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

10.1126/sciimmunol.abf3698

Science Immunology

Contributing to research themes:

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.

Author list:

Catherine J. Reynolds1,, Leo Swadling2,, Joseph M. Gibbons3,, Corinna Pade3,, Melanie P. Jensen4, Mariana O. Diniz2, Nathalie M. Schmidt2, David K. Butler1, Oliver E. Amin2, Sasha N. L. Bailey1, Sam M. Murray1, Franziska P. Pieper1, Stephen Taylor5, Jessica Jones5, Meleri Jones3,6, Wing-Yiu Jason Lee3, Joshua Rosenheim2, Aneesh Chandran2, George Joy4, Cecilia Di Genova7, Nigel Temperton7, Jonathan Lambourne8, Teresa Cutino-Moguel9, Mervyn Andiapen4, Marianna Fontana10, Angelique Smit10, Amanda Semper5, Ben O’Brien4,11,12, Benjamin Chain2, Tim Brooks5, Charlotte Manisty4,13, Thomas Treibel4,13, James C. Moon4,13, COVIDsortium investigators$, Mahdad Noursadeghi2, COVIDsortium immune correlates network$, Daniel M. Altmann14,, Mala K. Maini2,, Áine McKnight3, and Rosemary J. Boyton1,15,,*

  1. Department of Infectious Disease, Imperial College London, London, UK.
  2. Division of Infection and Immunity, University College London, London, UK.
  3. Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  4. Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.
  5. National Infection Service, Public Health England, Porton Down, UK.
  6. Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  7. Viral Pseudotype Unit, Medway School of Pharmacy, Chatham Maritime, Kent, UK.
  8. Department of Infection, Barts Health NHS Trust, London, UK.
  9. Department of Virology, Barts Health NHS Trust, London, UK.
  10. Royal Free London NHS Foundation Trust, London, UK.
  11. William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  12. German Heart Centre and Charité University, Berlin, Germany.
  13. Institute of Cardiovascular Science, University College London, UK.
  14. Department of Immunology and Inflammation, Imperial College London, London, UK.
  15. Lung Division, Royal Brompton & Harefield NHS Foundation Trust, London, UK.
  • † These authors contributed equally.
  • ‡ Joint senior authors.
  • $ The members of the COVIDsortium investigators and COVIDsortium immune correlates network can be found at the end of the Acknowledgments.