We next reverted to the SN-HCW group, in which small volume PBMC collections were available from the time of recruitment, enabling the targeted analysis of baseline T cells in those with the strongest RTC responses at week 16. NSP12-specific T cells were already detectable at the baseline in 79% of those SN-HCWs with the strongest NSP12 responses after exposure (Fig. 4b). NSP12 responses expanded in vivo on average 8.4-fold between recruitment and week 16, with no corresponding change in FEC responses (Fig. 4c and Extended Data Fig. 8d). We confirmed the expansion at week 16 of pre-existing RTC-specific T cells at the subpool (Extended Data Fig. 8e, f) and individual peptide (Fig. 4c and Extended Data Fig. 8g) levels. Moreover, many T cells were newly detected after exposure (Extended Data Fig. 8g), reflecting either de novo priming or expansion of responses that were previously below the limit of assay detection (example of expanded response undetectable by ex vivo ELISpot; Extended Data Fig. 8h). All of the HCWs with newly detected or expanding/contracting NSP12-specific T cells had both NP1- and NP2-reactive T cells after exposure (Extended Data Fig. 8i), whereas only 2 out of 5 individuals with no change in NSP12 had these specificities, suggesting that they may not have had the same level of SARS-CoV-2 exposure. The fold change in NSP12 between recruitment and the week 16 follow-up correlated with the total SARS-CoV-2 response, supporting its use to identify those seronegative individuals with expanded T cell immunity after exposure (Extended Data Fig. 8j).
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