CoViD and immunity

What If COVID Reinfections Wear Down Our Immunity?

Dr. Anthony Leonardi is a lightning rod for debate. If he’s right, this pandemic poses a greater threat than widely assumed.


Andrew Nikiforuk YesterdayTheTyee.ca

Tyee contributing editor Andrew Nikiforuk is an award-winning journalist whose books and articles focus on epidemics, the energy industry, nature and more. T cells are a body’s key line of defence against infection. COVID infections can cause them to prematurely age, harm organs and become exhausted, warns Dr. Anthony Leonardi.

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Nearly three years into the pandemic, it’s clear early expectations about the behaviour of the coronavirus and its toll on our bodies have proven overly optimistic.

Recall those early days when experts broadly assumed that once we’d withstood an infection our immune systems would adjust and fully resist another reinfection.

And then hopes rose that mass vaccination would provide the path out of the pandemic. Although vaccines did reduce deaths and hospitalizations, the effort failed to produce herd immunity.

But researchers saw further promise in what they called hybrid immunity: people who had been infected with COVID and then received mRNA vaccines would, it was assumed, develop a formidable protection through raised levels of antibodies (proteins made by the immune system to battle infection).

However variants emerged, capable of evading those antibodies. Many people who had been vaccinated or already had endured a bout of COVID were experiencing “breakthrough infections.” What could put the brakes on this ever-evolving virus, which can kill, damage organs and linger for months?

The answer from many scientists has been T cells — our bodies’ line of immune defence after antibodies. T cells can spot and attack viruses and even remember previous invaders. As virologist Vincent Racaniello titled one of his articles: “T cells will save us from COVID-19.”

But what if COVID wears down T cells in people who get it, and does so increasingly with each reinfection?

That concern lies at the heart of a rolling, rancorous scientific debate, a lot of it conducted on Twitter. A person at the centre of the storm, sounding alarms about T cell “dysregulation” since the early days of the pandemic, has been a U.S. immunologist named Anthony Leonardi.

By dysregulation Leonardi means three effects of COVID:

• The hyperactivation of many T cells, which can prematurely age them
• The exuberant function of those hyperactivated T cells, which can then cause organ damage
• The exhaustion of those hyperactivated T cells, which implies they aren’t winning the battle against viral proteins they are supposed to defeat.

In other words, argues Leonardi, T cells are becoming hyperactivated by SARS-CoV-2 and are prematurely aging, harming organs, and becoming exhausted trying to rid the body of an immune-evasive virus.

If he is right, then no, we cannot assume that T cells will save us — not as thoroughly, at least, as we’ve been led to believe.

Which is why The Tyee decided Anthony Leonardi and his controversial assertions merit a deep dive.

Leonardi’s critics say he paints too dire a picture. Some prominent researchers have accused him of being misguided, their tweeted insults scathing.

Reached by The Tyee, Leonardi did not apologize for the pessimistic edge to his warnings. “Optimism sells and optimism around T-cell memory sold well too.” Rather than practice a “passive conventionalism” that pretends the pandemic is over, he said, public health officials “need to be candid with the public.”

In a recent tweet Leonardi punched back at his most vociferous attackers, saying:

“All I have done is warn people and people find the warnings unpalatable. Not only that, people have given opinions on the trajectory of the virus and the immunology and have been blatantly wrong and are seeking a pound of flesh out of anger.”


A BAD FEELING

To understand why Leonardi is such a lightning rod requires a bit more discussion about how the human immune system works. It is composed of two complementary branches: one directed by antibodies and another mediated by T cells.

T cells are one of two white blood cells that defend the body against foreign invaders. (The other are B cells, which make antibodies.)

The human body supports millions of both T and B cells.

T cells, which originate in bone marrow and then mature in the thymus, perform multiple different roles as the human body matures and ages. Some T cells, for example, regulate the immune response while others directly bind to and kill cells infected by cancer or viruses. Others survey the body for signs of cancer. And some are simply “naive”: young cells not yet stimulated by an antigen.

Another group known as memory T cells can remember a foreign invader and lead the charge against reinfection. T cells can also secrete chemicals that help B cells produce antibodies. As a general rule T cells protect against reinfection by providing durable memory of past invaders.

Which is why it’s a big deal if Leonardi is correct in his belief that COVID exhausts, ages and cumulatively wears down the immune system with each infection.

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And then along came the pandemic. In the Twitterverse he was one of the first scientists to openly speculate about COVID’s ability to disarm the immune system. He reasoned that a weakened immune system would have profound implications for the severity of disease, the effectiveness of vaccines and the health of the elderly over the course of the pandemic.

Given nearly five years of work on T cells, Leonardi got a bad feeling while reading a Lancet study that appeared at the beginning of the pandemic.

The study described the unhealthy state of the first patients in Wuhan, China. Scientists noted that the virus had diminished the patient’s white blood cells — the ones responsible for fighting infection. Moreover descriptions of the patients suggested that a blood infection might be contributing to shock and death. That profile looked like a super antigenic infection whereby a particular molecule has set off an extreme immune response. As a result the immune system began to attack the body, it appeared to Leonardi.

Lots of viruses can set off autoimmune reactions in select populations, but Leonardi thought COVID might have the potential to unsettle the general health of the globe, and even change life expectancy patterns.

Readings on the long-term health impact of the original SARS virus and its cousin MERS also alarmed Leonardi.

These pathogens also disrupted the immune system. MERS, for example, not only infected and killed the cells lining blood walls but T cells as well. Both SARS and MERS could overcome the defences of the immune system, and result in prolonged chronic illness that lasted years.

To Leonardi the ramifications seemed highly significant. It meant that repeated waves of COVID infection might not leave durable or competent memory to fight reinfection or to clear the virus. Repeat infections could get worse over time resulting in more death, organ damage and long-term disability. He started writing letters to school boards and issuing warnings about his conclusions based on his extensive readings.

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The uproar reached a fever peak this year when Leonardi speculated that repeated COVID infections could exhaust T cells in people 50 years or older leading to a blunted immune response. (Chronic infections such as HIV or Epstein-Barr virus typically exhaust T cells.)

Leonardi first offered this opinion in August 2020 but it gained currency as reinfections skyrocketed with Omicron.

So, too, did the naysaying. Early this year, Vincent Rajkumar, the editor of Blood Cancer Journal, called the idea “nonsense,” as did U.S. virologists Vincent Racaniello and Amy Rosenfeld.

In January, sociologist and New York Times writer Zeynep Tufecki implied Leonardi was a solo outlier not to be trusted, tweeting:

“Reminder that not every crank is Galileo. Yes, experts can be wrong, even a field can be wrong — we saw with airborne — but challenges involve *groups* of actual working, publishing scientists.”

One of the barbs often tossed at Leonardi by critics is that he is not ensconced in a lab churning out results from experiments, so he doesn’t really belong to the club of researchers seriously trying to crack COVID. Leonardi is in fact a PhD accredited immunologist currently pursuing a master’s degree in public health.

One high-profile T cell expert among Leonardi’s harshest critics is Duke University scientist Antonio Bertoletti, who often ends his Twitter posts with “Go T Cells Go.” On Twitter he posted a Nature study on health-care workers claiming that it showed that “exposure [to COVID] broadens T-cell repertoire,” and that there was no problem with exhaustion.

However, the paper only looked at working age people and did not include individuals with long COVID in which chronic and persistent infection inflames the immune system.

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The Leonardi Effect may well explain a surge in bacterial, viral and fungal infections after waves of COVID.


And yet, it remains key for each of us to wear masks, keep socially distanced, and inhabit spaces lightly populated with good ventilation, if only, by Leonardi’s analysis, to stave off reinfection given the chance that each one grinds down our immune systems.

In recent weeks U.S. virologists such as Jeremy Kamil have expressed little concern about recent hospitalization rates in Europe and new immune-evasive variants. Kamil, for example doesn’t expect “a catastrophic” wave from “antibody-evasive convergent variants” in the future.

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