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AJ Leonardi, MBBS, PhD Profile picture
@fitterhappierAJ
May 11, 2021 • 7 tweets • 4 min read • Read on X
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This is important:

B.1.617 has mutations that may *enhance* pathogenesis

A mutation at P681R in combination with L452R and E484Q significantly increases syncitia formation

This is when the cells fuse together, and it's linked to fatal disease.
2/ The Gupta lab found the mutations L452R/E484Q/P681R together significantly increase Syncitia formation.

This is a function of the polybasic cleavage site. Syncitia formation is linked to fatal diseasehttps://www.biorxiv.org/content/10.1101/2021.05.08.443253v1
3/ Syncitia are a way the virus kills T cells

This paper in Cell Death and Differentiation discusses how Syncitia internalize T cells in order to kill them

nature.com/articles/s4141…
4/The authors of this Cell Death and Differentiation paper note how the PRRA furin cleavage site gives Sars Cov 2 this notable property

It is able to gain this function from the Furin Cleavage site

The B.1617 with the three mutations is even better at it
nature.com/articles/s4141…
5/ I'm concerned; I find this property worrying- of fusing cells

T cells are important

Could this be contributing to the disaster in India?

This goes against what many people were saying, that over time the virus would attenuate.

How much time were they talking about?
6/ Could @MonicaGandhi9 have been right-

That T cells were helping control the pandemic in India, but then a new set of mutations abrogated T cell control better?
nature.com/articles/s4141…
Notably, the T cells taken in by the syncitia were mostly CD8+

Could this be contributing to the CD8 lymphopenia in Covid-19?

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More from @fitterhappierAJ

AJ Leonardi, MBBS, PhD Profile picture
Jan 11
Since 2020 I have been arguing that Covid harms T cells, the cells responsible for controlling viruses

I am going to go over this article in the Daily Mail that poses it as a "new" hypothesis by @_lukechafer
1/ Image
Image
Great article @_lukechafer

One thing I see is that the article claims rising infections are "prompting" scientists to ask if something else is going on

That "something else" has been clearly described many times by me in 2020 on twitter and in publications Covid harms T cells Image
Image
There is a second point about the 2025 publication about reduced numbers of T cells

Something I have been saying and published also since 2020 Image
Image
Read 7 tweets
AJ Leonardi, MBBS, PhD Profile picture
Jan 4
In August an immunologist declared the "Leonardi Effect" had received a "decent burial"

Fast forward to today: a new preprint shows what I warned about in 2020

Persistent SARS-CoV-2-induced impairment of CD8 T cell responses to community-acquired pathogens

I was right
1/5 Image
Key finding: Post-COVID patients show markedly reduced T cell reactivity to common pathogens (influenza, Staph, VCZ) which is evidence of lasting immune dysregulation favoring secondary infections and viral reactivation

Link:


2/5 biorxiv.org/content/10.648…Image
This is the scenario I described years ago: accelerated CD8 aging/paralysis/exhaustion/senescence, poorer control of pathogens.

We ignored it at our peril. Rising "mystery" infections, cancers, herpes flares? Not a coincidence
3/5 Image
Read 5 tweets
AJ Leonardi, MBBS, PhD Profile picture
Jan 1
This BMJ highlight on movement from "immunity debt" to COVID's direct role in immune harm is a welcome shift

The evidence on T cell dysregulation driving secondary risks has been mounting and it's good to see mainstream outlets engaging it seriously
1/ Image
Image
In 2020 I argued against "debt", emphasizing Covid's lymphomanipulative pathways (T cell apoptosis, exhaustion, aging) causing immune harm

This drew massive ire
Labeled "crank"/"fraud," threats of op-eds pressuring labs, and a rescinded postdoc

I sacrificed hugely for candor
2/ Image
Detractors confidently pushed alternate explanations and villified me back then

now, as data aligns with booming opportunistics, they're silent. no acknowledgment, no "perhaps we were harsh."
3/ Image
Image
Read 6 tweets
AJ Leonardi, MBBS, PhD Profile picture
Nov 5, 2025
In 2020 I wrote a paper claiming the lymphopenia in Covid included Apoptosis, or T cell death

I made this "extreme" claim after reading the 1st paper on Covid's clinical course

Now, a paper claims ongoing T cell death is shaping population immunity
1/ link.springer.com/article/10.118…
Here they start by suggesting the immune system is aging from covid and that aged immune systems are vulnerable

In 2020 I projected that if reinfections would occur, then we would be left with population-level prematurely aged immune systems
2/ Image
Image
Their meta-analysis concludes Covid is causing sustained T cell death

There is an alternative hypothesis that reverses causality, but it is ridiculous

However, I claimed in 2020 immune harm from covid would ↑ susceptibility to a sera-evading variant
3/ Image
Read 12 tweets
AJ Leonardi, MBBS, PhD Profile picture
Jun 22, 2024
@Bryce_Nickels This is absolutely false because he made a “noble lie” and said the N 95s would not work for the public to the public in order for there to be greater supply to healthcare workers only. This backfired.
@Bryce_Nickels The ethical approach was the truth. This is a similar noble lie by omission that the WHO made when they refused to declare Covid as airborne in order for impoverished health systems to provide “adequate” PPE per their regulations according to WHO standards
@Bryce_Nickels The end result was workers in impoverished systems were being given “adequate “PPE for droplet transmission, and many of them died, including sadly many in New York City.
Read 4 tweets
AJ Leonardi, MBBS, PhD Profile picture
Apr 6, 2024
When will H5N1 will go Human to Human?
Which is deadlier?
"The Covid pandemic has prepared me for an H5N1 pandemic"
Read 4 tweets

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