Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection

Reynolds, Catherine J.; Swadling, Leo; Gibbons, Joseph M.; Pade, Corinna; Jensen, Melanie P.; Diniz, Mariana O.; Schmidt, Nathalie M.; Butler, David K.; Amin, Oliver E.; Bailey, Sasha N. L.; Murray, Sam M.; Pieper, Franziska P.; Taylor, Stephen; Jones, Jessica; Jones, Meleri; Lee, Wing-Yiu Jason; Rosenheim, Joshua; Chandran, Aneesh; Joy, George; Di Genova, Cecilia; Temperton, Nigel; Lambourne, Jonathan; Cutino-Moguel, Teresa; Andiapen, Mervyn; Fontana, Marianna; Smit, Angelique; Semper, Amanda; O’Brien, Ben; Chain, Benjamin; Brooks, Tim; Manisty, Charlotte; Treibel, Thomas; Moon, James C.; Noursadeghi, Mahdad; Altmann, Daniel M.; Maini, Mala K.; McKnight, Áine; Boyton, Rosemary J.

Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.