID-19 associated encephalitis case in a male with laboratory finding [9] Fever



Confusion NA WBC count (3.3 × 109/L) and lymphopenia (0.8 × 109/L) Pressure=220 mmg

WBC (0.001 × 109/L)

protein (0.27 g/L)

sugar (3.14 mmol/L)

SARS-CoV-2 was positive on nasopharyngeal swab but negative on CSF testing

All other bacterial and viral causes of encephlitis were negative

  • skull CT was normal
  • chest CT showed multiple subpleural ground glass opacities
35-year-old woman from Turkey[10][11] whose COVID-19 associated encephalitis mimicking as glial tumor of CNS Flu like symptoms Headache, nausea, dizziness, and

drug-refractory seizures.

E4V5M6 NA NA RT-PCR and antibody tests positive Brain MRI: Hyperintensity in the left temporal lobe.

MR Spectroscopy: Decrease N-acetyl aspartate peak along with a marked elevated choline peak.

31-year-old African American woman[12] SCD patient with dyspnea Paralysis and sedation (Day 13)

Comatose (Day 15) and death (Day 16)

E0V0M0 NA Pressure=30cmH2O

115 nucleated cell /ml

7374 erythrocytes


Protein> 200mg/dl

RT=PCR for SARS-CoV-2 was positive in nasopharyngeal swab Brain MRI: Nonenhancing cerebral edema and restricted diffusion in the right cerebral hemisphere with brain herniation.

Physical Examination


Laboratory Findings



Echocardiography or Ultrasound

CT scan


Other Diagnostic Studies


Medical Therapy

The mainstays of medical therapy for viral encephalitis are:[10][13][2][14]

Symptomatic treatments:


Primary Prevention

Secondary Prevention


  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).
  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).
  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).
  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).
  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).
  6. Arabi YM, Balkhy HH, Hayden FG, Bouchama A, Luke T, Baillie JK; et al. (2017). "Middle East Respiratory Syndrome". N Engl J Med. 376 (6): 584–594. doi:10.1056/NEJMsr1408795. PMC 5362064. PMID 28177862.
  7. Tsai LK, Hsieh ST, Chang YC (2005). "Neurological manifestations in severe acute respiratory syndrome". Acta Neurol Taiwan. 14 (3): 113–9. PMID 16252612.
  8. Nath A (2020). "Neurologic complications of coronavirus infections". Neurology. 94 (19): 809–810. doi:10.1212/WNL.0000000000009455. PMID 32229625 Check |pmid= value (help).
  9. Ye M, Ren Y, Lv T (2020). "Encephalitis as a clinical manifestation of COVID-19". Brain Behav Immun. 88: 945–946. doi:10.1016/j.bbi.2020.04.017. PMC 7146652 Check |pmc= value (help). PMID 32283294 Check |pmid= value (help).
  10. 10.0 10.1 10.2 10.3
  11. 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).
  12. 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).
  13. Ueda R, Saito Y, Ohno K, Maruta K, Matsunami K, Saiki Y, Sokota T, Sugihara S, Nishimura Y, Tamasaki A, Narita A, Imamura A, Maegaki Y (May 2015). "Effect of levetiracetam in acute encephalitis with refractory, repetitive partial seizures during acute and chronic phase". Brain Dev. 37 (5): 471–7. doi:10.1016/j.braindev.2014.08.003. PMID 25174548.
  14. Nakano A, Yamasaki R, Miyazaki S, Horiuchi N, Kunishige M, Mitsui T (2003). "Beneficial effect of steroid pulse therapy on acute viral encephalitis". Eur. Neurol. 50 (4): 225–9. doi:10.1159/000073864. PMID 14634267.
  15. Panariello A, Bassetti R, Radice A, Rossotti R, Puoti M, Corradin M; et al. (2020). "Anti-NMDA receptor encephalitis in a psychiatric Covid-19 patient: A case report". Brain Behav Immun. 87: 179–181. doi:10.1016/j.bbi.2020.05.054. PMC 7255176 Check |pmc= value (help). PMID 32454137 Check |pmid= value (help).
  16. Dogan L, Kaya D, Sarikaya T, Zengin R, Dincer A, Akinci IO; et al. (2020). "Plasmapheresis treatment in COVID-19-related autoimmune meningoencephalitis: Case series". Brain Behav Immun. 87: 155–158. doi:10.1016/j.bbi.2020.05.022. PMC 7204750 Check |pmc= value (help). PMID 32389697 Check |pmid= value (help).

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