PMC:7253233 / 10598-14620 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7253233","sourcedb":"PMC","sourceid":"7253233","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7253233","text":"Discussion\nThe SARS-Coronavirus-2 belongs to the β-coronavirus group which includes several human pathogenic viruses including middle east respiratory syndrome (MERS) coronavirus and SARS-CoV-1. These group of coronaviruses are associated with respiratory symptoms. Additional neurological symptoms including delirium, dizziness, and headaches have also been reported with other coronavirus infections prior to the SARS-CoV-2 outbreak [4]. The case series of patients from Wuhan, China, with COVID-19 disease, included both central and peripheral neurological manifestations (i.e., headache, dizziness, impaired consciousness, cerebrovascular disease, and neuralgia) [2]. Seizures were not reported as a direct manifestation of SARS-CoV-2 infection. The patients described in our series developed focal seizures and, in the second case, even progressed to non-convulsive status epilepticus. Seizures may be a CNS manifestation of COVID-19 disease. Further investigations are needed to elucidate the mechanism of neurological symptoms in SARS-CoV-2 infection.\nHuman coronaviruses (HCoV) have been established to infect human astrocytes and microglia in neural cell cultures as well as detection of viral RNA in a study of human brain autopsy samples supporting their neurotropic and neuroinvasive properties [5]. A case report of SARS-CoV-1 infection with CNS symptoms during the SARS epidemic also isolated the virus within a brain tissue specimen [6]. Although direct evidence of a neurotropic effect of SARS-Cov-2 has not been reported as yet through either cerebrospinal fluid (CSF) or autopsy studies, the presence of neurological symptoms in patients with COVID-19 disease during this current pandemic, and the similarity between the two strains of human coronaviruses (CoV-1 and CoV-2), makes this mechanism highly suggestive. Acute symptomatic seizures may be the result of a possible neurotropic effect of the virus or can be a marker of severity of systemic disease itself since CNS symptoms were found mainly in patients with severe COVID-19 disease. After penetration of the blood–brain barrier, the virus can slow the cerebral microcirculation, possibly through the creation of a hypercoagulable state. This allows increased interaction of SARS-CoV-2 with the endothelial receptors and receptors on glial tissue [7]. The interaction at the glia may predispose patients to seizures as seen in other neurological diseases [8, 9].\nPrevious studies of SARS-coronaviruses have described the proliferation of pro-inflammatory cytokines that are active in promoting blood–barrier breakdown, namely interleukin-8 (IL8) and monocyte chemoattractant protein-1 (MCP1) [10, 11]. A description of coronavirus infections in a Japanese encephalitis mouse model demonstrated CNS viral infection induced astrocyte and microglia proliferation, leading to increased release of IL-8 in the CSF [10]. MCP1 is another pro-inflammatory mediator that is expressed in CNS cells including astrocytes, neurons, and microglia. MCP1 may be up-regulated in conditions which target and degrade the blood–brain barrier and can recruit additional inflammatory cells as the monocytes migrate across the blood–brain barrier [11]. We hypothesize that as a result of the accumulation of inflammatory markers, there may be local cortical irritation that precipitates seizures related to COVID-19 infection. Although cerebrospinal fluid may contain markers of inflammation, the treatment of this infection is largely supportive, and with the additional risk of coagulopathy precipitated by SARS-CoV-2, a lumbar puncture may not be justifiable unless there is an alternative diagnosis to be sought. A limitation of our case series is that cerebrospinal fluid was unable to be obtained due to patient factors that made a lumbar puncture relatively contraindicated and that a CSF-PCR test for SARS-CoV-2 was not yet commercially available. As this disease continues to spread, we will continue to learn about its direct and/or indirect 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