Multimodal Molecular Imaging Reveals Tissue-Based T Cell Activation and Viral RNA Persistence for Up to Two Years Following COVID-19

[Osaca]

I've been waiting for this one for the past months.

Multimodal Molecular Imaging Reveals Tissue-Based T Cell Activation and Viral RNA Persistence for Up to Two Years Following COVID-19
The etiologic mechanisms of post-acute medical morbidities and unexplained symptoms (Long COVID) following SARS-CoV-2 infection are incompletely understood. There is growing evidence that viral persistence and immune dysregulation may play a major role. We performed whole-body positron emission tomography (PET) imaging in a cohort of 24 participants at time points ranging from 27 to 910 days following acute SARS-CoV-2 infection using a novel radiopharmaceutical agent, [18F]F-AraG, a highly selective tracer that allows for anatomical quantitation of activated T lymphocytes.

Tracer uptake in the post-acute COVID group, which included those with and without Long COVID symptoms, was significantly higher compared to pre-pandemic controls in many anatomical regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. Although T cell activation tended to be higher in participants imaged closer to the time of the acute illness, tracer uptake was increased in participants imaged up to 2.5 years following SARS-CoV-2 infection. We observed that T cell activation in spinal cord and gut wall was associated with the presence of Long COVID symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms. Notably, increased T cell activation in these tissues was also observed in many individuals without Long COVID.

Given the high [18F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization SARS-CoV-2 RNA and immunohistochemical studies in a subset of participants with Long COVID symptoms. We identified cellular SARS-CoV-2 RNA in rectosigmoid lamina propria tissue in all these participants, ranging from 158 to 676 days following initial COVID-19 illness, suggesting that tissue viral persistence could be associated with long-term immunological perturbations.

https://www.medrxiv.org/content/10....1?rss=1&utm_source=dlvr.it&utm_medium=twitter

 

[BrightCandle]

This is gold dust. Proof of viral persistence and where. This is great news for Long Covid sufferers so long as investment into multiple antivirals capable of clearing these reservoirs are done this is very treatable.

It's also I think interesting that many without symptoms have this too and how hard controls were to find. It looks like everyone who has caught Covid is in trouble. Why they don't develop the symptoms however is interesting and leaves open the fact that fixing this infection might not help people as it's not the cause of the disease process just the initiator.

I have high hopes for these tracer PET scans as they can be used to look for other viral infections and cell types and if applied to ME should show what and where and we might finally get some proof of smouldering infections.

 

[Vlad83]

Important study for sure. If I understand this tech correctly, it does not look for T cells activated to SARS-CoV-2 specifically, so except for gut lining that they biopsied, the other locations may have other pathogens that reactivated as a result of the SARS-CoV-2 infection, herpesviruses for example. Or there could be a mix.

 

[BrightCandle]

Amy Proal is leading a project that does binding to the virus and antibodies so hopefully no biopsies will be necessary. That is expected later this year but given this paper it will hopefully show the same thing with a less invasive process.

 

[Osaca]

One takeaway is certainly that ME/CFS researchers should try to advocate as much as possible to get HIV and Post-Ebola researchers involved in ME/CFS research. The team at UCSF seems to be producing as much Long-Covid research as all ME/CFS researchers combined produce ME/CFS research.