Protecting the immunocompromised: Preventative measures against COVID-19

COVID-19 vaccines are not as effective in immunocompromised individuals as they are in the general population, due to an inability to produce a robust protective response to the vaccine. The same goes for other vaccines, too. As a result, in terms of the coronavirus, immunocompromised individuals can be insufficiently protected and remain at high risk for SARS-CoV-2 infection and serious outcomes from that.

Two large, real-world evidence (RWE) studies from AstraZeneca - INFORM and EPOCH, with data covering almost 30 million individuals - have shown that approximately 25% of all COVID-19 hospitalisations, ICU admissions, and deaths are comprised of the immunocompromised – underscoring the continued need for preventative options for people insufficiently protected by vaccination alone.

The INFORM and EPOCH studies were published in Lancet Regional Health Europe and Current Medical Research and Opinion respectively. INFORM was an observational, population-based, retrospective cohort study among nearly 12 million people aged 12 years and older in England to assess clinical outcomes and utilisation of healthcare resources due to COVID-19. Meanwhile, EPOCH provides robust real-world data on COVID-19 risks and outcomes in immunocompromised (IC) and non-IC populations in the US, conducted using an extensive insurance claims database of nearly 17 million individuals.

Back in the autumn, pharmaphorum spoke with Dr Paul Moss of the Institute of Immunology and Immunotherapy, deputy head of the College of Medical and Dental Sciences, Professor of Haematology at the University of Birmingham, UK, and INFORM study investigator, about the disproportionate burden of COVID-19 on those who are immunocompromised. As the coronavirus variants continue to do the rounds this winter, the conversation is all too pertinent.

For the immunocompromised, vaccines are not enough

What COVID-19 really brought into focus was the “burden of infection”.

“To date, our understanding of the burden of COVID-19 in the immunocompromised population has been limited due to a lack of dedicated research in this area,” said Dr Moss. “INFORM and EPOCH are the first large-scale studies that jointly provide detailed insight into the impact that COVID-19 continues to have on those patient groups across different geographies. As our data shows, vaccination alone is often not enough to protect these individuals from potential devastating consequences of COVID-19 and effective prevention strategies are needed for this population. We must work together to find solutions, so that this vulnerable population can move on from the pandemic.”

“Quite early, we realised that the elderly were particularly at risk, but over time the focus has really started to increase on the most vulnerable […] including the elderly and also particularly immune-suppressed patients,” he explained. “And so, I think there's a great need now to improve on knowledge and understanding of that risk and the INFORM study is a very interesting piece of work.

It's firstly dramatic in its scale because it looked at the healthcare records of about 12 million people.”

For reference, that’s roughly a quarter of the UK population.

“[INFORM] identified people who were immune-suppressed, according to a range of criteria, and then it linked that to COVID hospitalisations during 2022,” he continued. “That's a very good year to choose because that was a whole 12 months of Omicron COVID, which is the virus variant that we're now dealing with anyway [in October].”

The INFORM (INvestigation oF cOvid-19 Risk among iMmunocompromised populations) study was an observational, retrospective cohort study to describe clinical outcomes and utilisation of healthcare resources among individuals with COVID-19 in England during Omicron (January-December 2022), as the pandemic began to transition to an endemic phase. It found that the immune-suppressed population is around 3.9% of the general population of adults, but it made up 22% of all COVID 19 hospitalisations, 28% of ICU admissions or intensive care units for COVID, and 24% of COVID deaths.

“You can see that dramatic increase in relative risk from severe COVID that remains for immune-suppressed patients,” Dr Moss said. “Remarkably, this is despite at least three vaccine doses. So, it's showing that, although vaccines have reduced the overall absolute risk dramatically across the population, relative risk remains much higher for these immune-suppressed patients.”

Indeed, even after repeated doses of COVID-19 vaccines, IC individuals have been shown to have up to a 14 times greater risk of COVID-19 hospitalisation compared to the general population.

“That’s why we have to look at other opportunities to protect this population,” Dr Moss continued. “Potentially for people who can't respond appropriately or optimally to vaccines […] Things such as long-acting, monoclonal antibody injections, which were very effective in the early days of the pandemic.”

Each at-risk group has its own challenges

Of course, not every person is alike, and immune-suppressed people fall into vastly different categories of risk, including those with a compromised immune system from having received solid organ or stem cell transplants, or those who are undergoing treatment for blood cancers.

“People who've had a kidney transplant or liver transplant - after that transplantation patients have to take immune-suppressing medication, but the relative risk here was around 13% overall,” Dr Moss explained. “Then, patients with haematological malignancies, blood cancers - the relative risk is particularly high and that's one thing we've noticed during COVID, that a patient with blood cancer is much more immune-suppressed than a patient with solid tumours, such as cancer of the colon or breast, and so we're trying to understand that and I think one of the impetuses from this study is to understand the mechanisms of immune suppression in these different individuals.”

A health burden, and a financial burden, too

The US-based EPOCH study, by contrast, looked at the financial health economic case.

EPOCH (Emerging Populations and Outcomes associated with COVID-19-Health Conditions in the United States) was a retrospective, observational cohort study evaluating the burden of illness and healthcare resource utilisation conducted among US commercially insured patients in the Healthcare Integrated Research Database (HIRD) of nearly 23 million people. Data was anonymised and HIPPA compliant and the study period took place across three years: between 1 April 2018 and 31 March 2022, with infections analysed from 1 April 2020 to 31 March 2022.

EPOCH did not take account of vaccination status, but the financial burden of immune-suppression and severe COVID-19 infection, and the psychological burden of that, also, when it comes to the clinical need to protect people and the optimal use of resources for that.

“[Epoch] looked at the financial cost of severe COVID in the US population and defined that it was really very sizable, and it used very, very large healthcare records over 10s of millions of people,” Dr Moss explained. “So, a complementary but really quite different study, and it was useful for when we consider that some of the protective measures we might consider will of course have a financial burden. But, overall, they're likely to more than outweigh the cost of doing nothing.”

Proving the importance of personal and pharmacological interventions

And what purpose these studies?

“This data from electronic healthcare records, because of its scale and power, can translate potentially quite quickly into public health interventions,” Dr Moss said. “During COVID, groups were established to identify patients at the greatest risk in terms of prioritising them for things like COVID antiviral treatments and monoclonal antibody prophylactic treatments.”

“I think what the INFORM study does is it takes us a step further to understanding the granularity of the relative risk of these individual patient groups,” he continued. “It's important for patients and clinical teams to understand relative risks so that they can take the appropriate personal and pharmacological interventions.”

“It’s now imperative that we use this information to provide the optimal immune-protective strategies for this group beyond vaccination,” Dr Moss concluded.