SARS-CoV-2 breakthrough infection induces rapid memory and de novo T cell responses

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Although the protective role of neutralizing antibodies against COVID-19 is well established, questions remain about the relative importance of cellular immunity. Using 6 pMHC multimers in a cohort with early and frequent sampling, we define the phenotype and kinetics of recalled and primary Tcell responses following Delta or Omicron breakthrough infection in previously vaccinated individuals. Recall of spike-specific CD4+ Tcells was rapid, with cellular proliferation and extensive activation evident as early as 1day post symptom onset. Similarly, spike-specific CD8+ Tcells were rapidly activated but showed variable degrees of expansion. The frequency of activated SARS-CoV-2-specific CD8+ Tcells at baseline and peak inversely correlated with peak SARS-CoV-2 RNA levels in nasal swabs and accelerated viral clearance. Our study demonstrates that a rapid and extensive recall of memory Tcell populations occurs early after breakthrough infection and suggests that CD8+ Tcells contribute to the control of viral replication in breakthrough SARS-CoV-2 infections.