Study shows low or undetectable immune response to double COVID-19 vaccination in patients with impaired immune systems

The first data from the ongoing OCTAVE (Observational Cohort Trial-T-cells Antibodies and Vaccine Efficacy in SARS-CoV-2) study show that a significant proportion of clinically at-risk patients with certain immunocompromised or immunosuppressed conditions mount a low or undetectable immune response after two doses of the same COVID-19 vaccine.

The OCTAVE study – a multi-centre UK-wide trial led by the University of Glasgow and co-ordinated by the University of Birmingham’s Cancer Research UK Clinical Trials Unit – is evaluating the immune responses to 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.

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.

The study used a variety of state-of-the-art immune tests performed on blood samples taken before and/or after COVID-19 vaccination in around 600 people recruited across the UK.

• OCTAVE’s early data shows that 40% of people in the patient groups studied mounted a low serological immune response after two SARS-CoV-2 vaccines. 
• The initial data shows that approximately 11% of immunocompromised patients fail to generate any antibodies 4 weeks after two vaccines. Failure to generate antibodies is found at higher proportion in some specific patient sub-groups; in particular, in patients with ANCA-Associated Vasculitis who have received Rituximab treatment. 

Looking in detail at patient vaccine response within each of the disease subgroups included in the study, researchers found that a significant proportion of patients studied as part of OCTAVE generate lower levels of SARS-CoV-2 antibody reactivity, when compared with healthy subjects after two SARS-CoV-2 vaccines. 

The proportion of patients with lower levels of antibody reactivity as per disease cohort compared to the baseline for healthy subjects: 

• Those with Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis (AAV) (a group of diseases characterised by destruction and inflammation of small vessels) who are being treated with Rituximab – 90%
• Those with inflammatory arthritis – 54%
• Those undergoing Haemodialysis (the most common kind of dialysis, a procedure to remove waste products and excess fluid from the blood when kidneys stop working properly) – 21%
• Those on Haemodialysis receiving immunosuppressive therapy – 42%
• Those with Hepatic (liver) disease – 51%
• Those with solid cancer – 17%
• Those with Haematological malignancies (blood cancers) – 39%
• Those who have have undergone haemopoietic stem cell transplant (bone marrow transplant) – 33%

Importantly, however, the significance of these findings in terms of what they can tell us about vaccine protection from exposure to COVID-19 is not currently known, as there is no current agreed clinical cut off to measure COVID-19 vaccination response. 

The OCTAVE study looks at those with immune mediated inflammatory diseases including rheumatoid arthritis, psoriatic arthritis, ANCA-Associated Vasculitis, inflammatory bowel disease, as well as hepatic disease and renal failure. So far more than 2,500 patients have been recruited to the trial making it one of the largest global studies in which detailed immune response is being assessed post-SARS-CoV-2 vaccination. 

The data reported, published as a pre-print today on The Lancet’s Pre-print Server and therefore not yet subject to peer review, includes the post-vaccine immune response results from the first 600 patients recruited 4 weeks post second dose in the OCTAVE study. As the study progresses, around 3,000 people will be recruited. Participants in the study have all received either COVID-19 mRNA Vaccine BNT162b2 (Pfizer/BioNTech) or ChAdOx1 Vaccine (AstraZeneca) as part of the National COVID19 vaccination programme.