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2.
Nature ; 595(7868): 565-571, 2021 07.
Article in English | MEDLINE | ID: covidwho-1275939

ABSTRACT

Although SARS-CoV-2 primarily targets the respiratory system, patients with and survivors of COVID-19 can suffer neurological symptoms1-3. However, an unbiased understanding of the cellular and molecular processes that are affected in the brains of patients with COVID-19 is missing. Here we profile 65,309 single-nucleus transcriptomes from 30 frontal cortex and choroid plexus samples across 14 control individuals (including 1 patient with terminal influenza) and 8 patients with COVID-19. Although our systematic analysis yields no molecular traces of SARS-CoV-2 in the brain, we observe broad cellular perturbations indicating that barrier cells of the choroid plexus sense and relay peripheral inflammation into the brain and show that peripheral T cells infiltrate the parenchyma. We discover microglia and astrocyte subpopulations associated with COVID-19 that share features with pathological cell states that have previously been reported in human neurodegenerative disease4-6. Synaptic signalling of upper-layer excitatory neurons-which are evolutionarily expanded in humans7 and linked to cognitive function8-is preferentially affected in COVID-19. Across cell types, perturbations associated with COVID-19 overlap with those found in chronic brain disorders and reside in genetic variants associated with cognition, schizophrenia and depression. Our findings and public dataset provide a molecular framework to understand current observations of COVID-19-related neurological disease, and any such disease that may emerge at a later date.


Subject(s)
Astrocytes/pathology , Brain/pathology , COVID-19/diagnosis , COVID-19/pathology , Choroid Plexus/pathology , Microglia/pathology , Neurons/pathology , Aged , Aged, 80 and over , Brain/metabolism , Brain/physiopathology , Brain/virology , COVID-19/genetics , COVID-19/physiopathology , Cell Nucleus/genetics , Choroid Plexus/metabolism , Choroid Plexus/physiopathology , Choroid Plexus/virology , Female , Humans , Inflammation/virology , Male , Middle Aged , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity , Single-Cell Analysis , Transcriptome , Virus Replication
3.
Nat Neurosci ; 24(2): 168-175, 2021 02.
Article in English | MEDLINE | ID: covidwho-1060446

ABSTRACT

The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease. Moreover, thromboembolic events throughout the body, including in the CNS, have been described. Given the neurological symptoms observed in a large majority of individuals with COVID-19, SARS-CoV-2 penetrance of the CNS is likely. By various means, we demonstrate the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain. Furthermore, we describe the morphological changes associated with infection such as thromboembolic ischemic infarction of the CNS and present evidence of SARS-CoV-2 neurotropism. SARS-CoV-2 can enter the nervous system by crossing the neural-mucosal interface in olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue, including delicate olfactory and sensory nerve endings. Subsequently, SARS-CoV-2 appears to follow neuroanatomical structures, penetrating defined neuroanatomical areas including the primary respiratory and cardiovascular control center in the medulla oblongata.


Subject(s)
Brain/virology , COVID-19/virology , Olfactory Mucosa/virology , SARS-CoV-2/pathogenicity , Central Nervous System , Humans , RNA, Viral/genetics , Smell/physiology , Virus Internalization
4.
Nat Neurosci ; 24(2): 168-175, 2021 02.
Article in English | MEDLINE | ID: covidwho-952133

ABSTRACT

The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease. Moreover, thromboembolic events throughout the body, including in the CNS, have been described. Given the neurological symptoms observed in a large majority of individuals with COVID-19, SARS-CoV-2 penetrance of the CNS is likely. By various means, we demonstrate the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain. Furthermore, we describe the morphological changes associated with infection such as thromboembolic ischemic infarction of the CNS and present evidence of SARS-CoV-2 neurotropism. SARS-CoV-2 can enter the nervous system by crossing the neural-mucosal interface in olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue, including delicate olfactory and sensory nerve endings. Subsequently, SARS-CoV-2 appears to follow neuroanatomical structures, penetrating defined neuroanatomical areas including the primary respiratory and cardiovascular control center in the medulla oblongata.


Subject(s)
Brain/virology , COVID-19/virology , Olfactory Mucosa/virology , SARS-CoV-2/pathogenicity , Central Nervous System , Humans , RNA, Viral/genetics , Smell/physiology , Virus Internalization
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