Thread by @fitterhappierAJ

I've been comparing cov2 to ebola ever since I saw the lymphopenia in Jan in the Lancet. Nasty damn bug. Confuses the hell out of the immune system. theguardian.com/society/2021/j…

I really enjoy looking into Ebola, because when I started out at the NCI we had a phenomenon where we did not know the mechanism

Basically, a talented Physician before I arrived noticed memory T cells in a stimulation would differentiate pools of t cells further pubmed.ncbi.nlm.nih.gov/20971955/

The project evolved to where they noticed when Naive and memory t cells were costimulated, regardless of the antigen, whenever the MEMORY were stimulated the naive would differentiate faster, even if they proliferated less

When I joined I printed out ~50 papers and had a human immunology class as well, and we were assigned an essay on a disease of our choice. I picked the biggest and baddest boy- Ebola.

What I noticed it do to T cells, was cause them all to release gamma and die, just like the memory would do to the naive cells. The surg fellow on the project agreed to let me take it, as he went back to residency pubmed.ncbi.nlm.nih.gov/11227491/

So I mustered up courage and asked to block FASL in the context of t cell stimulation in 2011. Antibodies were ordered, the onc fellow that was going to flow the data on Sunday messaged me he couldn't make it.

So I went in and did it myself, and at 7 am Monday emailed all the lab the results. Murine cd8 T cells appeared to signal paracrine to differentiate each other via Fas, and it was feed-forward.

So we were able to withold Fas signalling and create better immunotherapies because of it. Also, Fas was signaling through AKT to create this effect. pubmed.ncbi.nlm.nih.gov/26657860/

Because of this mechanism of T cell differentiation and the highly differentiated cells Cov2 results in, I have a hypothesis that there is increased FasL signalling in Covid-19 onlinelibrary.wiley.com/doi/10.1111/bj…

Reviewers asked me, "but why? This does not fit into conventional models." So I had to justify it a bit with the poor IL-6 results at the time. I am happy IL-6 blockade is working now. frontiersin.org/articles/10.33…

So NEVER compare cov2 to flu. It is pushing the T cells too hard from my years of looking at bags of human T cells and their "age."

https://twitter.com/fitterhappierAJ/status/1292971091598684160

Well, the story is not 100 percent over. I am friends with a careful neuroscientist. He's a coauthor with me on the Frontiers paper. He and I read this paper in april and he was as concerned with the neurotropism as I was the lymphopenia

https://twitter.com/fitterhappierAJ/status/1306482669631537157

So yet another reason cov2 is not a flu. It needs to be taken seriously.

The predictive power of knowing differentiation and pathological processes works... I do not expect cd8 compartment resilience in the aged.

https://twitter.com/fitterhappierAJ/status/1293546396684103680

nature.com/articles/nm049…