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Viral Encephalitis Associated with COVID-19: A Review of the Literature and

Two Cases

Article in SSRN Electronic Journal · April 2020

DOI: 10.2139/ssrn.3573520

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 Viral encephalitis associated with COVID-19: a review of the

literature and two cases

Nadia M.T. Jebril a,b Page | 1

aSchool of Biological and Marine Sciences, Plymouth University, Drake Circus,
Plymouth PL4 8AA, United Kingdom.

bDepartment of Biology, College of Sciences for Women, University of Babylon, Iraq.

E-mail: nadia.jebril@students.plymouth.ac.uk

ORCID ID: 0000-0002-5368-2127

Abstract

Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infects the

human upper respiratory, causing coronavirus disease 2019 (COVID-19) with

symptoms of acute respiratory distress syndrome (ARDS). However, in susceptible

populations, such as immune-compromised individuals and the elderly, the symptoms

develop to more severe disease (e.g., pneumonia). For a few days now, data reported

in the neurological studies have also confirmed that SARS-CoV-2 has neuroinvasive

capacities, as it can spread from the respiratory tract to the nervous system (NS),

causing encephalitis. Compared to neuroinvasive human coronaviruses, SARS-CoV-

2 may damage the nervous system, causing neurological diseases. Opportunistic

human SARS-CoV-2 pathogens could be associated with the triggering or the

exacerbation of several neurological disorders whose etiology remains poorly

understood. In this review, details about human coronaviruses that have been linked

to the possibility of developing a disease of the nervous system were illustrated. Two

cases of viral encephalitis in patients diagnosed with COVID-19 were discussed in this

review: one patient presented with encephalopathy; the other patient with acute

hemorrhagic necrotizing encephalopathy.

Electronic copy available at: https://ssrn.com/abstract=3573520

Keywords: COVID-19, nervous system, encephalitis, human coronaviruses,

neuroinvasion, respiratory viral infection, SARS-CoV-2.

Introduction
Page | 2

COVID-19 was declared as a pandemic disease due to the rapid spread to the world.

SARS-CoV-2 infects the upper respiratory tract of the COVID-19 infected patients,

causing acute respiratory distress syndrome (ARDS) (Jebril, 2020b). Over the days,

like SARS-CoV and MERS-CoV, the SARS-CoV-2 have also been identified to cause

illnesses outside the respiratory tract, gastrointestinal symptoms (Chan et al., 2020)

and NS. Viruses can enter the NS through the hematogenous or neuronal retrograde

route, and infect target cells, neurons (Bale, 2015). The NS, a system of involved

cellular and molecular interactions, sustains life and orchestrates homeostasis. The

NS is not immune to acute, persistent, or latent viral infections, causing some

neurological disease. Viral encephalitis is the most prevalent virus known to NS

infection. Recently, two studies reported a possible complication of the presence of

SARS-CoV-2 within the human NS, mainly encephalopathy. Physical examination and

medical history can be used to diagnose encephalopathy, such as brain imaging (MRI

or CT images), which can show any swelling of the brain, cerebrospinal fluid (CSF), in

which any changes in this fluid can indicate infection and tenderness in the brain.

Electroencephalogram (EEG) records the brain's electrical activity, in which certain

abnormal patterns may indicate a diagnosis of encephalitis. In addition, biomedical

tests such as blood tests, urine tests, or swab from the throat can be shown for viruses

or other infectious causes.

Electronic copy available at: https://ssrn.com/abstract=3573520

Possible mechanisms of brain diseases by SARS-CoV-2

In the human respiratory system, a SARS-CoV-2 infection may cause a nasal

epithelium disorder, which also causes a large number of viruses to be released from
Page | 3
the lower side to the epithelium barrier and reach the bloodstream or lymph and spread

to other tissues, including the brain. HCoV has been found a pass through the

neuroepithelium and increase access to the olfactory bulb (OB) and eventually to other

regions of the brain (Desforges et al., 2020). Therefore, SARS-CoV-2 could use the

same route to penetrate the NS, as shown in Figure 1. On the other hand, SARS-CoV

has been found to infect myeloid cells (Spiegel, 2006) to influence the innate immunity

and to distribute to other tissues, including the NS. Therefore, SARS-CoV-2 could use

the alternative route (hematogenous) to penetrate the NS.

Figure 1. Possible mechanisms of brain diseases by SARS-CoV-2 through the

neuroepithelium and increase access to regions of the brain.

Electronic copy available at: https://ssrn.com/abstract=3573520

Human SARS-CoV-2 in the NS: possible associated neurological pathologies

Because of the neurogenic potential of virus types in humans and animals, it is often
Page | 4
suggested that a possible correlation exists between the presence of human

coronaviruses everywhere, causing human neurological diseases over the years. It is

now found that SARS-CoV-2 is not always narrowed to the upper respiratory tract and

that they can enter the NS. In the next sections, two cases of patients with

encephalopathy who were diagnosed with COVID-19 were discussed.

Case 1: Potential encephalopathy

The first case is a 74-year-old male with COVID-19 diagnosed with encephalopathy

(Filatov et al., 2020). The male was a severed alteration in mental status that requires

a neurologist consultant. The diagnosis consisted of an ACT scan of the head, and

EEG of the male. The CT scan showed no acute abnormalities with the presence of

an area of encephalomalacia in the left temporal region of the head. EEG showed

binary deceleration and focal deceleration in the left temporal part of head with sharply

defined waves.

Case 2: Potential acute necrotizing encephalopathy (ANE)

The second case is a female airline worker with COVID-19 diagnosed with ANE

(Desforges et al., 2020). Head tomographs confirmed symmetric hypoattenuation

within the two-medial thalamus with standard CT angiography and CT venogram

tomography.

Electronic copy available at: https://ssrn.com/abstract=3573520

Conclusion

Health care providers should be aware that patients with COVID-19 can have

encephalopathy during hospitalization. This encephalitis should be accompanied by

Page | 5
the detection of SARS-CoV-2 in cerebrospinal fluid by Real-Time Polymerase Chain

Reaction (RT-PCR).

Declaration of Conflicts of Interest

The authors declare no competing interests.

References

Bale, J.F., Jr. Virus and Immune-Mediated Encephalitides: Epidemiology, Diagnosis,

Treatment, and Prevention. Pediatr. Neurol. 2015, 53: 3–12.

Chan, J. F.-W., Yuan, S., Kok, K.-H., To, K. K.-W., Chu, H., Yang, J., Xing, F., Liu, J.,

Yip, C. C.-Y. & Poon, R. W.-S. 'A familial cluster of pneumonia associated with

the 2019 novel coronavirus indicating person-to-person transmission: a study of

a family cluster'. Lancet. 2020, 395 (10223):514-523.

Desforges, M., Le Coupanec, A., Dubeau, P., Bourgouin, A., Lajoie, L., Dubé, M. &

Talbot, P. J. 'Human Coronaviruses and Other Respiratory Viruses:

Underestimated Opportunistic Pathogens of the Central Nervous System?'.

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Desforges, M., Le Coupanec, A., Dubeau, P., Bourgouin, A., Lajoie, L., Dubé, M. &

Talbot, P. J. 'Human Coronaviruses and Other Respiratory Viruses:

Underestimated Opportunistic Pathogens of the Central Nervous System?'.

Viruses. 2020, 12 (1): 14.

Electronic copy available at: https://ssrn.com/abstract=3573520

 Filatov A, Sharma P, Hindi F, et al. Neurological Complications of Coronavirus Disease

(COVID-19): Encephalopathy. Cureus. (March 21, 2020), 12(3): e7352. DOI

10.7759/cureus.7352.
Page | 6
Jebril, Nadia, World Health Organization Declared a Pandemic Public Health Menace:

A Systematic Review of the Coronavirus Disease 2019 “COVID-19”, up to 26th

March 2020 (2020a). Available at SSRN: https://ssrn.com/abstract=3566298

Jebril, Nadia, Distinguishing Epidemiological Curve of Novel Coronavirus Disease

(COVID-19) Cases in Iraq: How It Does not Follow the Epidemic Curve of China

(2020b). Available at SSRN: https://ssrn.com/abstract=3571889 or

http://dx.doi.org/10.2139/ssrn.3571889

Spiegel, M.; Weber, F. Inhibition of cytokine gene expression and induction of

chemokine genes in non-lymphatic cells infected with SARS coronavirus. Virol.

J. 2006, 3, 17.

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