Brain Inflammation and Intracellular α-Synuclein Aggregates in Macaques after SARS-CoV-2 Infection

ingrid philippens; Kinga Böszörményi; Jacqueline A. M. Wubben; Zahra C. Fagrouch; Nikki van Driel; Amber Mayenburg; Diana Lozovagia; Eva Roos; Bernadette Schurink; Marianna Bugiani; R.E. Bontrop; null Jinte; Willy Bogers; Lioe-Fee de Geus-Oei; Jan Langermans; Ernst Verschoor; Marieke Stammes; Babs E Verstrepen

doi:10.3390/v14040776

Brain Inflammation and Intracellular α-Synuclein Aggregates in Macaques after SARS-CoV-2 Infection

ingrid philippens, Kinga Böszörményi, Jacqueline A. M. Wubben, Zahra C. Fagrouch, Nikki van Driel, Amber Mayenburg, Diana Lozovagia, Eva Roos, Bernadette Schurink, Marianna Bugiani, R.E. Bontrop, Jinte, Willy Bogers, Lioe-Fee de Geus-Oei, Jan Langermans, Ernst Verschoor, Marieke Stammes, Babs E Verstrepen

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

SARS-CoV-2 causes acute respiratory disease, but many patients also experience neurological complications. Neuropathological changes with pronounced neuroinflammation have been described in individuals after lethal COVID-19, as well as in the CSF of hospitalized patients with neurological complications. To assess whether neuropathological changes can occur after a SARS-CoV-2 infection, leading to mild-to-moderate disease, we investigated the brains of four rhesus and four cynomolgus macaques after pulmonary disease and without overt clinical symptoms. Post-mortem analysis demonstrated the infiltration of T-cells and activated microglia in the parenchyma of all infected animals, even in the absence of viral antigen or RNA. Moreover, intracellular α-synu-clein aggregates were found in the brains of both macaque species. The heterogeneity of these manifestations in the brains indicates the virus’ neuropathological potential and should be considered a warning for long-term health risks, following SARS-CoV-2 infection.

Original language	English
Article number	776
Pages (from-to)	1-15
Journal	Viruses
Volume	14
Issue number	4
DOIs	https://doi.org/10.3390/v14040776
Publication status	Published - Apr 2022

Keywords

COVID-19
SARS-CoV-2
macaques
neuroinflammation
positron emission tomography-computed tomography
α-synuclein

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philippens, I., Böszörményi, K., Wubben, J. A. M., Fagrouch, Z. C., Driel, N. V., Mayenburg, A., Lozovagia, D., Roos, E., Schurink, B., Bugiani, M., Bontrop, R. E., Jinte, Bogers, W., Geus-Oei, L.-F. D., Langermans, J., Verschoor, E., Stammes, M., & Verstrepen, B. E. (2022). Brain Inflammation and Intracellular α-Synuclein Aggregates in Macaques after SARS-CoV-2 Infection. Viruses, 14(4), 1-15. Article 776. https://doi.org/10.3390/v14040776

@article{658a393673d34e57bb94168a6d320e7b,

title = "Brain Inflammation and Intracellular α-Synuclein Aggregates in Macaques after SARS-CoV-2 Infection",

abstract = "SARS-CoV-2 causes acute respiratory disease, but many patients also experience neurological complications. Neuropathological changes with pronounced neuroinflammation have been described in individuals after lethal COVID-19, as well as in the CSF of hospitalized patients with neurological complications. To assess whether neuropathological changes can occur after a SARS-CoV-2 infection, leading to mild-to-moderate disease, we investigated the brains of four rhesus and four cynomolgus macaques after pulmonary disease and without overt clinical symptoms. Post-mortem analysis demonstrated the infiltration of T-cells and activated microglia in the parenchyma of all infected animals, even in the absence of viral antigen or RNA. Moreover, intracellular α-synu-clein aggregates were found in the brains of both macaque species. The heterogeneity of these manifestations in the brains indicates the virus{\textquoteright} neuropathological potential and should be considered a warning for long-term health risks, following SARS-CoV-2 infection.",

keywords = "COVID-19, SARS-CoV-2, macaques, neuroinflammation, positron emission tomography-computed tomography, α-synuclein",

author = "ingrid philippens and Kinga B{\"o}sz{\"o}rm{\'e}nyi and Wubben, {Jacqueline A. M.} and Fagrouch, {Zahra C.} and Driel, {Nikki van} and Amber Mayenburg and Diana Lozovagia and Eva Roos and Bernadette Schurink and Marianna Bugiani and R.E. Bontrop and Jinte and Willy Bogers and Geus-Oei, {Lioe-Fee de} and Jan Langermans and Ernst Verschoor and Marieke Stammes and Verstrepen, {Babs E}",

note = "Funding Information: Funding: This study was supported by funding from the Biomedical Primate Research Centre. K.P.B. was supported by the European Union{\textquoteright}s Marie Sk{\l}odowska-Curie Innovative Training Network HONOURs, grant agreement no. 721367. This publication was also supported by the European Virus Archive GLOBAL (EVA-GLOBAL) project, which has received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation programme, under grant agreement no. 871029. Funding Information: This study was supported by funding from the Biomedical Primate Research Centre. K.P.B. was supported by the European Union?s Marie Sk?odowska-Curie Innovative Training Net-work HONOURs, grant agreement no. 721367. This publication was also supported by the European Virus Archive GLOBAL (EVA-GLOBAL) project, which has received funding from the European Union?s Horizon 2020 research and innovation programme, under grant agreement no. 871029. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = apr,

doi = "10.3390/v14040776",

language = "English",

volume = "14",

pages = "1--15",

journal = "Viruses",

issn = "1999-4915",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "4",

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philippens, I, Böszörményi, K, Wubben, JAM, Fagrouch, ZC, Driel, NV, Mayenburg, A, Lozovagia, D, Roos, E, Schurink, B, Bugiani, M, Bontrop, RE, Jinte, Bogers, W, Geus-Oei, L-FD, Langermans, J, Verschoor, E, Stammes, M & Verstrepen, BE 2022, 'Brain Inflammation and Intracellular α-Synuclein Aggregates in Macaques after SARS-CoV-2 Infection', Viruses, vol. 14, no. 4, 776, pp. 1-15. https://doi.org/10.3390/v14040776

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T1 - Brain Inflammation and Intracellular α-Synuclein Aggregates in Macaques after SARS-CoV-2 Infection

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AU - Böszörményi, Kinga

AU - Wubben, Jacqueline A. M.

AU - Fagrouch, Zahra C.

AU - Driel, Nikki van

AU - Mayenburg, Amber

AU - Lozovagia, Diana

AU - Roos, Eva

AU - Schurink, Bernadette

AU - Bugiani, Marianna

AU - Bontrop, R.E.

AU - Jinte, null

AU - Bogers, Willy

AU - Geus-Oei, Lioe-Fee de

AU - Langermans, Jan

AU - Verschoor, Ernst

AU - Stammes, Marieke

AU - Verstrepen, Babs E

N1 - Funding Information: Funding: This study was supported by funding from the Biomedical Primate Research Centre. K.P.B. was supported by the European Union’s Marie Skłodowska-Curie Innovative Training Network HONOURs, grant agreement no. 721367. This publication was also supported by the European Virus Archive GLOBAL (EVA-GLOBAL) project, which has received funding from the European Union’s Horizon 2020 research and innovation programme, under grant agreement no. 871029. Funding Information: This study was supported by funding from the Biomedical Primate Research Centre. K.P.B. was supported by the European Union?s Marie Sk?odowska-Curie Innovative Training Net-work HONOURs, grant agreement no. 721367. This publication was also supported by the European Virus Archive GLOBAL (EVA-GLOBAL) project, which has received funding from the European Union?s Horizon 2020 research and innovation programme, under grant agreement no. 871029. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/4

Y1 - 2022/4

N2 - SARS-CoV-2 causes acute respiratory disease, but many patients also experience neurological complications. Neuropathological changes with pronounced neuroinflammation have been described in individuals after lethal COVID-19, as well as in the CSF of hospitalized patients with neurological complications. To assess whether neuropathological changes can occur after a SARS-CoV-2 infection, leading to mild-to-moderate disease, we investigated the brains of four rhesus and four cynomolgus macaques after pulmonary disease and without overt clinical symptoms. Post-mortem analysis demonstrated the infiltration of T-cells and activated microglia in the parenchyma of all infected animals, even in the absence of viral antigen or RNA. Moreover, intracellular α-synu-clein aggregates were found in the brains of both macaque species. The heterogeneity of these manifestations in the brains indicates the virus’ neuropathological potential and should be considered a warning for long-term health risks, following SARS-CoV-2 infection.

AB - SARS-CoV-2 causes acute respiratory disease, but many patients also experience neurological complications. Neuropathological changes with pronounced neuroinflammation have been described in individuals after lethal COVID-19, as well as in the CSF of hospitalized patients with neurological complications. To assess whether neuropathological changes can occur after a SARS-CoV-2 infection, leading to mild-to-moderate disease, we investigated the brains of four rhesus and four cynomolgus macaques after pulmonary disease and without overt clinical symptoms. Post-mortem analysis demonstrated the infiltration of T-cells and activated microglia in the parenchyma of all infected animals, even in the absence of viral antigen or RNA. Moreover, intracellular α-synu-clein aggregates were found in the brains of both macaque species. The heterogeneity of these manifestations in the brains indicates the virus’ neuropathological potential and should be considered a warning for long-term health risks, following SARS-CoV-2 infection.

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KW - SARS-CoV-2

KW - macaques

KW - neuroinflammation

KW - positron emission tomography-computed tomography

KW - α-synuclein

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U2 - 10.3390/v14040776

DO - 10.3390/v14040776

M3 - Article

C2 - 35458506

SN - 1999-4915

VL - 14

SP - 1

EP - 15

JO - Viruses

JF - Viruses

IS - 4

M1 - 776

ER -

Brain Inflammation and Intracellular α-Synuclein Aggregates in Macaques after SARS-CoV-2 Infection

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Keywords

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