Non-severe SARS-CoV-2 infection is characterised by very early T cell proliferation independent of type 1 interferon responses and distinct from other acute respiratory viruses

We undertook T cell receptor sequencing in longitudinal blood samples in cohort of healthcare workers who experienced non-severe SARS-CoV-2 infection during the first epidemic wave in London to evaluate dynamic changes in the T cell clonal repertoire associated with infection. On the basis that an expanded clone will increase or decrease in frequency depending on the sampling time point before and after the peak response, we identified expanded TCR sequences as being statistically enriched at one time point compared to at least one other time point. These were compared to expanded sequences identified in the same way among a uninfected controls in whom we undertook TCR sequencing in samples from five successive weeks. By comparison to the pooled data from controls, a significant increase in expanded TCRs was evident in infected individuals by the time of the first positive PCR test up to a maximum abundance of >6% of total T cell sequences, and persisted for at least three weeks for both alpha and beta chains. Comparison with sequence data for known antigen reactive TCRs in VDJdb confirmed that expanded TCRs among infected individuals were most highly enriched for SARS-CoV-2 reactive T cells.