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SARS-CoV-2 infection results in lasting and systemic perturbations post recovery

View ORCID ProfileJustin J. Frere, Randal A. Serafini, Kerri D. Pryce, Marianna Zazhytska, Kohei Oishi, Ilona Golynker, Maryline Panis, Jeffrey Zimering, Shu Horiuchi, Daisy A. Hoagland, Rasmus Møller, Anne Ruiz, Jonathan B. Overdevest, Albana Kodra, Peter D. Canoll, James E. Goldman, Alain C. Borczuk, Vasuretha Chandar, Yaron Bram, Robert Schwartz, Stavros Lomvardas, Venetia Zachariou, Benjamin R. tenOever
doi: https://doi.org/10.1101/2022.01.18.476786
Justin J. Frere
1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY
2Department of Microbiology, New York University, Langone Health, New York, NY
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  • ORCID record for Justin J. Frere
Randal A. Serafini
3Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY
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Kerri D. Pryce
3Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY
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Marianna Zazhytska
4Mortimer B. Zuckerman Mind, Brain and Behavior Institute, Columbia University, New York, NY
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Kohei Oishi
2Department of Microbiology, New York University, Langone Health, New York, NY
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Ilona Golynker
2Department of Microbiology, New York University, Langone Health, New York, NY
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Maryline Panis
2Department of Microbiology, New York University, Langone Health, New York, NY
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Jeffrey Zimering
3Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY
5Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY
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Shu Horiuchi
2Department of Microbiology, New York University, Langone Health, New York, NY
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Daisy A. Hoagland
1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY
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Rasmus Møller
2Department of Microbiology, New York University, Langone Health, New York, NY
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Anne Ruiz
3Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY
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Jonathan B. Overdevest
6Department of Otolaryngology- Head and Neck Surgery, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
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Albana Kodra
4Mortimer B. Zuckerman Mind, Brain and Behavior Institute, Columbia University, New York, NY
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Peter D. Canoll
7Department of Pathology and Cell Biology, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
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James E. Goldman
7Department of Pathology and Cell Biology, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
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Alain C. Borczuk
8Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY
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Vasuretha Chandar
9Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY
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Yaron Bram
9Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY
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Robert Schwartz
9Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY
10Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY
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Stavros Lomvardas
4Mortimer B. Zuckerman Mind, Brain and Behavior Institute, Columbia University, New York, NY
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Venetia Zachariou
3Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY
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  • For correspondence: venetia.zachariou@mssm.edu Benjamin.tenOever@nyulangone.org
Benjamin R. tenOever
1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY
2Department of Microbiology, New York University, Langone Health, New York, NY
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  • For correspondence: venetia.zachariou@mssm.edu Benjamin.tenOever@nyulangone.org
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SUMMARY

SARS-CoV-2 has been found capable of inducing prolonged pathologies collectively referred to as Long-COVID. To better understand this biology, we compared the short- and long-term systemic responses in the golden hamster following either SARS-CoV-2 or influenza A virus (IAV) infection. While SARS-CoV-2 exceeded IAV in its capacity to cause injury to the lung and kidney, the most significant changes were observed in the olfactory bulb (OB) and olfactory epithelium (OE) where inflammation was visible beyond one month post SARS-CoV-2 infection. Despite a lack of detectable virus, OB/OE demonstrated microglial and T cell activation, proinflammatory cytokine production, and interferon responses that correlated with behavioral changes. These findings could be corroborated through sequencing of individuals who recovered from COVID-19, as sustained inflammation in OB/OE tissue remained evident months beyond disease resolution. These data highlight a molecular mechanism for persistent COVID-19 symptomology and characterize a small animal model to develop future therapeutics.

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. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 20, 2022.
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SARS-CoV-2 infection results in lasting and systemic perturbations post recovery
Justin J. Frere, Randal A. Serafini, Kerri D. Pryce, Marianna Zazhytska, Kohei Oishi, Ilona Golynker, Maryline Panis, Jeffrey Zimering, Shu Horiuchi, Daisy A. Hoagland, Rasmus Møller, Anne Ruiz, Jonathan B. Overdevest, Albana Kodra, Peter D. Canoll, James E. Goldman, Alain C. Borczuk, Vasuretha Chandar, Yaron Bram, Robert Schwartz, Stavros Lomvardas, Venetia Zachariou, Benjamin R. tenOever
bioRxiv 2022.01.18.476786; doi: https://doi.org/10.1101/2022.01.18.476786
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SARS-CoV-2 infection results in lasting and systemic perturbations post recovery
Justin J. Frere, Randal A. Serafini, Kerri D. Pryce, Marianna Zazhytska, Kohei Oishi, Ilona Golynker, Maryline Panis, Jeffrey Zimering, Shu Horiuchi, Daisy A. Hoagland, Rasmus Møller, Anne Ruiz, Jonathan B. Overdevest, Albana Kodra, Peter D. Canoll, James E. Goldman, Alain C. Borczuk, Vasuretha Chandar, Yaron Bram, Robert Schwartz, Stavros Lomvardas, Venetia Zachariou, Benjamin R. tenOever
bioRxiv 2022.01.18.476786; doi: https://doi.org/10.1101/2022.01.18.476786

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