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Immunocompromised patients show low immune response after second COVID-19 vaccination

Published: 07 July 2023

Many immunocompromised or immunosuppressed patients have shown a low or undetectable immune response after two doses of the same COVID-19 vaccine.

The findings come from new, preliminary data from the OCTAVE trial. The research is studying how clinically at-risk patients respond to infection and vaccination.

For the trial, patients who had the Alpha, Delta and Omicron strains of SARS-CoV-2 were studied up to one year after their first vaccination.

The research also showed the risk of severity and death from COVID-19 was high in a small sub-group of conditions, despite vaccination. This was particularly the case during the Delta wave.

The Omicron variant spread across the world last year and is now the dominant COVID-19 strain worldwide. Infection rates among at-risk patients rose but fewer of them became severely unwell or died.

OCTAVE study findings

There were 20 hospital sites across the UK which 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 15 people died from the disease.

Most infections (76%) occurred more than six months after the second vaccination. They occurred in patients with a kidney transplant, inflammatory arthritis and Crohn’s Disease. The majority of these infections were also first-time COVID-19 infections. Infections within six months of the second vaccination were not more severe than infections reported six months or later after vaccination.

Most infections (90%) were mild in severity, including some asymptomatic cases. Severe cases resulting in hospitalisation or death were reported in 9.8% of infections. They 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.

The rate of infection was higher in patients without a successful immune response to two COVID-19 vaccinations, compared to those with immune responses post-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 was 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.

State-of-the-art tests

The OCTAVE trial was set up in the middle of the COVID-19 pandemic. It is evaluating, in real time, the immune responses in patients with immune-mediated inflammatory diseases following COVID-19 vaccination. For example, cancer, inflammatory arthritis, diseases of the kidney or liver, or patients who are having a stem cell transplant.

The study is using state-of-the-art immune tests performed on blood samples taken before and after vaccination. It is studying infection and severity data to better understand the impact of a low vaccination response.

One of the largest studies in the world

In the UK, more than 60% of people aged over 65 are known to have one or more chronic disease. More than 12 million people aged 18-65 are 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.

The OCTAVE trial is one of the largest studies in the world into post-COVID vaccination in immunocompromised patients.

The study is published in Nature Medicine. It has been funded by the Medical Research Council and supported by the NIHR Clinical Research Network. It is a collaboration between the Universities of Glasgow, Birmingham and Oxford, and a consortium of other leading UK institutions.

‘Study pivotal in protecting most at risk’

Professor Andrew Ustianowski, NIHR Clinical Lead for the COVID-19 Vaccination Programme and Joint National Infection Specialty Lead said:

"COVID-19 is no longer the major problem that it was, largely as a result of the UK's world-leading vaccination research programme and roll-out. Vaccines however do not always provide equal protection in all our individuals, especially those with poor immune systems.

"The OCTAVE study has been pivotal in informing us on how best we should protect subgroups of our populations most at risk, so that we do not leave anyone behind in our fight to better protect all from the ongoing threat of coronavirus."

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