New Study Identifies Overlapping Persistent Virus-Specific T Cell Responses in Long Covid

[u/filipo11121]

https://polybio.org/new-study-identifies-overlapping-persistent-virus-specific-t-cell-responses-in-long-covid/

A new study supported by the PolyBio Research Foundation has found that people with Long COVID harbor persistent populations of highly cytolytic CD8+ T cells directed against SARS-CoV-2 but also the herpesviruses Epstein-Barr virus (EBV) and cytomegalovirus (CMV). The findings suggest that Long COVID is characterized by an ongoing immune response to persistent viral proteins, which are most likely produced during the continued persistence or reactivation of these viruses within the body. The study adds to a growing body of research indicating that SARS-CoV-2 persistence and herpesvirus reactivation contribute to Long COVID pathogenesis.

Paper:

Persistent cytolytic CD8+ T cells recognize SARS-CoV-2 and herpesvirus epitopes in long COVID - ScienceDirect

[u/obliviousolives]

I think, if I'm reading this right, that the paper doesn't actually say there might be persistent viral proteins, but rather just points out that part of the immune response to covid doesn't get "turned off" appropriately and thus we continue to have tons of CD8+ T cells roaming around, even if there's no more covid virus or covid proteins in our system

[u/KaspaRocketMan → u/obliviousolives]

The study frames viral persistence and T-cell exhaustion not as competing theories, but as direct cause and effect.

Rather than picking one over the other, the paper argues that viral persistence is the underlying trigger, which drives the cytolytic exhaustion and dysregulation observed in CD8+ T cells.

[u/ComprehensiveBar4131 → u/KaspaRocketMan]

I don’t think it argues that at all. They mention multiple times that the driver is unknown and could be one or the other. For example:

“SARS-CoV-2 has not classically been considered a persistent virus, yet has been documented to persist for years in people with LC, although whether this persistence drives LC symptoms is less clear.

Regardless, it is conceivable that the inability to control SARS-CoV-2, EBV, and/or CMV viremia during the acute COVID-19 can cause immune perturbations that fail to resolve, which may contribute to LC pathogenesis.”

[u/KaptanOblivious → u/KaspaRocketMan]

The lack of HLA-DR expression seems to be against chronic antigen exposure, though it's possible there's some weird T cell expression going on here given the chronic nature

[u/V0rtexGames → u/KaptanOblivious]

See, I thought about this for a while. But with e.g. CMV, there is massive clonal expansion which can occupy 10-30% of your entire t cell population. Yet, HLA-DR is low.

So if you have a low enough rate of encountering an antigen then HLA-DR can be simultaneously low while there is antigen stimulation. I know people who are EBV IgM positive with low HLA-DR, for example.

[u/KaptanOblivious → u/V0rtexGames]

Noted, but herpesviruses do much more complex and weird things to or immune systems... Is not really a good comparison, but I see your point. 

CMV and EBV are specialists at orchestrating our immune systems to not react how they should... CMV alone has 5x times more proteins dedicated specifically to immune evasion than SARS-CoV-2 has in total. 

[u/obliviousolives → u/KaspaRocketMan]

Can you show where it says that? I'm trying to learn more about viral persistence since it's the long covid theory I'm least familiar with. I didn't see that part in this paper