Incredible project: developing a PET scan to reveal bodily locations of SARS-CoV-2 reservoirs in long COVID patients

[Hip]

An incredible project is underway to develop special PET scans which can detect the precise locations of viral infections in the body:

Article from Polybio website:
Total Body Pet Imaging To Identify Deep-Tissue SARS-CoV-2 Reservoirs In Long COVID

The team at University of California San Francisco plan to use radiolabeled monoclonal antibodies which bind to SARS-CoV-2 to identify tissue reservoirs of the virus in long COVID patients via a PET scan.

This is what a PET scan to detect SARS-CoV-2 in the body might look like:

If this works, the team plan to extend it to other viruses and bacteria, in patients with other chronic diseases:

If the project team can successfully image SARS-CoV-2 reservoirs in patients with Long COVID, they can begin to radiolabel therapeutics that target other pathogens implicated in human chronic disease. This would greatly increase the general understanding of pathogen persistence throughout the human body, with strong implications for cancer, Alzheimer’s disease, and other conditions increasingly tied to persistent viral or bacterial activity in tissue.

A new, more sensitive PET scanner is being used for this project.

A major strength of the project is that it pushes the boundaries of how imaging technologies can be used to identify persistent pathogens in the human body. The EXPLORER PET scanner that will be used in this study is the first FDA-approved full-body PET scanner and was created by two members of the project team.

The scanner has an effective sensitivity for total-body imaging that is 40-fold higher than current commercial scanners and is expected to revolutionize how PET imaging can be used in both biomedical research and ultimately in clinical practice. This video provides more information on the EXPLORER PET scanner and its innovative features.

Interview with project leader Dr Tim Henrich:

 

[Hip]

I always thought it would be amazing if we had the ability to scan the entire body of ME/CFS patients to detect all the bodily locations of viral infection.

It could be that there are some key locations which are infected in ME/CFS patients, and perhaps ME/CFS only occurs when there is an infection at these key locations. For example, the vagus nerve hypothesis of ME/CFS, which posits that ME/CFS occurs when the vagus nerve is chronically infected with a virus. This whole-body scan for SARS-CoV-2 may be able to detect any such critical key locations.

It seems that if this works for SARS-CoV-2, the team are going to try to extend the technology to other viruses and bacteria. This could be a massive step forward not only for ME/CFS, but for the many diseases which have been linked to chronic pathogenic infection in the tissues.

 

[junkcrap50]

Do we know the status or the progress of this project? Is it still only on paper or have they begun recruiting patients?

 

[cfs since 1998]

This is genius. Hope it works.

 

[marcjf]

I would not be surprised if they found virus in various tissues, but the problem is when you start adding controls to the comparison. They had a similar project, but not involving Sars-Cov-2, here: https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-020-00785-5
It did not involve a PET scan. They literally went and scooped the tissues of supposedly healthy (but dead) individuals, while checking for a multitude of viruses. It is pretty shocking, some of them, like EBV, are prevalent everywhere.

 

[Hip]

Do we know the status or the progress of this project?

At 8:40 in the video, Dr Tim Henrich says "we are doing this right now", referring to adding radiolabels to off-the-shelf monoclonal antibody products which bind to SARS-CoV-2. This video was posted in Feb 2023, so I am guessing they may have already injected these radiolabelled monoclonal antibodies into long COVID patients and PET scanned them.

Though I have not seen any published studies (here are Dr Henrich's papers on PubMed, and I cannot see any papers on this PET scan technique).

Interestingly, in that video, Dr Henrich says they have already successfully applied their technique to HIV patients, to detect HIV reservoirs in the body via a PET scan. So the technique seems to work for HIV.

 

[junkcrap50]

They literally went and scooped the tissues of supposedly healthy (but dead) individuals, while checking for a multitude of viruses. It is pretty shocking, some of them, like EBV, are prevalent everywhere.

Yes, this relates to a sort of a question I had.

Do we even know what (monoclonal antibody) antigens to be looking for in other pathogens? For COVID, there are some obvious antigen like spike, nucleocapsid, RBD, etc. This project is using spike protein mABs. The spike protein alone is pathogenic to many things in many ways.

For instance in EBV, which antigen protein should be selected? EBNA or VCA like typical antibody tests? dUPTASE? I'm sure there are a dozens more that I'm not aware of. I'm not sure if we even know of any EBV proteins that alone are pathogenic (maybe dUPTASE I guess), like the spike protein. The obvious solution would be to test multiple ones and compare to controls to see which matter, but that's essentially multiple studies.

 

[Hip]

Do we even know what (monoclonal antibody) antigens to be looking for in other pathogens?

For enterovirus infections I suspect the viral antigen would be the enterovirus VP1 viral protein.

Dr Chia uses the 5-D8/1 monoclonal antibody stain to highlight the location of enterovirus infection in stomach tissue biopsies of ME/CFS patients. This stain binds to VP1 and colours the tissues brown, as shown in images A and C below:

Dr John Chia uses the 5-D8/1 monoclonal antibody to reveal
enterovirus VP1 protein in the stomach biopsy tissues of ME/CFS
patients (the brown stains in images A and C), and uses the
J2 monoclonal antibody to reveal enterovirus dsRNA in the
stomach tissues (brown stains in images B and D).
100X magnification. Source: here. ​

This 5-D8/1 monoclonal antibody was first developed by Professor James Mowbray in the 1980s for the purpose of detecting enterovirus.

If this 5-D8/1 monoclonal antibody were radiolabelled, it might be usable in the PET scan.


Another option for detecting viral infection might be the J2 monoclonal antibody. This binds to dsRNA, which most viruses create when replicating in a cell. I don't think J2 will tell you which specific virus is present, because production of dsRNA is common to many viruses.

For instance in EBV, which antigen protein should be selected? EBNA or VCA like typical antibody tests? dUPTASE?

I am not sure which might be the best herpesvirus antigens to target.

Though researchers might want to bear in mind that Dr Lerner and others have theorised ME/CFS involves abortive herpesvirus infections, rather than productive herpesvirus. Abortive infections do not complete the viral lifecycle, and so do not produce full herpesvirus virions. But they nevertheless make many viral proteins.

So to detect these abortive infections (assuming they are indeed present in ME/CFS), you would want to target a protein antigen they make. I believe dUPTASE is made by herpesvirus abortive infections.

On the other hand, if we assume ME/CFS might involve partially reactivated latent herpesvirus infections, you might want to target a viral protein made in these partially reactivated latent states.

 

[Treeman]

It was good to see the excitement of them both.

For me the first question is time spans? How long for results?How long for treatments?

They talked about combination treatments and whilst at this time we don't know what to use as we don't know the combinations, there are some examples out there that could be considered on symptoms?

 

[Hip]

For me the first question is time spans? How long for results?How long for treatments?

I wouldn't think this study will directly lead to treatments (although you never know).

The study may help establish some basic science and basic understanding about ME/CFS: if the PET scans demonstrate that ME/CFS patients' bodies are lit up with widespread viral infection, whereas healthy controls are not, it may convince more researchers that ongoing infection underlies ME/CFS.

If the infection theory of ME/CFS gains more traction, then more research might be undertaken to try to understand why ME/CFS patients cannot properly control these viral infections, whereas most other people exposed to the same viruses can. Or more research might be directed towards developing new antivirals or immune stimulators.

At present our knowledge of where the ongoing viral infections lie in ME/CFS patients' bodies is very limited. We have biopsy studies showing enterovirus infection in the muscles, stomach and brain of patients; but there are many other organs and areas of the body which scientists have not biopsied, and so this study could revolutionise understanding of which organs are infected.

I've always wondered whether critical immune organs might be infected, which might then explain why the immune system cannot clear these infections in ME/CFS patients.


However, whether this PET scan can give information about where in the brain viral infections are located, I am not sure, because I don't think monoclonal antibody efficiently cross the blood-brain barrier.