Abstract
Original language | English |
---|---|
Article number | 104101 |
Journal | iScience |
Volume | 25 |
Issue number | 4 |
DOIs | |
Publication status | Published - 15 Apr 2022 |
Keywords
- Medical imaging
- Medical microbiology
- Virology
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In: iScience, Vol. 25, No. 4, 104101, 15.04.2022.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Computed tomography and [18F]-FDG PET imaging provide additional readouts for COVID-19 pathogenesis and therapies evaluation in non-human primates
AU - Naninck, Thibaut
AU - Kahlaoui, Nidhal
AU - Lemaitre, Julien
AU - Maisonnasse, Pauline
AU - de Mori, Antoine
AU - Pascal, Quentin
AU - Contreras, Vanessa
AU - Marlin, Romain
AU - Relouzat, Francis
AU - Delache, Benoît
AU - Hérate, C. cile
AU - Aldon, Yoann
AU - van Gils, Marit
AU - Zabaleta, Nerea
AU - Ho Tsong Fang, Raphaël
AU - Bosquet, Nathalie
AU - Sanders, Rogier W.
AU - Vandenberghe, Luk H.
AU - Chapon, Catherine
AU - le Grand, Roger
N1 - Funding Information: We thank E. Burban, J. Demilly, N. Dhooge, S. Langlois, P. Le Calvez, Q. Sconosciuti, V. Magneron, M. Rimlinger, A. Berriche, J.H. Qiu, M. Potier, J. M. Robert, and C. Dodan for help with the animal studies; L. Bossevot, M. Leonec, L. Moenne-Loccoz, and J. Morin for the RT-qPCR, B. Fert and C. Mayet for help with in vivo imaging studies; C. Aubenque, M. Barendji, L. Bossevot, N. Dimant, J. Dinh, A. S. Gallouet, M. Leonec, I. Mangeot, and K. Storck for help with sample processing; M. Albert, M. Barbet, and F. Donati for help with the production, titration, and sequencing of the virus stocks used in vivo; A. S. Gallouet, S. Keyser, E. Marcos-Lopez, B. Targat, and B. Vaslin for help with the experimental studies in the context of COVID-19-induced constraints; F. Ducancel and Y. Gorin for help with the logistics and safety management; the Fondation Bettencourt Schueller and the Region Ile-de-France for their contribution to the implementation of the imaging facilities; and the Domaine d'Intérêt Majeur (DIM) “One Health” for its support. This study received financial support from REACTing, the Fondation pour la Recherche Médicale (ANR; AM-CoV-Path), and the European Union's Horizon 2020 (H2020) research and innovation program Fight-nCov (101003555), European Union IMI2 program CARE (101005077) and the European Infrastructure TRANSVAC2 (730964). We acknowledge support from the Bill and Melinda Gates Foundation. The virus stock was obtained through the EVAg platform (https://www.european-virus-archive.com/), funded by H2020 (653316). The Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure is supported by the “Program Investissements d'Avenir,” managed by the ANR under reference ANR-11-INBS-0008. All data generated or analyzed during this study are available from the corresponding author on reasonable request. Each author contributed significantly to this work. They all have read, revised, and approved the article. There is no conflict of interest. Regarding authors specific contributions, R.L.G. T.N. P.M. L.H.V. and S.W.S. worked on project conception, V.C. R.M. C.H. Y.A. M.V.G. N.Z. R.H.T.F. N.B. and C.C. elaborated the diverse parts of experimental designs, T.N. N.K. F.R. and B.D. acquired the data, T.N. N.K, J.L. P.M. A.D.M. Q.P. V.C. R.M. and C.H. analyzed the data. Regarding article-specific contributions T.N. and N.K. wrote the initial draft and then R.L.G. C.C. J.L. and P.M. critically contributed to the writing. No potential conflicts of interest relevant to this article exist. Funding Information: We thank E. Burban, J. Demilly, N. Dhooge, S. Langlois, P. Le Calvez, Q. Sconosciuti, V. Magneron, M. Rimlinger, A. Berriche, J.H. Qiu, M. Potier, J. M. Robert, and C. Dodan for help with the animal studies; L. Bossevot, M. Leonec, L. Moenne-Loccoz, and J. Morin for the RT-qPCR, B. Fert and C. Mayet for help with in vivo imaging studies; C. Aubenque, M. Barendji, L. Bossevot, N. Dimant, J. Dinh, A. S. Gallouet, M. Leonec, I. Mangeot, and K. Storck for help with sample processing; M. Albert, M. Barbet, and F. Donati for help with the production, titration, and sequencing of the virus stocks used in vivo; A. S. Gallouet, S. Keyser, E. Marcos-Lopez, B. Targat, and B. Vaslin for help with the experimental studies in the context of COVID-19-induced constraints; F. Ducancel and Y. Gorin for help with the logistics and safety management; the Fondation Bettencourt Schueller and the Region Ile-de-France for their contribution to the implementation of the imaging facilities; and the Domaine d’Intérêt Majeur (DIM) “One Health” for its support. This study received financial support from REACTing , the Fondation pour la Recherche Médicale (ANR; AM-CoV-Path), and the European Union’s Horizon 2020 (H2020) research and innovation program Fight-nCov ( 101003555 ), European Union IMI2 program CARE ( 101005077 ) and the European Infrastructure TRANSVAC2 ( 730964 ). We acknowledge support from the Bill and Melinda Gates Foundation . The virus stock was obtained through the EVAg platform ( https://www.european-virus-archive.com/ ), funded by H2020 (653316). The Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure is supported by the “Program Investissements d’Avenir,” managed by the ANR under reference ANR-11-INBS-0008 . All data generated or analyzed during this study are available from the corresponding author on reasonable request. Publisher Copyright: © 2022 The Author(s)
PY - 2022/4/15
Y1 - 2022/4/15
N2 - Non-human primates (NHPs) are particularly relevant as preclinical models for SARS-CoV-2 infection and nuclear imaging may represent a valuable tool for monitoring infection in this species. We investigated the benefit of computed X-ray tomography (CT) and [18F]-FDG positron emission tomography (PET) to monitor the early phase of the disease in a large cohort (n = 76) of SARS-CoV-2 infected macaques. Following infection, animals showed mild COVID-19 symptoms including typical lung lesions. CT scores at the acute phase reflect the heterogeneity of lung burden following infection. Moreover, [18F]-FDG PET revealed that FDG uptake was significantly higher in the lungs, nasal cavities, lung-draining lymph nodes, and spleen of NHPs by 5 days postinfection compared to pre-infection levels, indicating early local inflammation. The comparison of CT and PET data from previous COVID-19 treatments or vaccines we tested in NHP, to this large cohort of untreated animals demonstrated the value of in vivo imaging in preclinical trials.
AB - Non-human primates (NHPs) are particularly relevant as preclinical models for SARS-CoV-2 infection and nuclear imaging may represent a valuable tool for monitoring infection in this species. We investigated the benefit of computed X-ray tomography (CT) and [18F]-FDG positron emission tomography (PET) to monitor the early phase of the disease in a large cohort (n = 76) of SARS-CoV-2 infected macaques. Following infection, animals showed mild COVID-19 symptoms including typical lung lesions. CT scores at the acute phase reflect the heterogeneity of lung burden following infection. Moreover, [18F]-FDG PET revealed that FDG uptake was significantly higher in the lungs, nasal cavities, lung-draining lymph nodes, and spleen of NHPs by 5 days postinfection compared to pre-infection levels, indicating early local inflammation. The comparison of CT and PET data from previous COVID-19 treatments or vaccines we tested in NHP, to this large cohort of untreated animals demonstrated the value of in vivo imaging in preclinical trials.
KW - Medical imaging
KW - Medical microbiology
KW - Virology
UR - http://www.scopus.com/inward/record.url?scp=85127118814&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.isci.2022.104101
DO - https://doi.org/10.1016/j.isci.2022.104101
M3 - Article
C2 - 35313622
SN - 2589-0042
VL - 25
JO - iScience
JF - iScience
IS - 4
M1 - 104101
ER -