SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations after 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; Albana Kodra; Jonathan B. Overdevest; Peter D. Canoll; Alain C. Borczuk; Vasuretha Chandar; Yaron Bram; Robert Schwartz; Stavros Lomvardas; Venetia Zachariou; Benjamin R. tenOever

doi:10.1126/scitranslmed.abq3059

SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations after 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, Albana Kodra, Jonathan B. Overdevest, Peter D. Canoll, Alain C. Borczuk, Vasuretha Chandar, Yaron Bram, Robert Schwartz, Stavros LomvardasVenetia Zachariou, Benjamin R. tenOever

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158 Scopus citations

Abstract

The host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in prolonged pathologies collectively referred to as post-acute sequalae of COVID-19 (PASC) or long COVID. To better understand the mechanism underlying long COVID biology, we compared the short- and long-term systemic responses in the golden hamster after either SARS-CoV-2 or influenza A virus (IAV) infection. Results demonstrated that SARS-CoV-2 exceeded IAV in its capacity to cause permanent injury to the lung and kidney and uniquely affected the olfactory bulb (OB) and olfactory epithelium (OE). Despite a lack of detectable infectious virus, the OB and OE demonstrated myeloid and T cell activation, proinflammatory cytokine production, and an interferon response that correlated with behavioral changes extending a month after viral clearance. These sustained transcriptional changes could also be corroborated from tissue isolated from individuals who recovered from COVID-19. These data highlight a molecular mechanism for persistent COVID-19 symptomology and provide a small animal model to explore future therapeutics.

Original language	English
Article number	abq3059
Journal	Science Translational Medicine
Volume	14
Issue number	664
DOIs	https://doi.org/10.1126/scitranslmed.abq3059
State	Published - 28 Sep 2022

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Frere, J. J., Serafini, R. A., Pryce, K. D., Zazhytska, M., Oishi, K., Golynker, I., Panis, M., Zimering, J., Horiuchi, S., Hoagland, D. A., Møller, R., Ruiz, A., Kodra, A., Overdevest, J. B., Canoll, P. D., Borczuk, A. C., Chandar, V., Bram, Y., Schwartz, R., ... tenOever, B. R. (2022). SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations after recovery. Science Translational Medicine, 14(664), Article abq3059. https://doi.org/10.1126/scitranslmed.abq3059

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title = "SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations after recovery",

abstract = "The host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in prolonged pathologies collectively referred to as post-acute sequalae of COVID-19 (PASC) or long COVID. To better understand the mechanism underlying long COVID biology, we compared the short- and long-term systemic responses in the golden hamster after either SARS-CoV-2 or influenza A virus (IAV) infection. Results demonstrated that SARS-CoV-2 exceeded IAV in its capacity to cause permanent injury to the lung and kidney and uniquely affected the olfactory bulb (OB) and olfactory epithelium (OE). Despite a lack of detectable infectious virus, the OB and OE demonstrated myeloid and T cell activation, proinflammatory cytokine production, and an interferon response that correlated with behavioral changes extending a month after viral clearance. These sustained transcriptional changes could also be corroborated from tissue isolated from individuals who recovered from COVID-19. These data highlight a molecular mechanism for persistent COVID-19 symptomology and provide a small animal model to explore future therapeutics.",

author = "Frere, {Justin J.} and Serafini, {Randal A.} and Pryce, {Kerri D.} and Marianna Zazhytska and Kohei Oishi and Ilona Golynker and Maryline Panis and Jeffrey Zimering and Shu Horiuchi and Hoagland, {Daisy A.} and Rasmus M{\o}ller and Anne Ruiz and Albana Kodra and Overdevest, {Jonathan B.} and Canoll, {Peter D.} and Borczuk, {Alain C.} and Vasuretha Chandar and Yaron Bram and Robert Schwartz and Stavros Lomvardas and Venetia Zachariou and tenOever, {Benjamin R.}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors.",

year = "2022",

month = sep,

day = "28",

doi = "10.1126/scitranslmed.abq3059",

language = "English",

volume = "14",

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Frere, JJ, Serafini, RA, Pryce, KD, Zazhytska, M, Oishi, K, Golynker, I, Panis, M, Zimering, J, Horiuchi, S, Hoagland, DA, Møller, R, Ruiz, A, Kodra, A, Overdevest, JB, Canoll, PD, Borczuk, AC, Chandar, V, Bram, Y, Schwartz, R, Lomvardas, S, Zachariou, V & tenOever, BR 2022, 'SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations after recovery', Science Translational Medicine, vol. 14, no. 664, abq3059. https://doi.org/10.1126/scitranslmed.abq3059

TY - JOUR

T1 - SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations after recovery

AU - Frere, Justin J.

AU - Serafini, Randal A.

AU - Pryce, Kerri D.

AU - Zazhytska, Marianna

AU - Oishi, Kohei

AU - Golynker, Ilona

AU - Panis, Maryline

AU - Zimering, Jeffrey

AU - Horiuchi, Shu

AU - Hoagland, Daisy A.

AU - Møller, Rasmus

AU - Ruiz, Anne

AU - Kodra, Albana

AU - Overdevest, Jonathan B.

AU - Canoll, Peter D.

AU - Borczuk, Alain C.

AU - Chandar, Vasuretha

AU - Bram, Yaron

AU - Schwartz, Robert

AU - Lomvardas, Stavros

AU - Zachariou, Venetia

AU - tenOever, Benjamin R.

PY - 2022/9/28

Y1 - 2022/9/28

N2 - The host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in prolonged pathologies collectively referred to as post-acute sequalae of COVID-19 (PASC) or long COVID. To better understand the mechanism underlying long COVID biology, we compared the short- and long-term systemic responses in the golden hamster after either SARS-CoV-2 or influenza A virus (IAV) infection. Results demonstrated that SARS-CoV-2 exceeded IAV in its capacity to cause permanent injury to the lung and kidney and uniquely affected the olfactory bulb (OB) and olfactory epithelium (OE). Despite a lack of detectable infectious virus, the OB and OE demonstrated myeloid and T cell activation, proinflammatory cytokine production, and an interferon response that correlated with behavioral changes extending a month after viral clearance. These sustained transcriptional changes could also be corroborated from tissue isolated from individuals who recovered from COVID-19. These data highlight a molecular mechanism for persistent COVID-19 symptomology and provide a small animal model to explore future therapeutics.

AB - The host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in prolonged pathologies collectively referred to as post-acute sequalae of COVID-19 (PASC) or long COVID. To better understand the mechanism underlying long COVID biology, we compared the short- and long-term systemic responses in the golden hamster after either SARS-CoV-2 or influenza A virus (IAV) infection. Results demonstrated that SARS-CoV-2 exceeded IAV in its capacity to cause permanent injury to the lung and kidney and uniquely affected the olfactory bulb (OB) and olfactory epithelium (OE). Despite a lack of detectable infectious virus, the OB and OE demonstrated myeloid and T cell activation, proinflammatory cytokine production, and an interferon response that correlated with behavioral changes extending a month after viral clearance. These sustained transcriptional changes could also be corroborated from tissue isolated from individuals who recovered from COVID-19. These data highlight a molecular mechanism for persistent COVID-19 symptomology and provide a small animal model to explore future therapeutics.

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U2 - 10.1126/scitranslmed.abq3059

DO - 10.1126/scitranslmed.abq3059

M3 - Article

C2 - 35857629

AN - SCOPUS:85131804671

SN - 1946-6234

VL - 14

JO - Science Translational Medicine

JF - Science Translational Medicine

IS - 664

M1 - abq3059

ER -

SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations after recovery

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