Healthcare workers with mild / asymptomatic SARS-CoV-2 infection show T cell responses and neutralising antibodies after the first wave

Reynolds, C. J.; Swadling, L.; Gibbons, J. M.; Pade, C.; Jensen, M.; Diniz, M. O.; Schmidt, N. M.; Butler, D. K.; Amin, O. E.; Bailey, S. N. L.; Talyor, S.; Jones, J.; Jones, M.; Lee, W. Y. J.; Rosenheim, J.; Chandran, A.; Joy, G.; Di Genova, C.; Temperton, N. J.; Lambourne, J.; Cutino-Moguel, T.; Andiapen, M.; Fontana, M.; Smit, A.; Semper, A.; O'Brien, B.; Chain, B.; Brooks, T.; Manisty, C.; Treibel, T.; Moon, J.; COVIDsortium Investigators,; Noursadeghi, M. C.; COVIDsortium Immune correlates network,; Altmann, D. M.; Mani, M. K.; McKnight, A.; Boyton, R. J.

Studies of adaptive immunity to SARS-CoV-2 include characterisation of lethal, severe and mild cases. Understanding how long immunity lasts in people who have had mild or asymptomatic infection is crucial. Healthcare worker (HCW) cohorts exposed to and infected by SARS-CoV-2 during the early stages of the pandemic are an invaluable resource to study this question. The UK COVIDsortium is a longitudinal, London hospital HCW cohort, followed from the time of UK lockdown; weekly PCR, serology and symptom diaries allowed capture of asymptomatic infection around the time of onset, so duration of immunity could be tracked. Here, we conduct a cross-sectional, case-control, sub-study of 136 HCW at 16-18 weeks after UK lockdown, with 76 having had laboratory-confirmed SARS-CoV-2 mild or asymptomatic infection. Neutralising antibodies (nAb) were present in 90% of infected HCW sampled after the first wave; titres, likely to correlate with functional protection, were present in 66% at 16-18 weeks. T cell responses tended to be lower in asymptomatic infected HCW than those reporting case-definition symptoms of COVID-19, while nAb titres were maintained irrespective of symptoms. T cell and antibody responses were discordant. HCW lacking nAb also showed undetectable T cells to Spike protein but had T cells of other specificities. Our findings suggest that the majority of HCW with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multi-specific T cell responses for at least 4 months after mild or asymptomatic SARS-CoV-2 infection.