Protein Expression Profile of ACE2 in the Normal and COVID-19-Affected Human Brain.

SARS-coronavirus 2 (SARS-CoV-2) that caused the coronavirus disease 2019 (COVID-19) pandemic has posed to be a global challenge. An increasing number of neurological symptoms have been linked to the COVID-19 disease, but the underlying mechanisms of such symptoms and which patients could be at risk are not yet established. The suggested key receptor for host cell entry is angiotensin I converting enzyme 2 (ACE2). Previous studies on limited tissue material have shown no or low protein expression of ACE2 in the normal brain. Here, we used stringently validated antibodies and immunohistochemistry to examine the protein expression of ACE2 in all major regions of the normal brain. The expression pattern was compared with the COVID-19-affected brain of patients with a varying degree of neurological symptoms. In the normal brain, the expression was restricted to the choroid plexus and ependymal cells with no expression in any other brain cell types. Interestingly, in the COVID-19-affected brain, an upregulation of ACE2 was observed in endothelial cells of certain patients, most prominently in the white matter and with the highest expression observed in the patient with the most severe neurological symptoms. The data shows differential expression of ACE2 in the diseased brain and highlights the need to further study the role of endothelial cells in COVID-19 disease in relation to neurological symptoms.

Intracranial Pressure Dynamics and Cerebral Vasomotor Reactivity in Coronavirus Disease 2019 Patient With Acute Encephalitis.

We describe the intracranial pressure dynamics and cerebral vasomotor reactivity in a coronavirus disease 2019 patient with acute encephalitis treated with cerebrospinal fluid drainage and therapeutic plasma exchange. DATA SOURCES: Coronavirus disease ICU, Uppsala University Hospital, Sweden. STUDY SELECTION: Case report. DATA EXTRACTION: Radiology, intracranial pressure, intracranial compliance (correlation between intracranial pressure amplitude and mean intracranial pressure), cerebral vasomotor reactivity (pressure reactivity index), arterial blood pressure, cerebrospinal fluid chemistry, and treatment. DATA SYNTHESIS: None. CONCLUSIONS: This is the first reported case of intracranial pressure monitoring in a patient with acute encephalitis following coronavirus disease 2019. Intracranial pressure data exhibited a high incidence of plateau waves with intracranial pressure insults above 40 mm Hg that required cerebrospinal fluid drainage. Intracranial compliance was low, and pressure reactivity was intact. It is probable that the combination of low intracranial compliance and intact pressure autoregulation explain the high degree of plateau intracranial pressure waves and intracranial pressure variability. This case illustrates that it could be of value to consider intracranial pressure monitoring in selected coronavirus disease 2019 patients with suspicion of increased intracranial pressure to be able to confirm and treat intracranial hypertension if needed. In this patient, therapeutic plasma exchange was safe and efficacious as the level of neuroinflammation decreased and the patient regained consciousness.

Biomarkers for central nervous system injury in cerebrospinal fluid are elevated in COVID-19 and associated with neurological symptoms and disease severity.

BACKGROUND AND PURPOSE: Neurological symptoms have been frequently reported in hospitalized patients with coronavirus disease 2019 (COVID-19), and biomarkers of central nervous system (CNS) injury are reported to be increased in plasma but not extensively studied in cerebrospinal fluid (CSF). This study examined CSF for biomarkers of CNS injury and other pathology in relation to neurological symptoms and disease severity in patients with neurological manifestations of COVID-19. METHODS: Nineteen patients with neurological symptoms and mild to critical COVID-19 were prospectively included. Extensive analysis of CSF, including measurement of biomarkers of CNS injury (neurofilament light chain [NfL] protein, glial fibrillary acidic protein [GFAp], and total tau), was performed and compared to neurological features and disease severity. RESULTS: Neurological symptoms included altered mental status (42%), headache (42%), and central (21%) and peripheral weakness (32%). Two patients demonstrated minor pleocytosis, and four patients had increased immunoglobulin G levels in CSF. Neuronal autoantibody testing using commercial tests was negative in all patients. Increased CSF levels of NfL protein, total tau, and GFAp were seen in 63%, 37%, and 16% of patients, respectively. Increased NfL protein correlated with disease severity, time in intensive care, and level of consciousness. NfL protein in CSF was higher in patients with central neurological symptoms. CONCLUSIONS: Although limited by the small sample size, our data suggest that levels of NfL protein, GFAp, and total tau in CSF are commonly elevated in patients with COVID-19 with neurological symptoms. This is in contrast to the standard CSF workup where pathological findings are scarce. NfL protein, in particular, is associated with central neurological symptoms and disease severity.

Intracranial Pressure Dynamics and Cerebral Vasomotor Reactivity in Coronavirus Disease 2019 Patient With Acute Encephalitis.

We describe the intracranial pressure dynamics and cerebral vasomotor reactivity in a coronavirus disease 2019 patient with acute encephalitis treated with cerebrospinal fluid drainage and therapeutic plasma exchange. DATA SOURCES: Coronavirus disease ICU, Uppsala University Hospital, Sweden. STUDY SELECTION: Case report. DATA EXTRACTION: Radiology, intracranial pressure, intracranial compliance (correlation between intracranial pressure amplitude and mean intracranial pressure), cerebral vasomotor reactivity (pressure reactivity index), arterial blood pressure, cerebrospinal fluid chemistry, and treatment. DATA SYNTHESIS: None. CONCLUSIONS: This is the first reported case of intracranial pressure monitoring in a patient with acute encephalitis following coronavirus disease 2019. Intracranial pressure data exhibited a high incidence of plateau waves with intracranial pressure insults above 40 mm Hg that required cerebrospinal fluid drainage. Intracranial compliance was low, and pressure reactivity was intact. It is probable that the combination of low intracranial compliance and intact pressure autoregulation explain the high degree of plateau intracranial pressure waves and intracranial pressure variability. This case illustrates that it could be of value to consider intracranial pressure monitoring in selected coronavirus disease 2019 patients with suspicion of increased intracranial pressure to be able to confirm and treat intracranial hypertension if needed. In this patient, therapeutic plasma exchange was safe and efficacious as the level of neuroinflammation decreased and the patient regained consciousness.