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.
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 is supported by the NIHR Oxford Biomedical Research Centre (BRC) and the Nuffield Department of Medicine.
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.
Its latest publication, in the journal Nature Medicine, contains important new data on infection rates, disease severity and deaths in the patient groups, who were studied up to one year after their first vaccination. Data from the study cover the time period from 2021 to mid-2022, and include patients infected with the alpha, delta and omicron strains of SARS-CoV-2.
They do not estimate the impact of third and fourth vaccinations, which have since been offered to patients in the groups studied.
These new data show 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.
Earlier this year, another national trial, Stravinsky, was launched to gather up-to-date information on the impact of COVID-19, and future COVID-19 booster vaccinations, on people who are immune vulnerable. It is investigating whether an antibody test result can predict an individual’s risk of severe COVID-19 infection.
Previously, preliminary data released from OCTAVE in 2021 showed that while most patients mounted a successful immune response after two doses of the vaccine, some patients with certain immunosuppressed conditions mounted a low, or undetectable, immune response. The study found overall that 12% of patients on the trial failed to develop antibodies, with an additional 27% only generating low levels of antibodies. Some patients also failed to generate adequate T cell responses after vaccination. Vaccine failure rates were higher in some subgroups including patients with ANCA-associated vasculitis on the drug rituximab, patients receiving haemodialysis and also on immunosuppressive therapy, and patients who were solid organ transplant recipients.
The study used a variety of state-of-the-art immune tests performed on blood samples taken before and/or after COVID-19 vaccination, as well as infection and severity data on patients to better understand the real-world impact of a low vaccination response in these patient groups.
Professor Iain McInnes, lead of the OCTAVE trial, and Vice Principal and Head of the College of MVLS at the University of Glasgow, said: “The OCTAVE study has provided vital insights into the effectiveness of SARS-CoV-2-directed vaccines in some of our most vulnerable patient groups. The study’s key strengths include identifying the small number of patients who may not respond to the vaccines, enabling healthcare providers and policy makers to make the best decisions to protect these groups of people. Importantly the study has also been able to reassure us that the majority of our immunocompromised patients in the UK have been protected from severe COVID-19 by the vaccination programme.”
Professor Pamela Kearns, Director of the Cancer Research UK Clinical Trials Unit at the University of Birmingham, said: “OCTAVE provides an important understanding of how vaccines provided protection for many groups of the most clinically vulnerable, and how the variants of the disease affected how effective they were.
“We can see that there are areas of particular concern where vaccines didn’t adequately protect against COVID 19, including some patients with renal diseases and some inflammatory conditions. We’re immensely grateful for all those participants and each of the centres that took part to give us the clearest picture yet of how the most clinically vulnerable were protected, and where there are areas of weakness that need to be addressed.”
Professor Eleanor Barnes, Professor of Hepatology and Experimental Medicine at the University of Oxford’s Nuffield Department of Medicine and the Oxford BRC’s Co-Theme Lead for Life-saving Vaccines, said: “Importantly, both the T cells and antibody responses to vaccines were shown to protect against severe disease in immunocompromised patients.”
Dr Jonathan Pearce, Director of Strategy & Planning, Medical Research Council said: “The important findings of the OCTAVE study where critically enabled by the collaborative efforts of researchers, hospitals and participants from across the UK. Their combined commitment ensured that the study provided robust insights of value to our response to COVID-19 and for our preparation for future pandemics.”
The OCTAVE trial is one of the largest studies in the world so far into post-SARS-CoV-2 vaccination in immunocompromised patients and is funded by the Medical Research Council (MRC). OCTAVE is a collaborative research project involving groups in the Universities of Glasgow, Birmingham, Oxford, Liverpool, Imperial College London and Leeds Teaching Hospitals NHS Trust.