For people with normal immune systems, the 'post-pandemic era' means relief—the inconvenience of infection, lockdowns, and masks has gradually faded from daily life. However, for immunocompromised individuals, COVID-19 is far from an inconvenience; it remains a persistent threat.

Although vaccines have helped humanity emerge from the pandemic's difficulties, according to a report by pharmaceutical giant AstraZeneca,reportimmunocompromised individuals often fail to gain adequate protection from vaccines. Even after multiple doses, more than 10% of immunocompromised people—including cancer patients, organ transplant recipients, and those taking immunosuppressants—cannot produce the antibodies needed to fend off infection.

To gain deeper insight into the burden of COVID-19 on immunocompromised patients, AstraZeneca conducted two real-world studies, using millions of health records to assess the size of the immunocompromised population in the UK and US, as well as the risks these patients face during the transition of the pandemic to an endemic phase.

Dr. Paul Moss, Deputy Dean of the College of Medical and Dental Sciences and Professor of Haematology at the University of Birmingham, UK, is an investigator on the UK study (named Inform). For his contributions to immunology and COVID-19 research, Moss was awarded an OBE in the 2022 Queen's Birthday Honours.

"The Inform study is based on UK electronic patient records, covering about 25% of the English population—nearly 12 million people," Moss said. "This gives the study enormous statistical power and identified that the immunosuppressed population accounts for about 4%." Although immunocompromised individuals make up about 4% of the population, they accounted for 22% of all COVID-19 hospitalizations, 28% of COVID-19 ICU admissions, and 24% of COVID-19 deaths in 2022, Moss said.

"One of the lessons learned over the past three years is how to optimize immune protection for patients across all fields of clinical medicine."

During the pandemic, AstraZeneca developed Evusheld, a preventive injectable antibody, as a pre-exposure prophylaxis alternative for immunocompromised individuals. Although these options provided viable choices for patients, Evusheld's efficacy against newer viral strains declined, prompting regulators such as the FDA torevoke its emergency use authorization。

Other companies, such as Invivyd, are aiming to fill the gap in the monoclonal antibody market for immunocompromised COVID-19 patients.gapThis summer, the company met with the FDA and established a path for itsclinical-stage monoclonal antibody candidateto receive emergency authorization.

Here, Moss discusses the results of AstraZeneca's large-scale data study and why healthcare systems must remain vigilant in protecting vulnerable populations even as the pandemic subsides.

This interview has been edited for length and style.

PHARMAVOICE: Why is it important to study the burden of COVID-19 on immunocompromised populations?

Dr. Paul Moss:At the beginning of the pandemic, everyone was at risk, so the entire general population needed protection through vaccines, which has fortunately been achieved. But over time, we began to recognize that certain groups—particularly the very elderly and the immunosuppressed—are at higher risk of infection and severe complications. The Inform study provides a new perspective to examine this issue and define the absolute risk for each patient group.

Currently, what preventive treatments are available for immunocompromised patients who cannot gain protection from vaccines?

This is an important question. Identifying high-risk groups is crucial because we can inform them of their immunosuppressed status, which will affect their behavior—the identification of relative risk is important for how patients manage their lives. Vaccination must be optimized, providing additional doses for many of these groups. For patients who cannot mount an appropriate response to vaccines, we must consider other approaches—especially in the early stages of the COVID-19 pandemic, preventive injectable monoclonal antibodies provided strong protection.

Has this type of work received enough attention? Why did it take three years to learn such an important lesson?

We have all come to understand the importance of immunosuppression more deeply from the COVID-19 pandemic. One of the lessons learned over the past three years is how to optimize immune protection for patients across all fields of clinical medicine. Given the vast amount of information we now have about the susceptibility of various patient groups, we can build on this to grade immunosuppression status—similar to how we grade other medical indicators like blood pressure—and provide patients with risk scores to guide their medical care.

Now that you understand the size and hospitalization rates of immunocompromised patients, what do you want to learn next?

Because of the large scale of the Inform study, we can delve into quite fine detail, and there have been some unexpected findings in the study. For example, solid organ transplant patients have the highest relative risk, at about 13-fold. The susceptibility of blood cancer patients is also particularly surprising. We hope to provide patients with personalized individual risk and use all appropriate therapies more targeted. This drives us to understand why certain diseases are so immunosuppressive and may change treatment approaches to reduce immunosuppression.

Given the political environment surrounding COVID-19 and the pandemic, can this type of research influence policy?

I think it can. In the UK, early in the pandemic, we were able to use emerging medical record data to prioritize antiviral therapies and preventive monoclonal antibody treatments for immunosuppressed patient groups. This is an excellent example of rapidly translating medical record data into public health decisions, which are, of course, key to changing clinical outcomes.

How much of the work you've done here can help the world prepare for the next pandemic?

We have been told that some pandemic is inevitably going to occur in the future, and we have learned a lot from this one. I think we will increasingly focus on the optimal protection of immunosuppressed populations, and we have developed new therapies—preventive injectable antibodies are potential game-changers because they have long-lasting effects and can overcome the problem of patients not responding to vaccines. We are likely to see these drugs deployed rapidly to address a wide range of infectious pathogens.

Where will you take this research next?

This study covers 25% of the UK population, and I think we should try to expand it to the entire population, perhaps conducting similar studies in other countries. Defining individual risk is one way to help us understand the underlying mechanisms of immunosuppression and develop the most effective therapies to reduce morbidity and mortality.