Encephalitis associated with the SARS-CoV-2 virus: A case report

Vandervorst, Fenne; Guldolf, Kaat; Peeters, Ilse; Vanderhasselt, Tim; Michiels, Kathleen; Berends, Kinge Johanna; Laethem, Johan Van; Pipeleers, Lissa; Vincken, Stefanie; Seynaeve, Laura; Engelborghs, Sebastiaan

doi:10.1016/j.inat.2020.100821

Cited by 31 publications

(56 citation statements)

References 5 publications

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“…Unlike H5N1 virus infection, SARS-CoV-2 is rarely detected in the CNS of fatal COVID-19 patients or experimentally inoculated animals 11–15 . In addition, only a handful of case reports of SARS-CoV-2 induced encephalitis have been reported 39,40 .. Altogether, these observations are consistent with our findings of poor SARS-CoV-2 replication in hiPSC-derived NPCs, neurons and astrocytes, and supports a pathophysiological model whereby SARS-CoV-2 invades the CNS, but does not replicate efficiently in CNS cell types.…”

Section: Discussionsupporting

confidence: 91%

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Replication kinetic, cell tropism and associated immune responses in SARS-CoV-2 and H5N1 virus infected human iPSC derived neural models

Bauer

Lendemeijer

Leijten

et al. 2021

Preprint

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a wide variety of neurological complications. Even though SARS-CoV-2 is rarely detected in the central nervous system (CNS) or cerebrospinal fluid, evidence is accumulating that SARS-CoV-2 might enter the CNS via the olfactory nerve. However, what happens after SARS-CoV-2 enters the CNS is poorly understood. Therefore, we investigated the replication kinetics, cell tropism, and associated immune responses of SARS-CoV-2 infection in different types of neural cultures derived from human induced pluripotent stem cells (hiPSCs). SARS-CoV-2 was compared to the neurotropic and highly pathogenic H5N1 influenza A virus. SARS-CoV-2 infected a minority of individual mature neurons, without subsequent virus replication and spread, despite ACE2, TMPRSS2 and NPR1 expression in all cultures. However, this sparse infection did result in the production of type-III-interferons and IL-8. In contrast, H5N1 virus replicated and spread very efficiently in all cell types in all cultures. Taken together, our findings support the hypothesis that neurological complications might result from local immune responses triggered by virus invasion, rather than abundant SARS-CoV-2 replication in the CNS.

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Section: Discussionsupporting

confidence: 91%

“…Unlike H5N1 virus infection, SARS-CoV-2 is rarely detected in the CNS of fatal COVID-19 patients or experimentally inoculated animals [11][12][13][14][15] . In addition, only a handful of case reports of SARS-CoV-2 induced encephalitis have been reported 39,40 . .…”

Section: Discussionmentioning

confidence: 99%

Replication kinetic, cell tropism and associated immune responses in SARS-CoV-2 and H5N1 virus infected human iPSC derived neural models

Bauer

Lendemeijer

Leijten

et al. 2021

Preprint

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“…Autoimmune antibodies were tested in the CSF of 72/430 (17%) patients (60 (83%) of whom were encephalopathic or comatose, 4 (6%) of whom were paraparetic, 3 (4%) of whom had seizures, 3 (4%) of whom had cerebellar symptoms, 1 (1%) of whom had parkinsonism and 1 (1%) of whom was locked-in) [ 10 , 25 , 30 , 34 , 44 , 45 , 74 , 122 , 135 , 136 , 141 , 148 , 154 , 164 , 169 , 171 , 177 , 182 , 185 , 186 , 191 , 193 , 194 , [205] , [206] , [207] , 209 , 213 , 215 , 216 , 220 , 233 , 234 , 242 , 245 , 246 ]. Of the 72 patients who had autoimmune antibodies tested in the CSF, 4 (6%) had positive autoimmune antibodies [ 30 , 169 , 171 , 205 ].…”

Section: Resultsmentioning

confidence: 99%

Cerebrospinal fluid in COVID-19: A systematic review of the literature

Lewis

Frontera

Placantonakis

et al. 2021

Journal of the Neurological Sciences

154

152

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We sought to review the literature on cerebrospinal fluid (CSF) testing in patients with COVID-19 for evidence of viral neuroinvasion by SARS-CoV-2. Methods: We performed a systematic review of Medline and Embase between December 1, 2019 and November 18, 2020 to identify case reports or series of patients who had COVID-19 diagnosed based on positive SARS-CoV-2 polymerase chain reaction (PCR) or serologic testing and had CSF testing due to a neurologic symptom. Results: We identified 242 relevant documents which included 430 patients with COVID-19 who had acute neurological symptoms prompting CSF testing. Of those, 321 (75%) patients had symptoms that localized to the central nervous system (CNS). Of 304 patients whose CSF was tested for SARS-CoV-2 PCR, there were 17 (6%) whose test was positive, all of whom had symptoms that localized to the central nervous system (CNS). The majority (13/17, 76%) of these patients were admitted to the hospital because of neurological symptoms. Of 58 patients whose CSF was tested for SARS-CoV-2 antibody, 7 (12%) had positive antibodies with evidence of intrathecal synthesis, all of whom had symptoms that localized to the CNS. Of 132 patients who had oligoclonal bands evaluated, 3 (2%) had evidence of intrathecal antibody synthesis. Of 77 patients tested for autoimmune antibodies in the CSF, 4 (5%) had positive findings. Conclusion: Detection of SARS-CoV-2 in CSF via PCR or evaluation for intrathecal antibody synthesis appears to be rare. Most neurological complications associated with SARS-CoV-2 are unlikely to be related to direct viral neuroinvasion.

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“…The most used pharmacological agents (Table 3) were hyroxychloroquine (48.48%), azithromycin (27.27%), and favipiravir (24.24%). Intravenous steroids were given in 8 cases (5 methylprednisolone 18,26,29,31,32 , 2 dexamethasone 28,33 , 1 unspeci ed 21 ), while immunotherapy such as, plasmapheresis and intravenous immunoglobulin (IVIG) were given to 10 patients (6 plasmapheresis 34 , 4…”

Section: Resultsmentioning

confidence: 99%

COVID-19-Associated Encephalitis: Systematic Review of Case ReportsFindings on Cytokine-Immune-Mediated Inflammation as an Underlying Mechanism

Siahaan¹,

Puspitasari

Pangestu

2020

Preprint

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Background : Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily attacks the respiratory system resulting to a disease called coronavirus disease 19 (COVID-19), several studies also reported the involvement of the central nervous system along the course of the disease, one of which manifest as encephalitis. This study aims to determine the clinical profile, laboratory, and imaging results of encephalitis associated with COVID-19.Methods : Three databases namely, PubMed / Medline, Embase, and Scopus were systematically used in the search for this literature, in order to gather case reports and case series related to COVID-19-associated encephalitis published from January 1, 2019 to July 20, 2020.Result: There were 24 studies with 33 cases included in this review. The most reported neurological symptoms were disorientation / confusion (72.72%), decreased consciousness (54.54%), and seizures (27.27%). The laboratory examination showed an increase in the levels of C-reactive protein (48.48%), lactate dehydrogenase (30.3%), and lymphophenia (27.27%). The brain imaging examination did not show any pathological findings in half of the cases (51.51%). EEG (electroencephalography) showed a generalized decrease in 45.45% of the cases. The CSF analysis showed an increase in the levels of protein (42.42%) and lymphocytosis (24.24%). Positive cerebrospinal fluid polymerase chain reaction (PCR) was only found in 3 cases, while the most widely used pharmacological agent was hyroxychloroquine (48.48%). Intravenous steroids were given in 8 cases, while immunotherapy such as plasmapheresis and intravenous immunoglobulin were given in 10 cases. Fifteen patients were reported to be discharged from the hospital in stable conditions, while four mortality cases were recorded. Conclusion: The clinical, laboratory, and imaging findings in this review supported the hypothesis that the process of cytokine-immune mediated inflammation was the cause of cerebral damage in COVID-19-associated encephalitis, rather than direct invasion. However, due to the limited availabile facilities in this study, further research and examination are needed to confirm the hypothesis

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Encephalitis associated with the SARS-CoV-2 virus: A case report

Cited by 31 publications

References 5 publications

Replication kinetic, cell tropism and associated immune responses in SARS-CoV-2 and H5N1 virus infected human iPSC derived neural models

Replication kinetic, cell tropism and associated immune responses in SARS-CoV-2 and H5N1 virus infected human iPSC derived neural models

Cerebrospinal fluid in COVID-19: A systematic review of the literature

COVID-19-Associated Encephalitis: Systematic Review of Case ReportsFindings on Cytokine-Immune-Mediated Inflammation as an Underlying Mechanism

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