Is COVID prematurely aging our immune system?

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In a recent situation update, Ontario public health officials noted that there is emerging evidence that SARS-CoV-2 can cause “immune dysregulation,” a vague term used when the immune system is not behaving normally.

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White blood cell counts may be wrong, immune cells aren’t working as they should, inflammation is higher than it should be. “In short, COVID-19 causes permanent and potentially permanent changes in immune cells in some, but not all people,” said immunologist Dawn Bowdish of McMaster University.

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Research suggests 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 could prematurely age the human immune system.

The magnitude is not yet clear. However, “a potential increase in acquired impaired immunity in the Ontario population could have a significant impact on the occurrence and associated burden of infectious diseases … and other diseases over the longer term,” states the Public Health Ontario Evidence Letter.

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The concern is that in the future people will be less able to fight off pathogens and disease-causing agents like influenza, or that a troubled immune system could lead to an increase in diabetes and other autoimmune diseases.

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Public Health Ontario said its experts best suited to speak to the matter are busy with pandemic-related work and unable to elaborate. But the prospect of a compromised immune system in some people “shows that getting repeated infections with this thing is probably not good,” Toronto emergency room physician Kashif Pirzada said.

Bowdish sensed that an imbalance in the immune system, a key feature of long-standing COVID, could be a problem when she first looked at a blood sample from someone hospitalized with SARS-CoV-2. “We were trying to figure out why some people die in intensive care and others don’t,” Bowdish said. The blood “no longer looked like human blood. Their white blood cells were unrecognizable compared to healthy donors.”

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Her team has since published a small study showing abnormal white blood cell counts and severe inflammation in even asymptomatic and mild “recoveries,” although the problem is much more pronounced in people with severe cases of COVID.

“We learned that this virus, and we can’t tell you how, kills a whole bunch of T cells and then, at least in some people, causes damage to the white blood cells after that infection,” he said Bowdish, a Canadian Research Chair in Aging and Immunity. In some cases, blood cells never fully recover “and appear to generate autoimmune responses,” 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 patients with COVID.

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T cells have a life cycle, Pirzada said. Naïve cells are those that have not yet responded to 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 commit 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 less of it is a sign of “immune aging”. We have some resilience to make more naïve cells, Bowdish said, “but not unlimited capacity.”

Didn’t look like human blood anymore

She doesn’t want to sound too alarming. “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, these overzealous cells can cause chronic, increased inflammation, which is responsible for much of the damage inflicted on the body, said T cell researcher Anthony Leonardi.

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A group in Boston reported in June in advance that people with long COVID had persistent bits of spike protein — the protein that sticks to the outside of the virus — in their blood for up to a year after diagnosis, which could be a reservoir of infection.

“It could be that SARS-CoV-2 stays in the body and causes immune changes,” said Leonardi.

Others have reported that people with even mild infections had signs of T-cell “depletion,” and that people with multiple COVID infections had “poorer immune memory to SARS-CoV-2,” Leonardi said, making it easier to cope with be reinfected. “It was almost like her T-cells gave up the ghost.”

Vaccines and boosters still reduce the risk of serious infections. “Once you’ve committed T cells to the vaccine or virus, theoretically they should expand and activate as soon as they’re boosted,” Bowdish said.

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A review found that most people do to eradicate the virus and that current vaccines “elicit robust T-cell responses likely to contribute to remarkable protection against hospitalization or death.”

But when people lose naïve cells, they may be less responsive to other viruses or infections, “so that’s the main concern,” Bowdish said.

It’s not clear if the damaged T cells produce more inflammation, but persistent inflammation isn’t good. People are more likely to develop cardiovascular problems or strokes.

It’s also not clear if a lack of immune cells, as measured in the blood, means there are fewer of them, or if they’ve gone elsewhere in the body. “There is still a lot to learn,” said immunologist Tania Watts of the University of Toronto in an email.

“However, I agree with the school of thought that it is preferable to avoid this infection given the risks of a long COVID and evidence of long-lasting effects.”