Association of SARS-CoV-2 Spike Protein Antibody Vaccine Response With Infection Severity in Patients With Cancer A National COVID Cancer Cross-sectional Evaluation

Importance  Accurate identification of patient groups with the lowest level of protection following COVID-19 vaccination is important to better target resources and interventions for the most vulnerable populations. It is not known whether SARS-CoV-2 antibody testing has clinical utility for high-risk groups, such as people with cancer.


To evaluate whether spike protein antibody vaccine response (COV-S) following COVID-19 vaccination is associated with the risk of SARS-CoV-2 breakthrough infection or hospitalization among patients with cancer.

Design, Setting, and Participants  

This was a population-based cross-sectional study of patients with cancer from the UK as part of the National COVID Cancer Antibody Survey. Adults with a known or reported cancer diagnosis who had completed their primary SARS-CoV-2 vaccination schedule were included. This analysis ran from September 1, 2021, to March 4, 2022, a period covering the expansion of the UK’s third-dose vaccination booster program.


Anti–SARS-CoV-2 COV-S antibody test (Elecsys; Roche).

Main Outcomes and Measures  

Odds of SARS-CoV-2 breakthrough infection and COVID-19 hospitalization.


The evaluation comprised 4249 antibody test results from 3555 patients with cancer and 294 230 test results from 225 272 individuals in the noncancer population. The overall cohort of 228 827 individuals (patients with cancer and the noncancer population) comprised 298 479 antibody tests. The median age of the cohort was in the age band of 40 and 49 years and included 182 741 test results (61.22%) from women and 115 737 (38.78%) from men. There were 279 721 tests (93.72%) taken by individuals identifying as White or White British. Patients with cancer were more likely to have undetectable anti-S antibody responses than the general population (199 of 4249 test results [4.68%] vs 376 of 294 230 [0.13%]; P < .001). Patients with leukemia or lymphoma had the lowest antibody titers. In the cancer cohort, following multivariable correction, patients who had an undetectable antibody response were at much greater risk for SARS-CoV-2 breakthrough infection (odds ratio [OR], 3.05; 95% CI, 1.96-4.72; P < .001) and SARS-CoV-2–related hospitalization (OR, 6.48; 95% CI, 3.31-12.67; P < .001) than individuals who had a positive antibody response.

Conclusions and Relevance  

The findings of this cross-sectional study suggest that COV-S antibody testing allows the identification of patients with cancer who have the lowest level of antibody-derived protection from COVID-19. This study supports larger evaluations of SARS-CoV-2 antibody testing. Prevention of SARS-CoV-2 transmission to patients with cancer should be prioritized to minimize impact on cancer treatments and maximize quality of life for individuals with cancer during the ongoing pandemic.

Author list



  1. Department of Oncology, University of Oxford, Oxford, United Kingdom
  2. Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom
  3. University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
  4. UK Health Security Agency, London, United Kingdom
  5. Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
  6. Torbay and South Devon NHS Foundation Trust, Torquay, United Kingdom
  7. University of Leicester, Leicester, United Kingdom
  8. Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
  9. University of Leeds, Leeds, West Yorkshire, United Kingdom
  10. Leeds Institute of Medical Research at St James’s, University of Leeds, Leeds, United Kingdom
  11. Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
  12. Royal Free Hospital, London, United Kingdom
  13. University of Sheffield, Sheffield, United Kingdom
  14. University of Oxford, Oxford, United Kingdom
  15. Birmingham Medical School, University of Birmingham, Birmingham, United Kingdom
  16. NHS England, Leeds, United Kingdom
  17. Imperial College London, London, United Kingdom
  18. Royal Cornwall Hospitals Trust, Truro, United Kingdom
  19. Kent Oncology Centre, Maidstone and Tunbridge Wells NHS Trust, Kent, United Kingdom
  20. Blood Cancer UK, Edinburgh, United Kingdom
  21. University College London, London, United Kingdom
  22. Torbay and South Devon NHS Trust, Torquay, United Kingdom
  23. University Hospital Southampton, Southampton, United Kingdom
  24. Wye Valley NHS Foundation Trust, Herefordshire, United Kingdom
  25. Kent Oncology Centre, Maidstone, United Kingdom
  26. University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
  27. Royal College of Physicians, London, United Kingdom
  28. Guy's and St Thomas' Hospitals NHS Trust, London, United Kingdom
  29. University of Bristol, Bristol, United Kingdom
  30. University College London Hospitals NHS Foundation Trust, London, United Kingdom
  31. Norfolk and Norwich University Hospitals NHS Foundation Trust, Norfolk, United Kingdom
  32. Sandwell and West Birmingham Hospitals NHS Trust, United Kingdom
  33. Oxford Medical School, University of Oxford, Oxford, United Kingdom
  34. Royal United Hospitals Bath, Bath, United Kingdom
  35. Department of Oncology, Southampton University Hospitals, Southampton, United Kingdom
  36. UCLH/CRUK Lung Cancer Centre of Excellence, London, United Kingdom
  37. Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
  38. Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, Oxfordshire, United Kingdom
  39. Royal Marsden NHS Foundation Trust, United Kingdom
  40. William Harvey Research Institute, London, United Kingdom
  41. University of Southampton, United Kingdom


Lennard Y. W. Lee, DPhil1,2; Michael Tilby, MBChB3; Thomas Starkey, MSci2; Maria C. Ionescu, MSc4; Alex Burnett, MRCP5; Rosie Hattersley, MBChB6; Sam Khan, PhD7; Martin Little, MRes8; Justin K. H. Liu, MRCP9; James R. Platt, MRes10; Arvind Tripathy, MD11; Isabella Watts, BMBCh12; Sophie Therese Williams, MSc13; Nathan Appanna14; Youssra Al-Hajji15; Matthew Barnard, PhD4; Liza Benny, PhD4; Andrew Buckley, PhD4; Emma Cattell, PhD16; Vinton Cheng, DPhil9; James Clark, MBBChir17; Leonie Eastlake, BMBS18; Kate Gerrand, MSc4; Qamar Ghafoor, MBChB3; Simon Grumett, PhD3; Catherine Harper-Wynne, MD19; Rachel Kahn, MSc20; Alvin J. X. Lee, PhD21; Anna Lydon, MRCP22; Hayley McKenzie, PhD23; Hari Panneerselvam, MBBS24; Jennifer Pascoe, MRCP3; Grisma Patel, MRCP25; Vijay Patel, MBChB16; Vanessa Potter, PhD26; Amelia Randle, MRCP27; Anne S. Rigg, PhD28; Tim Robinson, PhD29; Rebecca Roylance, MRCP30; Tom Roques, MRCP31; Stefan Rozmanowski, MMath4; René L. Roux, MRCP8; Ketan Shah, DPhil8; Martin Sintler, MMedSci32; Harriet Taylor33; Tania Tillett, MBChB34; Mark Tuthill, PhD8; Sarah Williams, MRCP3; Andrew Beggs, PhD2; Tim Iveson, MD35; Siow Ming Lee, PhD36; Gary Middleton, MD37; Mark Middleton, PhD1; Andrew S. Protheroe, MD38; Matthew W. Fittall, PhD39; Tom Fowler, PhD40; Peter Johnson, MD41; for the UK COVID Cancer Programme

Novel Coronavirus SARS-CoV-2


JAMA Oncology