i've seen a lot of people today talking about this preprint (even though i think it came out a month ago?), but i'd like to sound a note of caution... https://twitter.com/rfsquared/status/1285294047872135168

the big headline figure is preexisting T-cell responses in 81% of unexposed individuals. but remember that T-cell repertoires are extremely diverse. this is how the whole system works. if you don't already have T cells in you that are specific to SARS2 peptides you're in trouble!

a large enough number of pre-existing T cells is prima facie evidence that these cells were expanded in response to a past infection. BUT! in this paper the authors use an approach to magnify the hell out of any T cells that were there.

specifically, they steep peripheral blood mononuclear cells with peptides for 12 days while also exposing them to IL-2. this approach isn't used, as far as i've seen, in other studies looking at T cells for SARS2. it's not crazy or anything, but it's designed to be v v sensitive

see e.g. this paper https://www.biorxiv.org/content/10.1101/760355v1.full.pdf which says that culturing PBMCs with peptides for many days increases the ELISPOT counts by 2 to 5 fold! in addition, the "81% positive" paper expresses ELISPOT results per 5 x 10^5 cells. most others use a 10^6 denominator

so to try to compare apples and oranges, you need take the numbers were and divide by maybe...10? it's messy. and by the end of it, i'm not sure we're saying anything more than random t-cell specificities

also worth remembering that in one of the other t-cell papers that a lot of people talked about (the swedish one where some exposed but seronegative family members were T-cell-positive), they report that *zero* out of 37 samples from healthy blood donors in 2019 were T-cell+

(they define "positive" as having "detectable T cell responses" against both N and one of M or S; not sure how they set up the peptide pools. fig 3A shows there are 2019 responses to all three to varying degrees, but not together)

a UK study likewise "did not detect any IFNγ-producing SARS-CoV-2-specific T cell responses in unexposed healthy volunteers" https://www.biorxiv.org/content/10.1101/2020.06.05.134551v1.full.pdf