Early data from an ongoing UK study investigating COVID-19 vaccine responses in immunocompromised subjects indicates up to 60 percent of this cohort have effective immune responses to current vaccines. As well as identifying those patient sub-groups most at-risk of sub-optimal vaccine responses, the research is looking at the efficacy of booster doses in immunocompromised patients.
As vaccine clinical trials generally recruit healthy adult populations they cannot offer insights into how at-risk populations may respond. Over the last few months a growing body of evidence has started to accumulate suggesting those with weakened immune systems may not respond effectively to COVID-19 vaccines.
This data has led to several countries beginning third-dose booster programs for immunocompromised populations. However, detailed immunological studies in these patient groups is limited.
Early in 2021, as COVID-19 vaccines began being administered widely in general populations, a large study commenced looking at responses in immunocompromised patients. Called OCTAVE (Observational Cohort Trial T cells Antibodies and Vaccine Efficacy in SARS-CoV-2) the study plans to enroll over 3,000 subjects in a variety of immunocompromised sub-groups, including patients with end-stage kidney or liver disease, those with gastrointestinal disease on immune suppressive therapy, vasculitis, rheumatoid arthritis, cancer, and patients undergoing stem-cell transplants.
“The roll-out of the vaccine programme was extremely important for these vulnerable groups of patients, however due to their underlying medical conditions and treatments, which can weaken their immune systems, we were concerned that people with these medical conditions may not receive optimal protection, so it was, and remains, extremely important to investigate this unanswered question,” explains Iain McInnes, who is leading the OCTAVE study.
Preliminary data from the OCTAVE study has been now published on The Lancet’s pre-print server. The results, yet to be peer-reviewed and formally published, comprise the first 655 subjects in the study.
Looking at serological immune responses the research found 40 percent of the entire cohort generated sub-standard antibody responses to two doses of COVID-19 vaccine, compared to an average response in healthy adults. Approximately 11 percent of all patients in the study failed to generate any antibodies at all in a four-week period following two vaccine doses.
A striking 90 percent of patients with ANCA-associated vasculitis responded poorly to COVID-19 vaccines. This cohort were mostly being treated with a drug called rituximab, which is a targeted immune B cell depletion drug.
Other low-responding patient cohorts included 54 percent of patients with inflammatory arthritis and 51 percent of patients with hepatic disease. At the other end of the spectrum, only 17 percent of patients with solid cancers and 21 percent of patients on haemodialysis showed sub-optimal responses to COVID-19 vaccines.
“On the whole, and as predicted, people who are taking drugs to suppress their B cells (which are the cells that make the antibodies) responded least well,” says Eleanor Riley, an infectious disease researcher from the University of Edinburgh who is not working on the OCTAVE study. “However, some other potentially 'at risk' groups actually responded quite well, meaning they are not as 'at risk' as we might have feared. This information will be very useful to clinicians in advising their patients.”
The OCTAVE study is ongoing, and is expanding to include investigations into how these vulnerable patient populations respond to booster doses currently being rolled out in the UK. McInnes says it is good news 60 percent of subjects studied so far are responding well to COVID-19 vaccination.
“While 40 percent of these clinically at-risk patent groups were found to have a low or undetectable immune response after a double dose of the vaccine, we are encouraged that this figure isn’t higher,” says McInnes. “However, it is possible even partial protection may be clinically beneficial, and this is something we will closely monitor.”
The new research has been published on The Lancet’s preprint server.