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Kashif Pirzada, MD Profile picture
@KashPrime
Feb 20, 2022 • 72 tweets • 26 min read • Read on X
Why isn’t the pandemic over yet? Why did we require boosters? Authorities including the CDC are finally acknowledging that our vaccines provide protection for only 3-4 months at a time. I interview @fitterhappierAJ to go over possible reasons why.
I’ve been closely following @fitterhappierAJ’s takes on Covid and immunology. Initially I didn’t want to believe his predictions regarding T-cells, but they have stood the test of time and are now being confirmed by multiple lab studies
This is part of a lecture series by @masks4canada, to chart future directions of this pandemic. What can we do to change course, or at least ameliorate ill effects? Many of our political leaders want this to be over now, is this realistic? This is what we hope to address.
This is a simplified model of how our immune system works. We prevent infection with barriers like masks, and kill viruses when they get to our 2nd line of defence, our innate immunity and antibodies. If that fails, we have T-cells, which are efficient killers of infected cells. Image
What is the crux of Dr. AJ's arguments? We have been told that though the virus has mutated and is evading antibodies, our T-cells will save us. Problem is, these cells are themselves overactivated and damaged during infection, and start to damage you; the gets worse with age. Image
Papers that show continuing dysfunction in T-cells:
In Long Covid patients: nature.com/articles/s4159…
In severe Covid-19 disease: nature.com/articles/s4141…
Precipitates EBV reactivation:
doi.org/10.1016/j.cell…
Seen in lung damage on autopsy studies:
nature.com/articles/s4146…
The immune system depends on a fine balance and order to protect you. Invasion by a virus sets off your ‘innate immunity’ which sends signals, one of which is a chemical called Interferon, which ‘interferes’ with the virus. Your immune systems moves to quickly kill the invader. Image
Problem is, as @WmHaseltine explains in an excellent article series, that SARS2 is expert at hiding and preventing that signal from going out. Your cells are hijacked to create trillions of virus copies. T-cells go into overdrive to fight this.
forbes.com/sites/williamh…
SARS disables this essential early warning signal, Interferon. How severe a disease you get seems determined by how much this important early signal gets damaged.
nature.com/articles/s4159…
What happens is an overreaction; T-cells start killing healthy cells and each other, and you start depleting them, including your naive T-cells. Naive T-cells are a pool of cells that your body creates when you’re a child to handle future infections. Image
When these get depleted, it ages your immune system and likely leaves you open to future infections or cancers.
Low naive T-cells are associated with poor outcomes in this paper: pubmed.ncbi.nlm.nih.gov/33010815/ Image
This whole cascade seems to be prevented if you have antibodies circulating already that can sound the alarm on their own, which comes from recent infection or vaccination. Problem is your levels drop after 3-4 months. Maybe more boosters will keep them up longer.
This study from Singapore of Covid cases and close contacts shows that an antibody response was crucial in stopping infections:
doi.org/10.15252/emmm.… Image
A novel idea proposed by Dr. AJ is that naive T-cells act as a sink, a dampener on T-cell over-activation. He has a paper coming that will be explain in more detail, but this would go a long way to explain why age seems to the be predominant factor in death. Image
Younger people have more naive T-cells naturally, and if they act as a dampener on T-cell overactivation, would explain why those below 60 fare much better. The analogy is to carbon rods in stopping a nuclear chain reaction.
ncbi.nlm.nih.gov/labs/pmc/artic… Image
UK and US agencies are recently noticing the short duration of vaccine derived immunity:
cdc.gov/mmwr/volumes/7… Image
More and more papers are demonstrating poor long term outcomes post Covid infection. Many of these are in unvaccinated cohorts though, but the role of immune overactivation is becoming clearer and clearer Image
Image
Given the the risks to all age groups, especially the risk of death to those above 60, caused by T-cell overactivation and depletion, our leaders need to plan to prevent as many infections as possible. Image
I personally am planning to stay under circulating antibody protection as long as possible via boosters. Antibodies will allow your body to coordinate a defense against SARS2, prevent innate immunity evasion, and hopefully prevent Long Covid. Image
We need to build safe common spaces, ventilation upgrades, rapid tests and generally protecting as many as possible while restoring life to as close to near normal conditions as is possible. Image
This includes planning for surges and lulls in case numbers, where society can periodically recharge from high risk periods. Image
The alternative, where we do nothing and pretend things are over, is a dark future in which life expectancy is shortened, and many of us will not get to enjoy the fruits of our labours and a healthy old age
This is already being noticed by the insurance industry, where life insurance claims for those 18-64 are up 40%, an age group usually in good health.
thecentersquare.com/indiana/indian…
What is the solution? Improved vaccines are not far away, including intranasal vaccines. These have the benefit of being able to train your innate immunity, and the cells that line your nose and lungs to fight SARS2, and prevent it from evading immunity.
cell.com/cell/fulltext/… Image
I would caution against removing all pandemic protections. Much of the decision making is guided by political considerations and, in the case of Blue states, by focus group research, not sound science. It is not 'Mission Accomplished' unfortunately
nytimes.com/2022/02/10/pod… Image
Again, a link to the interview is here:
A transcript of the interview can be found here: docs.google.com/document/d/1-5…
A 32% increase in life insurance claims at Hartford Insurance Group:
Reupping this, sadly it looks like many places in the West are not preserving even basic measures. The results will be predictable, especially in those over 60 without regular boosters. Based on what you've learned in this thread, you now know better.
A fantastic thread discussing the value of Intranasal vaccines, mucosal immunity and long lived memory B cells:
An interesting treatment that could potentially reverse immune system aging: nature.com/articles/d4158…
#leonardiwasright
More verification:
And @fitterhappierAJ’s paper has just dropped! Hopefully will try to come up with a thread to explain it.
Some clarification:
Right on cue:
Reinfection leads to increased ICU admission in this study; immune system exhaustion would be a good explanation why:
More discussion on Superantigens and Superantigen-like motifs here:
Immune cell derangements and Long Covid:
Others are questioning if T-cells alone can fight off Covid without antibodies to help:
More evidence of viral suppression of immune activation and innate immunity that we reference in the video and this thread:
It doesn't take much to tip into exponential spread, when the R0 is close to 1...
A grand unified theory on the origins of MIS-C as well as severe Covid, featuring the Superantigen. Reinforces the point that we just can’t coexist safely with a super contagious superantigen carrying virus.
Links to earlier papers by @fitterhappierAJ that elaborate on this:
It's very important that @fitterhappierAJ be properly acknowledged for discovering this mechanism >2 years ago.
We have a sick scientific establishment that worships authority and pathologizes new ideas and directions. This is a centuries old problem.
Image
An older paper from China, in the pre-vaccine era, showing T cell depletion after infection. Could explain why they’ve been so adamant on controlling Covid infection. There are geopolitical stakes here, it seems, that leaders in the West are scarcely aware of.
More immunologists are speaking out about the serious derangement that happens with SARS2. This individual had 4 vaccines, and still developed acute Covid related cardiomyopathy and heart failure. This is simply not something you can endure 4x a year.
Wow! Public Health Ontario, in its latest assessment, strongly recommends bringing back public health measures in light of the prospect of recurrent, repeated SARS2 infections, and the prospect of immune system dysregulation. @fitterhappierAJ
Image
More evidence, as @fitterhappierAJ predicted, that your T cells don’t do well post SARS2 infection, especially if you’re older than 50:
Note the exhausted T-cells in this excellent study of Long Covid by @VirusesImmunity
Death-rate estimates from @MoriartyLab are consistent with @fitterhappierAJ's Naive T-cell hypothesis. If you're older than 50-60, your wisest strategy is to get boosted, avoid infection as much as possible, and advocate for masks/better indoor air quality
While a new study does not find Superantigenic activity from the spike protein itself, @fitterhappierAJ argues this activity could be coming from viral induced reactivation of latent viruses like EBV, explaining post-SARS2 T-cell exhaustion and depletion:
Great explanation of @fitterhappierAJ’s theory of age-related decline in T-cell effectiveness against SARS2 by @dr_kkjetelina. If you’re over 50, boosters are a good thing to get.

yourlocalepidemiologist.substack.com/p/why-older-pe… Image
As predicted, subsequent infections of SARS2 results in greater, cumulative pathology along nearly every body system. And remember, these are survivors, as the most susceptible have already died.
Excellent and detailed profile of @fitterhappierAJ‘s work in @TheTyee. You may need to read it 3-4X but you’ll never take SARS2 lightly again once you do:

thetyee.ca/Analysis/2022/…
easychair.substack.com/p/immune-dysre…

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More from @KashPrime

Kashif Pirzada, MD Profile picture
Sep 17
Noticing a lot of your relatives are just not the same, health wise? Relatives dying after surgeries that were relatively low risk a few years ago? Today, this report from insurance giant @SwissRe puts numbers on the ongoing excess death toll attributable to Covid-19.

From the report:

"Fluctuations in excess mortality tend to be short-term, reflecting developments such as a large-scale medical breakthrough or the negative impact of a large epidemic. However, as society absorbs these events, excess mortality should revert to the baseline.

With COVID-19 this has not been the case and all-cause excess mortality is still above the pre-pandemic baseline. In 2021, excess mortality spiked to 23% above the 2019 baseline in the US, and 11% in the UK. As Swiss Re Institute's report estimates, in 2023, it remained significantly elevated in the range of 3–7% for the US, and 5–8% for the UK.

If the underlying drivers of current excess mortality continue, Swiss Re Institute's analysis estimates that excess mortality may remain as high as 3% for the US and 2.5% for the UK by 2033."

What does the percentage increase in deaths mean in real numbers? Roughly 3 million people die in the US every year of various causes (cancer, heart disease, accidents, etc). The 3-7% increase in 2023 represents a 3-7% increase in that 3m number, so roughly 90-210k more deaths. This places Covid-19 solidly among the top five killers in the US, with heart disease (700k), cancer (600k), accidents (200k) and strokes (150k), and it continues to stay there 3 years after mass vaccinations, and countless waves and variants since.

While not the killer of millions and the destroyer of health systems it was in 2020-2021, it is a leading cause of death that we must continue to respect, and take active measures to prevent in especially the elderly and vulnerable. It continues to be a leading cause of disability in the form of Long Covid.Image
Here is a link to the report from Swiss Re:
swissre.com/press-release/…
Exactly, they keep blaming the vaccines 3y ago, and not the infection by a rapidly mutating virus everyone gets 1-2x a year.
Read 4 tweets
Kashif Pirzada, MD Profile picture
Aug 10
Probably the most important article you'll read all year, by @omeraziz12 in the @globeandmail
Canada is in serious trouble, and Aziz hits the nail on the head on the causes:

- Deep incompetence by politicians, who resort to PR management over making decisions. Parliament is deeply dysfunctional, with Question Period a joke, and committee hearings a farce. Trudeau but also the provincial premiers have much to answer for. Many of our leaders come from legacy wealthy backgrounds and have absolutely no idea how difficult they've made life for Canadians.

"What I realized soon thereafter was that this country was witnessing a systemic political failure, a complete inability of politicians to get change done in ways that manifested at the dinner table. An extreme form of PR and image-management had begun to take over delivering on policy in concrete ways − and the entire country was noticing. Nor was this an accident, the unfortunate consequence of polarization or inequality, but the deliberate result of multiple policy failures − as well as failures of will."

"Normally, in a democracy, social ills can be addressed by public officials. But Canada’s own political institutions have been riven by corruption and personal ambition. And now also potentially by foreign influence. Each controversy and scandal leads people away from crucial time and policy attention that could have been spent on fixing the country’s major issues. At the parliamentary level, most members of Parliament are so frightened of speaking for themselves that they are rendered powerless. This defies the very essence of the British parliamentary system, upon which Canada’s system is based, which empowers MPs to speak on behalf of their constituents and represent their true voice in the people’s chamber."

- Inattention to rising crime, especially rampant car thefts, a revolving door criminal justice system, neglect of the opioid crisis. We have the laxest justice system in the Western world. Causing someone's death will get you a 6 month sentence in one prominent example. America had mass incarceration, we have mass leniency.

"At some point, one would think that the deaths of so many innocent and vulnerable people would elicit outrage − yet life goes on as normal. Each life is precious, and when violent criminals get off easy, or without punishment at all, they learn the terrible lesson that this country does not take its own laws seriously, so why should they? When the law loses its power to deter crime, either because of prosecutors not moving forward with cases, or because of a general laissez-faire attitude toward violent crime happening in other neighbourhoods, it is the marginalized who are harmed most."

- Rising housing costs that has made nearly everyone, including me, to paraphrase A Bittersweet Symphony, a slave to massive mortgages until they die, or they are perennial renters.

"For many Canadians, the cost of living has become unaffordable. The average price of a house in the GTA is $1.1-million, and Metro Vancouver is around the same. There are certainly cheaper places to live, but the average cost of a rental in Canada has reached record highs − more than $2,100 a month. According to one major study, Canada needs to build an additional 3.5 million homes by the end of the decade and is currently only building around 200,000 a year."

- Violation of the social contract on immigration.
"In Canada, the social contract for years allowed more immigration to grow the economy, but this came with stringent criteria for who should be admitted. Today, there are more than 900,000 international students in Canada, a 170-per-cent increase over the past decade. Some of these students have been scammed by for-profit colleges. Others have been affiliated with fake schools, using their student visas as loopholes in the immigration system. The social system was unprepared for such an influx, though certain institutions benefited: colleges and universities got more fees; politicians touted rising immigration numbers; the landlord class got an endless supply of perpetual renters. Without any housing available, this has left the country unprepared to deal with multiple, overlapping economic and social crises."

Aziz asks What is the Canadian dream?
"It was a promise − less individualistic and gun-friendly than the American version, but no less ambitious. To me, the dream promised that every person here could have a decent shot at life, one that was better than that of their parents. There was emphasis on community and a strong focus on order and good government. The compact included the payment of higher taxes, and in exchange, the existence of world-class social institutions delivering for ordinary people. The immigration system worked because the same contract existed with immigrants − that they would work hard, play by the rules, become part of Canadian society through legal means, and in return, would become citizens of a highly functioning democracy where a good life was, if not guaranteed, then within reach.

The dream was based on fairness, on merit, on policies that worked. It promised breathable air and the bountiful resources of the second-largest country on Earth. It promised the principle of equality of opportunity, promised safety and peace and responsibility. It promised leaders who put the national and long-term interests of the country above their own partisan needs. The dream now feels like it’s on life support."

AmenImage
Link to the article here:
theglobeandmail.com/opinion/articl…
Read 4 tweets
Kashif Pirzada, MD Profile picture
Mar 6
Wanted to share with you something near and dear to my heart.
Today my colleagues and I are proud to launch the Canadian Covid Society. @CanCovSoc

Covid-19 is thankfully not the threat it once was, but there are still significant issues with having a new disease roughly 4x as bad as Flu (and much more contagious) floating around, which also disables a lot of people as well.

In Canada it was the 3rd leading cause of death 2020, 2021 and 2022. We have the Canadian Cancer Society, and Heart and Stroke foundation for the 1st and 2nd causes, it's time we have one for the 3rd leading cause of death.

It is perfectly natural to not want to deal with this issue anymore. But that's part of the problem isn't it?
Many of us have a visceral aversion to discussing it, perhaps a natural reaction to memories of the most traumatizing days of the pandemic. But the fact remains that it's still out there, that it will continue to cause strain on our health systems, disable people, and shorten life for many of us.

We need a national body that will keep advocating for things like updated vaccines and therapies, as well as common-sense fixes that prevent the spread of disease, like cleaner indoor air (which could have been very useful stopping this nasty measles outbreak we're having).

We need a national strategy to support and improve access to care for Long Covid sufferers, many of whom are simply unable to access any care for a devastatingly disabling condition. 2 out of the 3 Long Covid advocates we approached for our launch event were not able to attend due to illness, which should tell you something! There's no way to predict who will get it, when they'll get it, and there is no cure, yet.

We are organizing a virtual press conference for 1pm (ET) today, Wednesday March 6, 2024. A video stream will begin on Youtube, and this url will forward you there: . Journalists who wish to ask questions please send me a DM and I will send you instructions to join.

Our website is up at

You'll hear more from us as we grow the range of activities offered by the Society. We would love to share resources and help like-minded groups start national societies in their own countries. Would love to see and collaborate with an American Covid Society, a British Covid Society etc.

It is time that we create a permanent effort to fight this disease, and not have these efforts subject to political whims or a societal wish to indulge in denial.covidsociety.com
covidsociety.caImage
Image
Image
As a national society, we will be bilingual and our launch event will be in both French and English
lapresse.ca/dialogue/opini…
Read 8 tweets
Kashif Pirzada, MD Profile picture
Nov 28, 2023
Life expectancy drops for a third year in a row

C19 is the third leading cause of death, behind heart disease and cancer, ahead of accidents/trauma.

Mortality overall is up 13% across all age groups compared to 2019, and increasing every year

This should be a huge scandal! Image
We are being robbed of precious life years, for no good reason except to maintain an unsustainable status quo. We are losing time with our loved ones, the economy is losing out on workers in their prime years, and there must be a better way.

Media article:
Statscan source:
and
Does this look like a trend that's slowing down?
Not to me Image
Read 6 tweets
Kashif Pirzada, MD Profile picture
Jun 13, 2023
So much truth in this one graphic.
True story, on a recent shift, I had to run and help a patient who had collapsed on our waiting room floor, short of breath. Hypoxemic. The family was diligent, and tested before coming, and lo-and-behold, they were positive. With some help, got… twitter.com/i/web/status/1… Image
I asked ChatGPT to summarize my feelings in verse, and it did an astonishing job:

In sorrow do I witness suffering's reign,
The public's decline, inflicted by this bane,
The young struck by blood clots, strokes untold,
Life's flame grows dimmer, as the years unfold.
Alas,… twitter.com/i/web/status/1…
Thanks to @RobbieMeriales for the illustration:
Read 5 tweets
Kashif Pirzada, MD Profile picture
Jun 7, 2023
Today wore an N95 mask outside for the first time ever, and found it really helpful for throat irritation and that annoying choking feeling. Doesn't help for eye irritation though. Would highly recommend.
If you've upgraded your home, workplace or school with enhanced ventilation and filtration to fight airborne illnesses, you're in luck: staying indoors will protect you. If not, you can jerry-rig some filters using commonly available parts:
If you've spent time in any congested Asian or African city, the feeling is both routine and hard to forget. Even more reason to push hard the energy transition away from polluting and global-warming contributing fuels around the world.
Read 6 tweets

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