Thread by @maini_lab

🚨Advance publication out today in @Nature🚨
Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2
nature.com/articles/s4158…

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

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
@BennyChain

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 subclinical/abortive infection

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

…which is highly conserved across the Coronaviridae family and across all clades/variants of SARS-CoV-2 and importantly it is a common target of pre-existing cross-reactive T cells.

Through longitudinal analysis we showed that pre-existing replication-transcription complex/polymerase-reactive T cells were enriched before exposure and preferentially expanded in vivo after exposure in seronegative HCW with abortive infection.

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