The risk of severe illness and death from COVID-19 among certain sub-groups of the most clinically high-risk patients remained high, despite vaccination, new analysis has found.
New results from the landmark OCTAVE (Observational Cohort Trial-T-cells Antibodies and Vaccine Efficacy in SARS-CoV-2) study show the real-world vaccine responses and infection outcomes in clinically at-risk patients with a range of immunocompromised or immunosuppressed conditions.
Preliminary data in August 2021 showed a significant proportion of clinically at-risk patients had a low, or undetectable, immune response after two doses of the same SARS-CoV-2 vaccine.
The research team from a consortium of leading UK institutions – including the Universities of Glasgow, Birmingham, and Oxford – have now published the real-world infection outcomes for this clinically at-risk group.
The study covered 2021 to mid-2022, and included patients infected with the alpha, delta and omicron strains of SARS-CoV-2. The data does not estimate the impact of third and fourth vaccinations.
The researchers found, while in most at-risk patient groups the overall COVID-19 infection rates were low, the risk of severity and death was high among people with a sub-group of conditions, despite vaccination.
This was particularly the case during the delta wave. While omicron, which is 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.
OCTAVE enrolled 2,686 patients, all with reduced immune function, from 20 hospital sites across the UK. These included patients receiving immune-suppressive therapy for haematological malignancy, patients receiving haematopoietic stem cell transplants, or patients treated with CAR-T cell therapy.
Out of the whole patient cohort, 474 patients caught COVID-19 up to one year after the date of their first vaccination – with one having the alpha variant, 110 having the delta and 336 having omicron.
Out of those patients who had the virus, 48 were admitted to hospital and 15 people died from the disease.
Three quarters of infections occurred more than six months after the second vaccination and were in patients with a kidney transplant, inflammatory arthritis and Crohn’s Disease.
Infections occurring within six months of the second vaccination were not more severe than those reported six months or longer post second vaccination.
About 90% of infections were mild and there were some asymptomatic cases. The severe cases that ended up in hospitalisation or death was reported in 9.8% of infections and occurred predominantly in patients with renal disease.
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 CAR-T cell treated patients.
Professor Iain McInnes, lead of the OCTAVE trial, 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.”
Professor Andrew Ustianowski, NIHR clinical lead for the COVID-19 vaccination programme and joint national infection specialty lead, added: “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."
The OCTAVE trial is one of the largest studies in the world 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.
Barnes E, Goodyear CS, Willicombe M, Gaskell C, Siebert S, I de Silva T, Murray SM, Rea D, Snowden JA, Carroll M, Pirrie S, Bowden SJ, Dunachie SJ, Richter A, Lim Z, Satsangi J, Cook G, Pope A, Hughes A, Harrison M, Lim SH, Miller P, Klenerman P, PITCH consortium; Basu N, Gilmour A, Irwin S, Meacham G, Marjot T, Dimitriadis S, Kelleher P, Prendecki M, Clarke C, Mortimer P, McIntyre S, Selby R, Meardon N, Nguyen D, Tipton T, Longet S, Laidlaw S, Orchard K, Ireland G, CONSENSUS; Thomas D, Kearns P, Kirkham A, McInnes IB, OCTAVE Collaborative Group. (2023) “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.” Nature Medicine, doi: 10.1038/s41591-023-02414-4
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