Computed tomography and [18F]-FDG PET imaging provide additional readouts for COVID-19 pathogenesis and therapies evaluation in non-human primates

Thibaut Naninck; Nidhal Kahlaoui; Julien Lemaitre; Pauline Maisonnasse; Antoine De Mori; Quentin Pascal; Vanessa Contreras; Romain Marlin; Francis Relouzat; Benoît Delache; Cécile Hérate; Yoann Aldon; Marit van Gils; Nerea Zabaleta; Raphaël Ho Tsong Fang; Nathalie Bosquet; Rogier W Sanders; Luk H Vandenberghe; Catherine Chapon; Roger Le Grand

doi:10.1016/j.isci.2022.104101

Computed tomography and [¹⁸F]-FDG PET imaging provide additional readouts for COVID-19 pathogenesis and therapies evaluation in non-human primates

iScience. 2022 Apr 15;25(4):104101. doi: 10.1016/j.isci.2022.104101. Epub 2022 Mar 17.

Authors

Thibaut Naninck¹, Nidhal Kahlaoui¹, Julien Lemaitre¹, Pauline Maisonnasse¹, Antoine De Mori¹, Quentin Pascal¹, Vanessa Contreras¹, Romain Marlin¹, Francis Relouzat¹, Benoît Delache¹, Cécile Hérate¹, Yoann Aldon², Marit van Gils², Nerea Zabaleta^{3

4

5

6}, Raphaël Ho Tsong Fang¹, Nathalie Bosquet¹, Rogier W Sanders^{2

7}, Luk H Vandenberghe^{3

4

5

6}, Catherine Chapon¹, Roger Le Grand¹

Affiliations

¹ Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, Paris, France.
² Departments of Medical Microbiology of the Amsterdam UMC, Amsterdam Institute for Infection and Immunity, University of Amsterdam, 1105 Amsterdam, the Netherlands.
³ Grousbeck Gene Therapy Center, Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA 02114, USA.
⁴ Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA.
⁵ The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
⁶ Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
⁷ Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.

Abstract

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.

Keywords: Medical imaging; Medical microbiology; Virology.