A scientist at the Centre for Cancer Immunology has been involved in a study that shows, for the first time, the real-world vaccine responses and infection outcomes in clinically at-risk patients with a range of immunocompromised or immunosuppressed conditions.

Preliminary data from the landmark OCTAVE study in August 2021 showed that a significant proportion of clinically at-risk patients with immunocompromised or immunosuppressed conditions, mounted a low, or undetectable, immune response after two doses of the same SARS-CoV-2 vaccine. Now, in new peer-reviewed data, researchers are able to share the real-world infection outcomes for this clinically at-risk group.

Published in Nature Medicine, the latest findings reveal that while in most at-risk patient groups the overall COVID-19 infection rates were low, the risk of severity and death from SARS-CoV-2 was high in a sub-group of conditions, despite vaccination. This was particularly the case during the Delta wave. Furthermore, the data show that while Omicron, now the dominant SARS-CoV-2 strain worldwide, saw a rise of infection rate among at-risk patients, fewer of them became severely unwell or died.

This data covers the time from 2021 to mid-2022, and include patients infected with the alpha, delta and omicron strains of SARS-CoV-2. The data do not estimate the impact of third and fourth vaccinations, which have since been offered to patients in the groups studied.

The OCTAVE findings in detail:

  • There were 20 hospital sites across the UK who enrolled 2686 patients with reduced function of their immune systems to the trial.
  • Overall, 474 patients in the study became ill with COVID-19 up to one year after the date of their first vaccination. 111 of these infections were identified as either Alpha (1) or Delta (110) variants and 336 were identified as Omicron. 48 people were admitted to hospital because of a COVID-19 infection and sadly, 15 people died from the disease.
  • Most infections (76%) occurred more than six months after the second vaccination and were in patients with a kidney transplant, inflammatory arthritis and Crohn’s Disease. The majority of these infections were also first-time SARS-CoV-2 infections. Infections occurring within six months of the second vaccination were not more severe than those reported six months or longer post second vaccination.
  • Most infections (90%) were mild in severity, including some asymptomatic cases. Severe cases requiring hospitalisation or death was reported in 9.8% of infections and occurred predominantly in patients with renal disease. Patients infected in the Delta wave were more likely to have serious infection than those infected in the Omicron wave.
  • In patients who did not mount a successful immune response to two COVID-19 vaccinations, the rate of infection was higher when compared to those in the study that did mount an immune response after vaccination.
  • In some disease groups, the overall infection rates were low – possibly because of continued shielding at the time – but the proportion of severe cases within these groups were high. This was most notable in patients with ANCA Associated Vasculitis on rituximab, auto and allogeneic stem cell transplant and CART-T cell treated patients.
  • Low rates of severe disease were reported in patients with Crohn’s disease and ulcerative colitis.


Dr Sean Lim, Associate Professor and Honorary Consultant in Haematological Oncology at the University of Southampton, said: “While COVID seems like a memory for some of us, for many patients will compromised immune systems, the threat is still very real. Studies like OCTAVE provide us with important data and insight into how vaccines have provided protection for vulnerable people and how the variants impacted how effective they were. Importantly it’s shown us which patients, including some with renal diseases and some inflammatory conditions, who were not adequately protected, which will help us plan for the future. I’m very pleased we have been part of this important study, which is one of the largest studies in the world so far into post-SARS-CoV-2 vaccination in immunocompromised patients.”

OCTAVE (Observational Cohort Trial-T-cells Antibodies and Vaccine Efficacy in SARS-CoV-2) is a multi-centre, UK-wide trial led by the University of Glasgow, co-ordinated by the University of Birmingham’s Cancer Research UK Clinical Trials Unit and delivered by a national consortium of leading academic and clinical centres.

It was set up in the middle of the COVID-19 pandemic to evaluate, in real time, the immune responses following COVID-19 vaccination in patients with immune-mediated inflammatory diseases such as cancer, inflammatory arthritis, diseases of the kidney or liver, or patients who are having a stem cell transplant.