For people with active immune systems, the phrase “post-COVID” comes as a relief — the inconveniences of infection, lockdown and masked encounters have largely slipped into the background. For the immunocompromised, the coronavirus is more than an inconvenience. It is a constant threat.
Although vaccines helped humanity dig itself out of the pandemic hole, immunocompromised people are often not well protected by the shots, according to a report from pharma giant AstraZeneca. Even when vaccinated multiple times, more than 10% of immunocompromised people — including cancer patients, organ transplant recipients and those taking immunosuppressive medicines — are unable to produce the antibodies needed to fight off infection.
To learn more about the burden of COVID-19 on immunocompromised patients, AstraZeneca ran two real-world studies to assess the volume of immunocompromised patients in the U.K. and U.S. through millions of health records and the risk faced by these patients as the pandemic began to transition to the endemic stage.
Dr. Paul Moss, deputy head of the College of Medical and Dental Sciences and Professor of Haematology at the University of Birmingham in the U.K., was an investigator in the U.K. study, titled Inform. For his work in immunology and COVID-19 research, Moss was awarded the Order of the British Empire in the 2022 Queen’s Birthday Honours.
“Inform was a study of electronic patient records in the U.K. that covered around 25% of the English population — nearly 12 million people,” Moss said. “That gave it tremendous statistical power, and identified that the population who were immunosuppressed was nearly 4%.”
Although immunocompromised people made up about 4% of the population, they represented 22% of all COVID hospitalizations, 28% of ICU admissions due to COVID and 24% of all COVID deaths in 2022, Moss said.
"One of the lessons that will be learned from the last three years is how we optimize immune protection for patients and all aspects of clinical medicine."
Dr. Paul Moss
Deputy head of the College of Medical and Dental Sciences and Professor of Haematology at the University of Birmingham
AstraZeneca developed Evusheld, a prophylactic injectable antibody, during the pandemic as a pre-exposure alternative to vaccines for people who are immunocompromised. And although these presented a viable option for these patients, Evusheld has shown less efficacy against newer strains of the virus, prompting regulatory agencies like the FDA to pull authorization.
Other companies, such as Invivyd, are gunning to fill the void of monoclonal antibodies on the COVID market for immunocompromised patients. This summer, the company met with the FDA and nailed down a path to winning an emergency authorization for its clinical-stage mAb candidate.
Here, Moss discusses the results of AstraZeneca’s massive data studies and why it’s so important for healthcare systems to stay vigilant in protecting vulnerable populations, even as this particular pandemic subsides.
This interview has been edited for brevity and style.
PHARMAVOICE: Why is it important to study the burden of the COVID pandemic on immunocompromised people?
DR. PAUL MOSS: In the early days of the pandemic,everybody was at risk. And so a whole general population needed to get protection that was delivered, thankfully, through vaccines. But as time moved on, we’ve started to recognize there are certain groups, particularly the very elderly and the immune suppressed, who are at higher risk of infection and serious complications from that infection. The Inform study provided a new way to look at this problem and define the absolute risk for individual patient groups.
What preventative treatments are currently available for the immunocompromised patients who aren’t protected by vaccines?
It’s an important question. It’s important to recognize the high-risk groups because we can inform them of their immune-suppressed status, and that will influence behavior — the identification of relative risk is important for how patients manage their life. And vaccination has to be optimized to give additional doses to many of these groups.
For those who are unable to respond appropriately to vaccination, we have to look at other methods — particularly in the early stages of the COVID-19 pandemic, a prophylactic injectable monoclonal antibody provided strong protection.
Is there enough priority being placed on this type of work? Why has it taken three years to learn such an important lesson?
We all recognized the importance of immune suppression much more strongly from the COVID-19 pandemic. One of the lessons that will be learned from the last three years is how we optimize immune protection for patients and all aspects of clinical medicine. Given the huge amount of information we have now on susceptibility of individual patient groups, we can use them as a basis to perhaps grade immune suppression status — a bit like we grade other medicine like blood pressure and so forth — and provide risk scores for patients to guide their medical care.
Now that you understand the scale of immunocompromised patients and hospitalization, what’s the next thing you want to understand about this?
Because of the scale of the Inform study, you get down to quite sophisticated detail, and there were a few surprises in the study.
The highest relative-risk patients were those who had solid organ transplants, for instance, to about 13-fold. The susceptibility of patients with blood cancers has been a particular surprise, as well. It would be lovely to be able to give a personalized individual risk for patients and use all of the appropriate therapies in a much more targeted way. It’s giving us impetus to understand why some of these conditions are so immune suppressive and perhaps to change the nature of treatments to reduce that immune suppression.
With the political landscape surrounding COVID and the pandemic, could a study like this have an impact on policy?
I think so. In the U.K., in the earlier days of the pandemic, we were able to use emerging healthcare record data to prioritize immune suppressed patient groups for antiviral therapies and prophylactic monoclonal antibody therapy. It was a lovely example of taking healthcare record data quite rapidly into public health decision making, which of course is the priority for changing clinical outcomes.
How much of what you’re doing here could help the world prepare for the next pandemic?
We are told there will inevitably be some sort of next pandemic, and we’ve learned an awful lot during this one. I think we will now be increasingly focused on optimal protection of immune suppressed populations, and we have developed new therapies — prophylactic injectable antibodies are potential game changers because they are very long lasting and can overcome the effect of patients who don’t respond to vaccines. We may well see those agents deployed quite rapidly to target a wide range of infectious agents.
Where do you take this next?
This was 25% of the U.K. population, and I think we should try and extend it to the whole population, and perhaps similar studies in other countries. Defining individual risk is one way we can help to understand the underlying mechanisms of immune suppression to develop the most effective treatments to reduce morbidity and mortality here.
