Whole-body visualization of SARS-CoV-2 biodistribution in vivo by immunoPET imaging in non-human primates, 2024, Naninck et al.

[SNT Gatchaman]

Whole-body visualization of SARS-CoV-2 biodistribution in vivo by immunoPET imaging in non-human primates
Thibaut Naninck; Alexandra Detrille; Steve Huvelle; Marit J. van Gils; Tatiana Geara; Quentin Pascal; Jonne Snitselaar; Laetitia Bossevot; Mariangela Cavarelli; Nathalie Bosquet; Francis Relouzat; Vanessa Contreras; Catherine Chapon; Fabien Caillé; Rogier Sanders; Roger Le Grand

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.

Link | PDF (Preprint: Research Square) [Open Access]

 

[SNT Gatchaman]

Study in non-human primates, following on from SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells (2023, Nature Immunology)

Here, we demonstrate the presence of the SARS-CoV-2 antigens by whole body immunoPET using a radiolabeled non-neutralizing monoclonal antibody that specifically targets a preserved epitope of the spike protein of the virus. We show persistence of the antigen in the lungs and brains of SARS-CoV-2 infected convalescent animals, as well as the distribution of the virus in various organs of acutely infected CMs [cynomolgus macaques].

For the first time, we were able to directly detect SARS-CoV-2 antigens in vivo using a non-invasive imaging technique. This approach, combining direct virus targeting and longitudinal follow-up, provides a powerful innovative tool to study COVID-19 pathophysiology and viral spreading. It can also provide insights for long-COVID studies, as well as potential treatment and vaccine efficacy studies in the future.

Surprisingly, we also found a visible PET signal at D3pi [day 3 post injection] in certain regions of the brains of both convalescent animals, with much higher SUV max values than in naïve animals (ratios of 0.80 and 0.63 for CM1 and CM2 versus 0.43 and 0.48 for the CM3 and CM4 controls). Moreover, radiotracer accumulation increased from D2pi to D3pi (2.55 ± 3.47%), whereas the radiotracer was eliminated in the mock + COVA (-42.62 ± 10.40%) group in the same brain region. Nevertheless, the average [89 Zr]COVA1-27-DFO uptake by the brain was similar and extremely low for all animals, indicating only localized uptake in these convalescent animals. Thus, the [89 Zr]COVA1-27-DFO radiotracer allows detection of the PET signal for SARS-CoV-2 spike antigen up to three months post initial infection in the lungs and brains of COVID-19 convalescent animals.

We also followed [89 Zr]COVA1-27-DFO and [89 Zr]IgG1-DFO uptake by various organs of interest over time in SARS-CoV-2-exposed or mock-exposed animals. First, there were no differences in [89 Zr]COVA1-27-DFO uptake by the brains between SARS-CoV-2-exposed and mock-exposed animals over time, with extremely low signals detected in this area, consistent with no crossing of the blood brain barrier by the [89 Zr]COVA1-27DFO mAb during the acute phase of infection.

 

[Hutan]

Paris/Amsterdam study

I think the importance of the study is not in showing that the CoV-2 antigens persist (as that has been done before), but that these researchers have a way of tracking their presence non-invasively in living animals. It might also be in demonstrating again that the antigens are getting into the brain - I'm not quite sure about that (see below).

They checked their imaging results by necroscopies.

They injected their tracer into monkeys 3 months after a CoV-2 infection and found persisting antigens. They also tracked the evolution of CoV-2 infections. They used a control radioactive tracer (no affinity for the CoV-2 antigen), and control monkeys (no infection).

I thought this was interesting about a kidney stone and the presence of the virus RNA in the kidneys:

CM10 [monkey 10], which showed 7-fold higher RNA titers in the kidneys (20,857 copies/250 ng total RNA) than CM9 (2,909 copies/250 ng total RNA) had a kidney stone, detected by CT (Fig. 10d, arrow), associated with local acute [89Zr]COVA1-27-DFO PET uptake (Fig. 10e, arrow). SARS-CoV-2 RNA was detected in the kidney collecting tubules (brown spots in Fig. 10f) of this animal in the same region. Overall, the postmortem tissue analysis corroborated the viral distribution in these organs measured by [89Zr]COVA1-27-DFO PET uptake

Low-dose [89Zr]COVA1-27-DFO injection does not allow accurate viral detection by PET

They tried a lower dose of the radioactive tracer and didn't get useful results. (Something to bear in mind for studies like these.)

Re the brain findings - this is in the animals 3 months after infection (they didn't find the antigen in the brains of the animals with the acute infection)

We also detected local accumulation of the radiotracer in areas of the brain of both convalescent animals from D2pi to D3pi, consistent with previous findings of neuroinflammation in humans infected with SARS-CoV-258 and in rhesus macaques up
to six weeks after SARS-CoV-2 infection59. The localized crossing of the blood-brain barrier (BBB) by the radiotracer in convalescent animals can be explained by thrombo-inflammation previously reported in patients with active long COVID60.

But have a look at figures 3h and 3i. There was no difference in the mean signals of the tracer in the convalescent and controls animals and they comment that the mean levels were low in all the animals. (Also, only two animals of each, which is understandable, given these are monkeys.) But there was a difference in the max values - so that's the 'local', in 'we also detected local accumulation of the radio tracer in areas of the brain'. So, it seemed to be just specific bits of the brain lighting up. They don't say what bits of the brain showed the signal.

 

[Hutan]

Just as an aside, I started reading 'Whole-body visualisation' and braced myself for what was to come. I wonder if you can get PTSD from constant exposure to BPS research?

 

[alktipping]

Just as an aside, I started reading 'Whole-body visualisation' and braced myself for what was to come. I wonder if you can get PTSD from constant exposure to BPS research?

Not PTSD just a high alert for bullshit because we have had to wade through so much .

 

[Dolphin]

Whole-body visualization of SARS-CoV-2 biodistribution in vivo by immunoPET imaging in non-human primates
Thibaut Naninck; Alexandra Detrille; Steve Huvelle; Marit J. van Gils; Tatiana Geara; Quentin Pascal; Jonne Snitselaar; Laetitia Bossevot; Mariangela Cavarelli; Nathalie Bosquet; Francis Relouzat; Vanessa Contreras; Catherine Chapon; Fabien Caillé; Rogier Sanders; Roger Le Grand

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.

Link | PDF (Preprint: Research Square) [Open Access]

Link doesn’t seem to be unique while pdf is https://assets-eu.researchsquare.co...-f525-43be-889a-027b8bba5975.pdf?c=1729649111
Weekly bulletin uses non-unique link.

 

[SNT Gatchaman]

Link doesn’t seem to be unique

Drats, I missed that error — thank you for pointing out. Research Square has incorrect metadata in its header. I've corrected this thread and asked for the News item to be corrected too.

 

[SNT Gatchaman]

Now published as —

Whole-body visualization of SARS-CoV-2 biodistribution in vivo by immunoPET imaging in non-human primates
Detrille, Alexandra; Huvelle, Steve; van Gils, Marit J.; Geara, Tatiana; Pascal, Quentin; Snitselaar, Jonne; Bossevot, Laetitia; Cavarelli, Mariangela; Dereuddre-Bosquet, Nathalie; Relouzat, Francis; Contreras, Vanessa; Chapon, Catherine; Caillé, Fabien; Sanders, Rogier W.; Le Grand, Roger; Naninck, Thibaut

The COVID-19 pandemic has caused at least 780 million cases globally. While available treatments and vaccines have reduced the mortality rate, spread and evolution of the virus are ongoing processes. 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 address 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 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 exhibit 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 allows viral detection in various organs, including the airways and kidneys, of exposed animals during the acute infection phase.

Overall, the technology we developed offers a comprehensive assessment of SARS-CoV-2 distribution in vivo and provides a promising approach for the non-invasive study of long-COVID pathophysiology.

Link | PDF (Nature Communications) [Open Access]