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Controversy - What If COVID-19 Reinfections Wear Down Our Immunity? The Leonardi Effect

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  • Controversy - What If COVID-19 Reinfections Wear Down Our Immunity? The Leonardi Effect


    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.

    snip

    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.

    snip

    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.

    snip

    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.

    snip


    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.

    more...


    https://thetyee.ca/Analysis/2022/11/...ampaign=071122

  • #2
    Apparently he was correct.


    Media Advisory

    Monday, March 20, 2023

    SARS-CoV-2 infection weakens immune-cell response to vaccination


    NIH-funded study suggests need to boost CD8+ T cell response after infection.
    Colorized scanning electron micrograph of a cell (red) infected with the Omicron strain of SARS-CoV-2 virus particles (blue), isolated from a patient sample.NIAID


    What


    The magnitude and quality of a key immune cell’s response to vaccination with two doses of the Pfizer-BioNTech COVID-19 vaccine were considerably lower in people with prior SARS-CoV-2 infection compared to people without prior infection, a study has found. In addition, the level of this key immune cell that targets the SARS-CoV-2 spike protein was substantially lower in unvaccinated people with COVID-19 than in vaccinated people who had never been infected. Importantly, people who recover from SARS-CoV-2 infection and then get vaccinated are more protected than people who are unvaccinated. These findings, which suggest that the virus damages an important immune-cell response, were published today in the journal Immunity.

    The study was co-funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and led by Mark M. Davis, Ph.D. Dr. Davis is the director of the Stanford Institute for Immunity, Transplantation and Infection and a professor of microbiology and immunology at Stanford University School of Medicine in Palo Alto, California. He is also a Howard Hughes Medical Institute Investigator.

    Dr. Davis and colleagues designed a very sensitive tool to analyze how immune cells called CD4+ T cells and CD8+ T cells respond to SARS-CoV-2 infection and vaccination. These cells coordinate the immune system’s response to the virus and kill other cells that have been infected, helping prevent COVID-19. The tool was designed to identify T cells that target any of dozens of specific regions on the virus’s spike protein as well as some other viral regions. The Pfizer-BioNTech vaccine uses parts of the SARS-CoV-2 spike protein to elicit an immune response without causing infection.

    The investigators studied CD4+ and CD8+ T-cell responses in blood samples from three groups of volunteers. One group had never been infected with SARS-CoV-2 and received two doses of the Pfizer-BioNTech COVID-19 vaccine. The second group had previously been infected with SARS-CoV-2 and received two doses of the vaccine. The third group had COVID-19 and was unvaccinated.

    The researchers found that vaccination of people who had never been infected with SARS-CoV-2 induced robust CD4+ and CD8+ T-cell responses to the virus’ spike protein. In addition, these T cells produced multiple types of cell-signaling molecules called cytokines, which recruit other immune cells—including antibody-producing B cells—to fight pathogens. However, people who had been infected with SARS-CoV-2 prior to vaccination produced spike-specific CD8+ T cells at considerably lower levels—and with less functionality—than vaccinated people who had never been infected. Moreover, the researchers observed substantially lower levels of spike-specific CD8+ T cells in unvaccinated people with COVID-19 than in vaccinated people who had never been infected.

    Taken together, the investigators write, these findings suggest that SARS-CoV-2 infection damages the CD8+ T cell response, an effect akin to that observed in earlier studies showing long-term damage to the immune system after infection with viruses such as hepatitis C or HIV. The new findings highlight the need to develop vaccination strategies to specifically boost antiviral CD8+ T cell responses in people previously infected with SARS-CoV-2, the researchers conclude.

    Article


    F Gao, et al. Robust T cell responses to the Pfizer/BioNTech vaccine compared to infection and evidence of attenuated CD8+ T cell responses due to COVID-19. Immunity DOI: 10.1016/j.immuni.2023.03.005(link is external). (2023).

    Who


    Dan Rotrosen, M.D., director, NIAID Division of Allergy, Immunology and Transplantation, is available to respond to media requests for interviews.

    Comment


    • #3
      However, people who had been infected with SARS-CoV-2 prior to vaccination produced spike-specific CD8+ T cells at considerably lower levels—and with less functionality—than vaccinated people who had never been infected.
      But that could instead suggest that vaccination damages CD8+ T cell immunity when people have natural immunity. Probably unwise to draw any conclusions from a N=<10 study of natural immunity in test tubes.

      In the real world, I see volunteers/members aged 70-82 at the local adult wellness center (gym, etc), who are unvaccinated with Covid or with any other recommended adult vaccines, and they have recovered from Covid with no problems. They say they feel better than ever yet they spend hours in social situations where strangers are working out, playing pool, swimming, and loudly complaining about current public policies.

      If these people end up with later stage cancers or other progressed illness that could have been cured earlier, it won't be because of natural immunity to Covid. It will be because they start avoiding the doctors haranguing them to get vaccines they don't want.
      _____________________________________________

      Ask Congress to Investigate COVID Origins and Government Response to Pandemic.

      i love myself. the quietest. simplest. most powerful. revolution ever. ---- nayyirah waheed

      "...there’s an obvious contest that’s happening between different sectors of the colonial ruling class in this country. And they would, if they could, lump us into their beef, their struggle." ---- Omali Yeshitela, African People’s Socialist Party

      (My posts are not intended as advice or professional assessments of any kind.)
      Never forget Excalibur.

      Comment


      • Emily
        Emily commented
        Editing a comment
        Philosophy? I'm describing good health. It happens in real life. They aren't just not dead - they are thriving. They don't have to rationalize anything. Be glad some people feel healthy and strong. They are needed in society.

      • sharon sanders
        sharon sanders commented
        Editing a comment
        COVID-19 can cause real damage to the body especially after repeated infections. Do increased vaccine doses + repeated infections increase the likelihood of a bad outcome? Worse than repeated infections without the vaccine usage? Not proven or disproven yet. In the US the most deadly wave was the Delta wave in 2020 - before vaccines were available.

      • Emily
        Emily commented
        Editing a comment
        There were vaccinated during Delta, but the naturally immune were better protected than vaccinated. Even CDC admitted that. If they had just recommended vaccination for the vulnerable with no natural immunity, then I wouldn't have lost respect for their integrity at that point. But they persisted with that looney 'hybrid immunity' jazz. It was nonsense.


        New research from the Centers for Disease Control and Prevention and health officials in California and New York indicates that a prior case of Covid-19 protected people from infection better than vaccinations did during the delta wave last summer and fall.

        The findings, published Wednesday in the CDC's Morbidity and Mortality Weekly Report, appear to contradict public health messaging that pushes vaccinations.

    • #4
      However, people who had been infected with SARS-CoV-2 prior to vaccination produced spike-specific CD8+ T cells at considerably lower levels—and with less functionality—than vaccinated people who had never been infected.
      Again, the above supports damage to the immune system of naturally infected/immune people when they get an unneeded Covid vaccine. It has happened before- still is if they are using this vaccine instead of the old whole cell vaccine:


      James D Cherry, The 112-Year Odyssey of Pertussis and Pertussis Vaccines—Mistakes Made and Implications for the Future, Journal of the Pediatric Infectious Diseases Society, Volume 8, Issue 4, September 2019, Pages 334–341, https://doi.org/10.1093/jpids/piz005
      ...

      Because of the small number of antigens (3–5 in DTaP vaccines vs >3000 in DTwP vaccines), linked-epitope suppression occurs. Because of linked-epitope suppression, all children who were primed by DTaP vaccines will be more susceptible to pertussis throughout their lifetimes, and there is no easy way to decrease this increased lifetime susceptibility.
      _____________________________________________

      Ask Congress to Investigate COVID Origins and Government Response to Pandemic.

      i love myself. the quietest. simplest. most powerful. revolution ever. ---- nayyirah waheed

      "...there’s an obvious contest that’s happening between different sectors of the colonial ruling class in this country. And they would, if they could, lump us into their beef, their struggle." ---- Omali Yeshitela, African People’s Socialist Party

      (My posts are not intended as advice or professional assessments of any kind.)
      Never forget Excalibur.

      Comment


      • #5
        Second time - vaccine 6 months ago. First time unvaxxed she had a worse cough, this time she has lower oxygen. I did check and make sure she isn't alone. She seems better in her next video.


        I've got Covid ​ My Pomeranians, Chihuahua, and Chiweenie keep me company.

        Chronic Pomeranian Love

        14 subscribers

        39 views Mar 25, 2023 #chronicillness #servicedog #christianlife

        hello 👋🏽 everyone sorry this video is a few days late but I've got covid for the second time and it's been a doozy. anyways here's more about it ☺️ my name is Angelica and I am a young adult (I'll be 30 in a week but still consider myself young haha) who loves dogs, to write, travel, and am chronically ill. I am working on my first book which will be released later this year, When a Christian Meets Chronic illlness. My book is a devotional sharing different aspects of my life and how illness affects it, as well as encouraging others who go through similar experiences. You can learn more and also more about me at angelicalynnlove.com thanks for your support ❤️ on my site I have more stories about my dogs (in my blog) and share more about how I ended up where I am now. God bless
        _____________________________________________

        Ask Congress to Investigate COVID Origins and Government Response to Pandemic.

        i love myself. the quietest. simplest. most powerful. revolution ever. ---- nayyirah waheed

        "...there’s an obvious contest that’s happening between different sectors of the colonial ruling class in this country. And they would, if they could, lump us into their beef, their struggle." ---- Omali Yeshitela, African People’s Socialist Party

        (My posts are not intended as advice or professional assessments of any kind.)
        Never forget Excalibur.

        Comment


        • #6
          Originally posted by Emily View Post
          Second time - vaccine 6 months ago. First time unvaxxed she had a worse cough, this time she has lower oxygen. I did check and make sure she isn't alone. She seems better in her next video.

          There are bad outcomes of COVID-19 in people who have no vaccination. For example:

          Radiol Case Rep . Long COVID? Fatal case report of ischemic stroke and pulmonary embolism post COVID-19 infection


          Not all bad situations can be blamed on vaccines:

          JAMA - Association Between BNT162b2 Vaccination and Long COVID After Infections Not Requiring Hospitalization in Health Care Workers


          Repeat COVID-19 infections has been shown to increase disease severity - "The risks were evident regardless of vaccination status."

          Nature Medicine - Acute and postacute sequelae associated with SARS-CoV-2 reinfection - November 10, 2022

          Comment

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