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COVID-19 Neuropathology: evidence for SARS-CoV-2 invasion of Human Brainstem Nuclei

View ORCID ProfileAron Emmi, View ORCID ProfileStefania Rizzo, View ORCID ProfileLuisa Barzon, View ORCID ProfileMichele Sandre, Elisa Carturan, View ORCID ProfileAlessandro Sinigaglia, View ORCID ProfileSilvia Riccetti, Mila della Barbera, View ORCID ProfileRafael Boscolo-Berto, View ORCID ProfilePatrizia Cocco, View ORCID ProfileVeronica Macchi, View ORCID ProfileAngelo Antonini, View ORCID ProfileMonica De Gaspari, View ORCID ProfileCristina Basso, View ORCID ProfileRaffaele De Caro, View ORCID ProfileAndrea Porzionato
doi: https://doi.org/10.1101/2022.06.29.498117
Aron Emmi
1Institute of Human Anatomy, Department of Neuroscience, University of Padova, Italy;
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Stefania Rizzo
2Department of Cardio-Thoracic-Vascular Sciences & Public Health, University of Padova, Italy;
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  • ORCID record for Stefania Rizzo
Luisa Barzon
3Department of Molecular Medicine, University of Padova, Padova, Italy;
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Michele Sandre
4Movement Disorders Unit, Neurology Clinic, Department of Neuroscience, University of Padova;
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Elisa Carturan
2Department of Cardio-Thoracic-Vascular Sciences & Public Health, University of Padova, Italy;
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Alessandro Sinigaglia
3Department of Molecular Medicine, University of Padova, Padova, Italy;
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Silvia Riccetti
3Department of Molecular Medicine, University of Padova, Padova, Italy;
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Mila della Barbera
2Department of Cardio-Thoracic-Vascular Sciences & Public Health, University of Padova, Italy;
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Rafael Boscolo-Berto
1Institute of Human Anatomy, Department of Neuroscience, University of Padova, Italy;
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  • ORCID record for Rafael Boscolo-Berto
Patrizia Cocco
5Pathology and Histopathology Unit, Ospedali Riuniti Padova Sud, Padova, Italy
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  • ORCID record for Patrizia Cocco
Veronica Macchi
1Institute of Human Anatomy, Department of Neuroscience, University of Padova, Italy;
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  • ORCID record for Veronica Macchi
Angelo Antonini
4Movement Disorders Unit, Neurology Clinic, Department of Neuroscience, University of Padova;
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  • ORCID record for Angelo Antonini
Monica De Gaspari
2Department of Cardio-Thoracic-Vascular Sciences & Public Health, University of Padova, Italy;
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Cristina Basso
2Department of Cardio-Thoracic-Vascular Sciences & Public Health, University of Padova, Italy;
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  • ORCID record for Cristina Basso
Raffaele De Caro
1Institute of Human Anatomy, Department of Neuroscience, University of Padova, Italy;
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  • For correspondence: rdecaro@unipd.it
Andrea Porzionato
1Institute of Human Anatomy, Department of Neuroscience, University of Padova, Italy;
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  • ORCID record for Andrea Porzionato
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Abstract

Neurological manifestations are common in COVID-19, the disease caused by SARS-CoV-2. Despite reports of SARS-CoV-2 detection in the brain and cerebrospinal fluid of COVID-19 patients, it’s still unclear whether the virus can infect the central nervous system, and which neuropathological alterations can be ascribed to viral tropism, rather than immune-mediated mechanisms.

Here, we assess neuropathological alterations in 24 COVID-19 patients and 18 matched controls who died due to pneumonia / respiratory failure. Aside from a wide spectrum of neuropathological alterations, SARS-CoV-2-immunoreactive neurons were detected in specific brainstem nuclei of 5 COVID-19 subjects. Viral RNA was also detected by real-time RT-PCR. Quantification of reactive microglia revealed an anatomically segregated pattern of inflammation within affected brainstem regions, and was higher when compared to controls. While the results of this study support the neuroinvasive potential of SARS-CoV-2, the role of SARS-CoV-2 neurotropism in COVID-19 and its long-term sequelae require further investigation.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 05, 2022.
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COVID-19 Neuropathology: evidence for SARS-CoV-2 invasion of Human Brainstem Nuclei
Aron Emmi, Stefania Rizzo, Luisa Barzon, Michele Sandre, Elisa Carturan, Alessandro Sinigaglia, Silvia Riccetti, Mila della Barbera, Rafael Boscolo-Berto, Patrizia Cocco, Veronica Macchi, Angelo Antonini, Monica De Gaspari, Cristina Basso, Raffaele De Caro, Andrea Porzionato
bioRxiv 2022.06.29.498117; doi: https://doi.org/10.1101/2022.06.29.498117
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COVID-19 Neuropathology: evidence for SARS-CoV-2 invasion of Human Brainstem Nuclei
Aron Emmi, Stefania Rizzo, Luisa Barzon, Michele Sandre, Elisa Carturan, Alessandro Sinigaglia, Silvia Riccetti, Mila della Barbera, Rafael Boscolo-Berto, Patrizia Cocco, Veronica Macchi, Angelo Antonini, Monica De Gaspari, Cristina Basso, Raffaele De Caro, Andrea Porzionato
bioRxiv 2022.06.29.498117; doi: https://doi.org/10.1101/2022.06.29.498117

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