Two in five people with an impaired immune system have a “low or undetectable” antibody response after receiving two doses of a COVID-19 vaccine, according to new research.

The figure comes from the OCTAVE study, which was created to address the gap in knowledge left by the lack of chronically ill and immunocompromised people in vaccine trials.

The study is still running and researchers aim to gather data on around 3,000 immunocompromised people, including those with cancer, kidney disease, liver disease, inflammatory arthritis, inflammatory bowel diseases, and vasculitis.

Researchers from the universities of Glasgow and Birmingham compared the immune responses between 600 patients with immune-mediated inflammatory diseases and 231 healthy people after they had received both doses of either the AstraZeneca or Pfizer vaccines.

Around three in five people from the vulnerable group had an antibody response similar to that of healthy adults but the others had antibody responses that were lower.

Some 11% failed to generate any antibodies four weeks after receiving the second vaccination, with the researchers saying that almost all of these people had vasculitis, a group of rare diseases which lead to inflammation of the blood vessels.

Antibodies are not the only part of the human body’s fight against COVID-19, however.

T cells, a particular form of white blood cell, are the master controllers of the immune system and the study showed T cell response in almost all patient groups was similar to healthy adults.

Even among those who had shown undetectable antibody levels, there was a good T cell response, indicating that at least some form of immunological response had been mounted.

It is not clear what this means for how strong the vaccine’s protection is for these people – although we know that there is a link between higher levels of antibodies and neutralisation of COVID-19, we do not know what levels are needed for protection against the virus.

Co-investigator Prof Carl Goodyear said: “When we look at the T cell responses across all the cohort, they look identical to the healthy controls, so there was a robust T cell response being generated.

“The vaccine is actually immunologically active in all patients, they can mount an immunological response.

“It’s the type of response to the quality of the response we’re really trying to understand here.”

The news comes as data from the Office for National Statistics show that there were 571 deaths in England and Wales in the week ending 13 August where COVID-19 was mentioned on the death certificate – up 8% on the previous week and the highest number since March.

Experts are expected to make a recommendation on whether booster jabs should be given to vulnerable groups during the autumn, ahead of what is expected to be a difficult winter.

Trial lead, professor Iain McInnes, from the University of Glasgow, said: “Our data suggests that a booster for people who have mounted either an absent or lower level of antibody response would be a very reasonable next step.

“Our view as a group of investigators is that the third inoculation would indeed be a reasonable approach, but we are only one part of the data set that will inform wider policy.”

Describing the absence of antibody response among some immunocompromised patients as “probably not ideal”, he added that the “large majority” of people in these groups were “probably going to be fine”, although “more work is required to be absolutely reassured”.

Professor Charles Swanton, Cancer Research UK’s chief clinician, said the study “reflects the evidence we’ve seen so far and includes only a small number of cancer patients, with a limited number of cancer types”.

“Overall, the majority of cancer patients had an immune response to the vaccine, even if levels of antibodies were lower in some cases than healthy controls, but the study didn’t look at how this response translates to COVID-19 protection.

“We urgently need data across blood and solid tumour cancer types to understand which groups are most at risk from vaccine breakthrough infections.”

He encouraged cancer patients to get vaccinated if they can and to follow the advice of their doctor.

The study has been published as a pre-print by The Lancet.

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