In a recent situation update, Ontario public health officials noted that evidence is emerging SARS-CoV-2 can cause “immune dysregulation,” a vague term that’s used when the immune system isn’t behaving normally.
White blood cell counts may be off, immune cells don’t work the way they should, inflammation is higher than it should be. “Long story short, COVID-19 leads to lasting, and possibly permanent changes in immune cells in some, but not all, people,” McMaster University immunologist Dawn Bowdish said.
Research is suggesting that T cells, the cells that help produce antibodies and kill infected cells, are taking a particular hit, and that repeated SARS-CoV-2 infections may be prematurely aging human immune systems.
The scale isn’t yet clear. However, “a potential increase in acquired impaired immunity in the Ontario population could have significant impact on the incidence and associated burden of infectious diseases ….and other conditions in the longer-term,” reads the Public Health Ontario evidence brief.
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The concern is that people will be less able to hold off future bugs and pathogens like influenza, or that unsettled immune systems could lead to an increase in diabetes and other auto-immune diseases.
Public Health Ontario said its experts best suited to speak to the matter were tied up on pandemic-related work and unavailable to elaborate. But the prospect of discombobulated immune systems among some people “highlights that getting repeated infections of this thing is probably not a good thing,” said Toronto emergency doctor Kashif Pirzada.
Bowdish sensed that immune imbalance, a key feature of long COVID, might be a problem the first time she looked at a blood sample from someone hospitalized with SARS-CoV-2. “We were trying to figure out why some people die in the ICU and others don’t,” said Bowdish. The blood “didn’t look like human blood anymore. Their white blood cells were unrecognizable compared to healthy donors.”
Her team has since published a small study showing abnormal white blood cell counts and high inflammation even in asymptomatic and mild “recoverees,” though the problem is much more pronounced in people with severe cases of COVID.
“We’ve learned that this virus, and we can’t tell you how, leads to the death of a whole bunch of T cells, and then seems to, at least in some people, lead to damage to the white blood cells they make after that infection,” said Bowdish, a Canada research chair in aging and immunity. In some cases, the blood cells never fully recover “and seem to generate auto-immune reactions,” where the body’s immune system attacks its own tissues.
A recent study published in Nature found lower numbers of “naïve” T and B cells (cells that produce antibodies) in those who had COVID.
T cells have a life cycle, Pirzada said. Naïve cells are those that haven’t yet responded to an infection. “Once a T cell commits to responding to one thing, it can’t respond to anything else,” Bowdish explained. “As we age, more and more of them become committed to responding to infections, or all the other things we might be exposed to, and fewer and fewer are available to respond to new threats.”
Having fewer of them is a sign of “immune aging.” We have some resilience to make more naïve cells, Bowdish said, “but not an indefinite capacity.”
Didn’t look like human blood anymore
She doesn’t want to sound too alarmist. “Many, hopefully most people, will be fine.” It’s also not entirely clear what’s at play.
One theory is that SARS-CoV-2 hyperactivates T cells, and, in severe cases, those overzealous cells can cause chronic, elevated inflammation that’s responsible for a lot of the harm done to the body, said T cell researcher Anthony Leonardi.
A group in Boston reported in preprint in June that people with long COVID had persistent pieces of spike protein — the protein that studs the outside of the virus — in their blood up to a year, post-diagnosis, which could be a reservoir of infection.
“It could be that SARS-CoV-2 is remaining in the body and causing immune alterations,” Leonardi said.
Others have reported that people with even mild-ish infections had signs of T cell “exhaustion,” and that people with multiple infections of COVID had “poorer performing immune memory to SARS-CoV-2,” Leonardi said, making it easier to be reinfected. “It was almost as if their T cells were giving up the ghost.”
Vaccines and boosters are still lowering the risk of severe infections. “Once you’ve got T cells committed to the vaccine or the virus, in theory these should be expanded and activated once you are boosted,” Bowdish said.
A review found that most people do eradicate the virus, and that current vaccines “elicit robust T cell responses that likely contribute to remarkable protection against hospitalization or death.”
But if people are losing naïve cells, they may be less likely to respond to other viruses or infections, “so that’s the major concern,” Bowdish said.
It’s not clear if the damaged T cells are producing more inflammation, but persistent inflammation isn’t good. People are more likely to develop cardiovascular problems or strokes.
It’s also not clear whether a lack of immune cells measured in blood means there are fewer of them, or they’ve gone somewhere else in the body. “Much remains to be learned,” University of Toronto immunologist Tania Watts said in an email.
“However, I agree with the school of thought that it is preferable to avoid this infection, because of the risks of long COVID and evidence of long-lasting effects.”
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