Thread by @maini_lab

❗non-peer reviewed pre-print❗

Our latest work as part of covid-consortium.com @UKCICstudy

👩‍🔬Pre-existing polymerase-specific T cells expand in abortive seronegative #SARSCoV2 infection👨🏻‍🔬

medrxiv.org/content/10.110…

This has been an incredibly enjoyable and interesting project to work on - and huge thanks go to all participants (HCW and medical students are the best❗️), funders ...

@UKCICstudy @UKRI_News @NHSBartsHealth @NIHRresearch

... and the work of many fantastic co-authors 👏

@Leo1401j @BallouxFrancois @bertoletti_lab @mnoursad @AineMcKnight @JccmoonMoon @dr_manisty @BoytonRosemary @Daltmann10 @RealMcCoyLab @AnnaJS_viro @natha_schmidt @j_m_gibbons @OliMAmin @LucyvanDorp @ThomasTreibel @StephyKucyKousa

Short🧵- We identified a subset of HCW who were repeatedly PCR and serology negative (weekly during UK 1st wave) but had stronger SARS-CoV-2-specific #Tcells than pre-pandemic donors...

… and had a low-level increase in an innate blood transcriptomic signature of #SARSCoV2 infection, suggesting they experienced transient/abortive infection

What was special about their T cells? Unlike after infection, they often targeted the early expressed replication-transcription complex, including the polymerase…

…which is highly conserved with seasonal CoVs and is a common target of pre-existing cross-reactive T cells – that we showed expanded in vivo after exposure to #SARSCoV2 without seroconversion

Replication-transcription complex-specific #Tcells could complement spike antibodies for early #SARSCoV2 control & may offer reactivity to emerging & endemic Coronaviridae, arguing for their assessment in next-gen vaccines 🧬💉

Read the full paper here: medrxiv.org/content/10.110…