Whole-body visualization of SARS-CoV-2 biodistribution in vivo by immunoPET imaging in non-human primates

The COVID-19 pandemic has caused nearly 780 million cases globally. While available treatments and vaccines have allowed a reduction of the mortality rate, the spread of the virus is still evolving quickly, resulting in the emergence of new variants. Despite extensive research, the long-term impact of SARS-CoV-2 infection is still poorly understood and requires further investigation. Routine analysis provides limited access to the tissues of patients, necessitating alternative approaches to investigate viral dissemination in the organism. We addressed this issue by implementing a whole-body in vivo imaging strategy to longitudinally assess the biodistribution of SARS-CoV-2. We demonstrate in a COVID-19 non-human primate model that a single injection of non-neutralizing radiolabeled [89Zr]COVA1-27-DFO human monoclonal antibody targeting a preserved epitope of the SARS-CoV-2 spike protein allows longitudinal tracking of the virus by positron emission tomography with computed tomography (PET/CT). Convalescent animals exhibited a persistent [89Zr]COVA1-27-DFO PET signal in the lungs, as well as in the brain, three months following infection. This imaging approach also allowed detection of the virus in various organs, including the airways and kidneys, of exposed animals during the acute phase of infection. Overall, the technology we developed offers a comprehensive assessment of SARS-CoV-2 distribution in vivo and provides a new approach for the non- invasive study of long-COVID physiopathology.