Thread by @MonicaGandhi9

T cell thread: Wanted to address T cells a bit more and why I think the AZ vaccine actually would work to prevent severe disease against the B.1.351 variant (although the S. Africa trial was not allowed to continue to show this outcome). So, remember that immunity comprises two

arms - antibody responses and T cells. T cells are the major immune defense against viruses. For instance, since the HIV virus infects CD4 cells, those with advanced HIV are susceptible to severe viral (and parasitic) infections. So, HIV doctors think about "T cells" a lot! Ok,

as discussed before, T cell responses to natural infection or vaccines help protect you against severe disease with SARS-CoV-2. Some papers below on this: a functional T cell response will modulate the severity of disease if you get infected or after vaccination.

One of my favorite papers on this is here showing efficient cellular T cell responses with natural infection lead to asymptomatic versus symptomatic SARS-CoV-2 infection. Good T-cell responses will protect you from severe infection if you see virus again
rupress.org/jem/article/21…

So, when we look across the vaccine trials and see the consistent response of high (almost 100%) protection against severe COVID-19 with all the vaccines, and even with circulating variants, T cells responses likely responsible. So, what about the AZ vaccine in S. Africa?

This paper shows that the efficacy of the AztraZeneca vaccine against mild-moderate SARS-CoV-2 in South Africa with B.1.351 was low (21.9%). However, seems like important finding in paper was missed: The AZ vaccine "caused expansion of CD4+ and
nejm.org/doi/10.1056/NE…

CD8+ T lymphocytes to specific epitopes of the spike protein. Of 87 spike-specific antigens identified by the sequencing, 75 REMAINED UNAFFECTED by the B.1.351 mutations." So, the B.1.351 viral mutations did NOT perturb the COVID-19 specific CD4 and CD8 T cell responses that

developed in response to the AZ vaccine! Doesn't that remind you of the complex CD4/CD8 response seen after natural infection (sciencedirect.com/science/articl…) or the paper showing vaccine-induced T-cell responses are PRESERVED against the variants? biorxiv.org/content/10.110…

including B.1.351 (S. Africa variant?). So, if the AZ trial had been allowed to proceed in S. Africa, we likely would have seen high reductions in severe disease from SARS-CoV-2 like we have seen from the AztraZeneca vaccine in the UK. For instance, the AZ vaccine

was highly protective against severe disease (ER and hospitalizations in England): medrxiv.org/content/10.110…
And this paper shows 94% protection against hospitalization with COVID-19 in Scotland with just 1 dose of the AZ vaccine: ed.ac.uk/files/atoms/fi…

So, if T cell induced immunity protects you against severe disease, then a re-infection in the future (when we won't be testing like we do now) will go unnoticed because it will be asymptomatic. So, take great heart in the T-cell immunity preserved against the B.1.351

variant in S. Africa in the NEJM paper. Still wish the U.S. had adopted UK approach of giving 1st dose of mRNA vaccines now to expand reach and then 2nd in 12 weeks like UK so our curves could look more like the UK curves. Also, vaccinated + vaccinated - no masks/distancing

I was accused today in an email of not worrying enough about the variants but the above thread is why (and there are plenty of people worrying about them already; you don't need me!). Moreover, in this study showing re-infection rare, authors state re-infections not admitted

to hospital ("detailed clinical parameters are not typically recorded unless the patient was admitted to hospital due to severe COVID-19 symptoms") so re-infections (when rarely do occur) not severe. From our protective T-cell immunity
sciencedirect.com/science/articl…

So what justifies lockdowns, masks, restriction of normal life? When severe disease high. Places of rapid vaccination (Israel, UK) seeing the severe disease melt away with vaccines so have specified dates of re-opening.

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