TY - JOUR
T1 - COVID-19 induces CNS cytokine expression and loss of hippocampal neurogenesis
AU - Soung, Allison L.
AU - Vanderheiden, Abigail
AU - Nordvig, Anna S.
AU - Sissoko, Cheick A.
AU - Canoll, Peter
AU - Mariani, Madeline B.
AU - Jiang, Xiaoping
AU - Bricker, Traci
AU - Rosoklija, Gorazd B.
AU - Arango, Victoria
AU - Underwood, Mark
AU - Mann, J. John
AU - Dwork, Andrew J.
AU - Goldman, James E.
AU - Boon, Adrianus C.M.
AU - Boldrini, Maura
AU - Klein, Robyn S.
N1 - Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press on behalf of the Guarantors of Brain.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with acute and postacute cognitive and neuropsychiatric symptoms including impaired memory, concentration, attention, sleep and affect. Mechanisms underlying these brain symptoms remain understudied. Here we report that SARS-CoV-2-infected hamsters exhibit a lack of viral neuroinvasion despite aberrant blood-brain barrier permeability. Hamsters and patients deceased from coronavirus disease 2019 (COVID-19) also exhibit microglial activation and expression of interleukin (IL)-1β and IL-6, especially within the hippocampus and the medulla oblongata, when compared with non-COVID control hamsters and humans who died from other infections, cardiovascular disease, uraemia or trauma. In the hippocampal dentate gyrus of both COVID-19 hamsters and humans, we observed fewer neuroblasts and immature neurons. Protracted inflammation, blood-brain barrier disruption and microglia activation may result in altered neurotransmission, neurogenesis and neuronal damage, explaining neuropsychiatric presentations of COVID-19. The involvement of the hippocampus may explain learning, memory and executive dysfunctions in COVID-19 patients.
AB - Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with acute and postacute cognitive and neuropsychiatric symptoms including impaired memory, concentration, attention, sleep and affect. Mechanisms underlying these brain symptoms remain understudied. Here we report that SARS-CoV-2-infected hamsters exhibit a lack of viral neuroinvasion despite aberrant blood-brain barrier permeability. Hamsters and patients deceased from coronavirus disease 2019 (COVID-19) also exhibit microglial activation and expression of interleukin (IL)-1β and IL-6, especially within the hippocampus and the medulla oblongata, when compared with non-COVID control hamsters and humans who died from other infections, cardiovascular disease, uraemia or trauma. In the hippocampal dentate gyrus of both COVID-19 hamsters and humans, we observed fewer neuroblasts and immature neurons. Protracted inflammation, blood-brain barrier disruption and microglia activation may result in altered neurotransmission, neurogenesis and neuronal damage, explaining neuropsychiatric presentations of COVID-19. The involvement of the hippocampus may explain learning, memory and executive dysfunctions in COVID-19 patients.
KW - COVID-19
KW - SARS-CoV-2
KW - brain
KW - cytokine
KW - neurogenesis
UR - http://www.scopus.com/inward/record.url?scp=85139988572&partnerID=8YFLogxK
U2 - 10.1093/brain/awac270
DO - 10.1093/brain/awac270
M3 - Article
C2 - 36004663
AN - SCOPUS:85139988572
SN - 0006-8950
VL - 145
SP - 4193
EP - 4201
JO - Brain
JF - Brain
IS - 12
ER -