Thread by @fitterhappierAJ

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?