Almost a year ago I pointed out that the general population in Western countries seems to be suffering some degree of immunodeficiency. And the evidence for this assertion is stacking up. The T-cell immunologist Leonardi made some interesting points on Twitter that are worth emphasizing to me.
This study claims that after 2 years, long COVID patients show improvement of their immune dysregulation.
You have to look carefully at this graph, to see the trick. Red are the long COVID patients, blue the control group. At 3 months and 8 months, they show a higher percentage of PD-1 cells as a percentage of their CD3+ CD8+ T cells. Pd-1 is something your T cells produce to stop them from causing autoimmune problems, it tells them to shut down. It’s a signal you see when a T cell is exhausted.
So at 24 months, the two groups look the same. But what actually happened is not that the long COVID group got better, but that the control group now also shows increased T cell exhaustion!
And another study also found evidence of persistent T cell activation throughout the body, in both long COVID patients and a control group:
It’s not going to be a random subset of your CD8+ T-cells that suffer exhaustion. You would expect it to generally be the ones that have a T-cell receptor that matches some short protein chains found in SARS-COV-2.
If the whole population now has CD8+ T-cells that look for SARS-COV-2 infected cells that are showing signs of exhaustion, that means we’re becoming more vulnerable to the virus. Our immune system just won’t be as good anymore at destroying the cells that were infected by the virus as it used to be. The IgG4 antibodies have the same effect: It’s becoming harder for the immune system to destroy infected cells.
This is positive feedback: The virus damages those parts of the immune system that happen to fight the virus. This helps it establish persistent infections, which helps it spread easier to more people and helps it give rise to new variants. I would expect that more and more people are becoming persistently infected.
The question is what the consequences are of persistent infections. HIV results in a persistent infection, but so does cytomegalovirus. HIV can kill you within years without treatment, cytomegalovirus might cause some decline in immune function with age, but even that is disputed. I think a persistent COVID infection would be quite problematic, as it can infect the endothelial cells.
Of course this also blows a gaping hole in the idea that people are still protected through T-cell immunity against the virus by the vaccine despite the virus mutating away from the vaccines. If the CD8+ T cells that have to protect people against the virus by killing their infected cells are exhausted, that means they can’t properly protect them anymore.