OCTAVE study reveals vaccine response in patients with impaired immune systems

Researchers and clinicians from the University of Sheffield and Sheffield 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

• There were 20 hospital sites across the UK who enrolled 2,686 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 per cent) 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 per cent) were mild in severity, including some asymptomatic cases. Severe cases requiring hospitalisation or death was reported in 9.8 per cent 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.

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.

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.

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.