SARS-CoV-2 responsive T cell numbers and anti-Spike IgG levels are both associated with protection from COVID-19: A prospective cohort study in keyworkers

Immune correlates of protection from COVID-19 are incompletely understood. 2,826 keyworkers had T-SPOT^®DiscoverySARS-CoV-2 tests (measuring interferon-γ secreting, SARS-CoV-2 responsive T cells, Oxford Immunotec Ltd), and anti-Spike S1 domain IgG antibody levels (EuroImmun AG) performed on recruitment into a cohort study. 285/2,826 (10.1%) of participants had positive SARS-CoV-2 RT-PCR tests, predominantly associated with symptomatic illness, during 200 days followup. T cell responses to Spike, Nucleoprotein and Matrix proteins (SNM responses) were detected in some participants at recruitment, as were anti-Spike S1 IgG antibodies; higher levels of both were associated with protection from subsequent SARS-CoV-2 test positivity. In volunteers with moderate antibody responses, who represented 39% (252/654) of those with detectable anti-Spike IgG, protection was partial, and higher with higher circulating T cell SNM responses. SARS-CoV-2 responsive T cell numbers predict protection in individuals with low anti-Spike IgG responses; serology alone underestimates the proportion of the population protected after infection.