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

Ingrid H. C. H. M. Philippens (‡), Kinga P. Böszörményi (‡), Jacqueline A. M. Wubben, Zahra C. Fagrouch, Nikki van Driel, Amber Q. Mayenburg, Diana Lozovagia, Eva Roos, Bernadette Schurink, Marianna Bugiani, Ronald E. Bontrop, Jinte Middeldorp, Willy M. Bogers, Lioe-Fee de Geus-Oei, Jan A. M. Langermans, Ernst J. Verschoor(§), Marieke A. Stammes(§), Babs E. Verstrepen(§)

‡ / § These authors contributed equally to this work

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. Postmortem 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 _-synuclein 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

Printed April 2022 in Viruses

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HONOURs

Host switching pathogens, infectious outbreaks and zoonosis; a Marie Sklodowska-Curie Innovative Training Network.

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 721367.