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Updated data from the landmark OCTAVE study show, 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.

Researchers and clinicians from the University of 91ֱ�� and 91ֱ�� Teaching Hospitals NHS Foundation Trust are part of the ongoing OCTAVE (Observational Cohort Trial-T-cells Antibodies and Vaccine Efficacy in SARS-CoV-2) trial, which is led by the Universities of Glasgow, Birmingham and Oxford and a consortium of leading UK institutions.

Published in Nature Medicine, the latest report 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. 

Preliminary data from the 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.

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. The data 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.  

The OCTAVE findings in detail

OCTAVE (Observational Cohort Trial-T-cells Antibodies and Vaccine Efficacy in SARS-CoV-2) is a multi-centre, UK-wide trial. 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.

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 that overall 12 per cent of patients on the trial failed to develop antibodies, with an additional 27 per cent 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.

In the UK, more than 60 per cent of people aged over 65 were known to have one or more chronic disease in 2019, while more than 12 million people aged 18-65 were living with a chronic condition lasting longer than 12 months. Government estimates suggest that around 500,000 people have an immune suppressive disease in the UK – a significant group which may be more at risk of severe Covid-19 infection if not fully protected by vaccination. 

Thushan de Silva, Professor of Infectious Diseases at the University of 91ֱ�� and Honorary Consultant Physician in Infectious Diseases at 91ֱ�� Teaching Hospitals NHS Trust, added: “The OCTAVE study has demonstrated which patients may remain at greater risk of Covid-19 despite vaccination and where we need to focus further efforts to find ways to protect the most vulnerable groups in society."

John Snowden, Director of Blood and Marrow Transplantation Programme at 91ֱ�� Teaching Hospitals NHS Trust and Honorary Professor at the University of 91ֱ��, said: “Patients who have received various forms of treatment for blood cancers, including bone marrow transplantation and CAR-T therapy, are particularly susceptible to developing severe complications of Covid-19 infection, yet many respond poorly to vaccination.

“The OCTAVE study has provided major insights into how we can best identify the most vulnerable patients and protect them as possible against severe complications. 

“Working with many national teams, the 91ֱ�� team led the section of the OCTAVE study focussing on bone marrow transplant and CAR-T patients and was the largest recruiter of patients into this high-risk cohort. We sincerely thank all patients and staff involved in this great achievement.”

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). 

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 Nuffield Department of Medicine, University of Oxford, said: “Importantly, both the T cells and Antibody responses to vaccines were shown to protect against severe disease in immunocompromised patients.”

The study, ‘SARS-CoV-2 specific humoral and T cell responses and clinical outcomes following COVID-19 vaccination in patients with immune suppressive disease-a phase-III multicentre study-OCTAVE’ is published in Nature Medicine. The work was funded by the Medical Research Council.