INFORM and EPOCH Studies Unveil COVID-19's Heavy Toll on Immunocompromised Individuals

The young woman with a medical mask on her face stands on the crowded street.

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In 2 extensive studies, INFORM (INvestigation oF cOvid-19 Risk among iMmunocompromised populations) and EPOCH (Emerging Populations and Outcomes associated with COVID-19-Health Conditions in the United States), on 2 continents, investigators examined the impact of COVID-19 on immunocompromised individuals. Despite vaccination, immunosuppressed patients faced a significantly higher risk of hospitalization and severe outcomes, with certain groups at even greater risk, including solid organ transplant recipients and blood cancer patients. These findings underscore the need for tailored strategies to protect this vulnerable population.

“INFORM is an observational, population-based, retrospective cohort study among nearly 12 million people aged 12 years and older in England to assess clinical outcomes and utilization of healthcare resources due to COVID-19,” according to the press release. “EPOCH provides robust real-world data on COVID-19 risks and outcomes in IC and non-IC populations in the US, conducted using an extensive insurance claims database of nearly 17 million individuals.

To find out more, Infection Control Today^® (ICT^®) spoke with Paul Moss, OBE, PhD, MBBS, FRCPath, FMedSci, Institute of Immunology and Immunotherapy, deputy head of college and medical and dental sciences and professor of hematology, University of Birmingham, UK, and INFORM investigator. The INFORM and EPOCH studies were published in Lancet Regional Health Europe and Current Medical Research and Opinion, respectively. Data from INFORM are also being presented at the 12th Annual IDWeek 2023 Conference in Boston, Massachusetts, from October 11 to 15.

ICT: What are the key findings of the INFORM and the EPOCH studies regarding the impact of COVID-19 on immunocompromised individuals?

 
Paul Moss, OBE, PhD, MBBS, FRCPath, FMedSci: Thank you for asking and for showing interest. There were 2 studies here [that are] complementary [to each other] from different countries. We all know that when the pandemic started, all adults were at risk of COVID-19, and the focus was on protection for the general population. Obviously, vaccinations came through that. As time has moved on, we've now started to understand a little bit more about the patient groups that are most at risk, as well as the [older population]. It is patients with immune suppression who are at much more increased risk, and these are what these 2 studies addressed in slightly different ways—the risk for patients with immune suppression of COVID-19 and poor outcomes.

ICT: Would you give me a little of the key findings of those 2 studies?

PM: Let me talk to start with the INFORM study. This was based in the UK, and both studies were using patient electronic record systems, which is a huge advantage that we have these days. This was a UK study, and it looked at around a quarter of the UK population and assessed people over a period of around 5 years for their status of immune suppression.

Broadly, that's around 4% of the population. And then, [the electronic record system] tracked those people in relation to their COVID-19 infections, particularly hospitalizations, intensive care unit admissions, and deaths in the first year of Omicron. So, over a period of 12 months, and the key findings were although immune-suppressed patients were roughly 4% of the population, they accounted for a quarter of all hospitalizations, 22% to 28% of ICU admissions, and 25% of deaths. And so they're on average around 14-fold or greater risk of hospitalization.

This is despite over 80% of these patients having at least 3 vaccines. The key finding here [is that] they remain at relatively greatly increased risk despite vaccines and booster vaccines.

 
 
ICT: Do you know how long after their vaccines they contracted COVID-19 because that would matter.

PM: It would be difficult to focus down on that much detail, to be honest. The study’s data included people who'd had at least 1 booster, but time after a vaccine wasn't addressed.

You're absolutely right. There is obviously some vaccine waning in terms of immunogenicity and clinical protection. I suppose you would expect that to be potentially, to some extent, similar in the immune suppressed and the control populations, but that's something that could be looked at in further analysis.

 
ICT: How do the COVID-19 outcomes in immunocompromised individuals compare to the general population as revealed by the studies?

PM: I mean a hugely increased risk, and I think the other advantage of the informed study—because it's such a large data set of around 12 million people—is it can start to address the type of immune suppression that places people at the greatest risk. And this was quite interesting: it was particularly those patients who've had a solid organ transplant, kidney transplant, liver transplant, and hematological patients, particularly those on treatment.

They have had a recent stem cell transplantation, and I think it's just such a beautiful example of using very large patient datasets to try and drill down into--not entirely individual patient risk--but patient group risk. For the future, it's the question [of] how we can better protect these groups of patients.

 
ICT: Do you have any ideas on how to protect these patients at risk?

PM: It's clear that vaccines have transformed the COVID-19 pandemic. They are the cornerstone of protection, but for patients with immune suppression, those with primary and secondary immune deficiencies. Of course, a vaccine needs a competent immune response, and if the patient can't make an immune response, then they're still at risk. This is where things such as passive protection through injection of therapeutic monoclonal antibodies should be provided strong protection, and that's been shown in a lot of meta-analyses. That's one very important direction for this group of patients. And the ability to generate these therapeutic monoclonals quite quickly to address the recent vaccine variants.

ICT: What are the potential implications of these findings for health care systems and public health strategies, especially in the context of rising COVID-19 cases? I assume that you're having the same rise that we are here in the United States.

PM: Yeah, COVID-19 has become a chronic endemic problem of infection, hasn't it? Within the population, influenza remains remarkably seasonal. We don't quite know what COVID-19 pattern [it] will settle down into, but we're having repeated waves. The overall absolute levels of morbidity and mortality are down, but what this study shows is that relative risks are massively increased in this immune-suppressed population. For public health, [the question is] how do we better allocate and identify individual risks and patient group risks and then apply the appropriate prophylactic measures to give that protection? Having these 2 studies from major health care systems provides a lot of that information now.

  
ICT: How does the EPOCH study contribute to our understanding of the burden of COVID-19? 

PM: The EPOCH study was a slightly different study. This was done in America. [It] didn't really address cap vaccination-related protection. It was really looking at the actual clinical burden and of course, financial burden and all health care systems; now we have to take a financial view of the best care. And it was looking at the clinical. Requirements of patients with immune suppression when they got COVID-19 and got a severe infection, and this was using a huge population based around 16 and actually was 23 million people using the American HIRD [Healthcare Integrated Research Database] system, and it showed the financial impact of COVID-19 infection. That's very relevant in terms of understanding the potential costs of prophylactic therapies, which, of course, have to be balanced against how much health care costs they can potentially prevent.

 
ICT: Yes, but they also prevent deaths and long COVID, or we'd like to think long COVID too. Emotionally, we should not put a price on preventing people from getting sick.

PB: Well, you know, I think you're right. The finance, we have to talk about it. But you're right, psychologically, I didn't talk about [that]. That's very important.

I was in the clinic this afternoon with the patient who's coming in wearing a mask. The wife said that they're [tired], got immunodeficiency, by the way, and saying, “We don't really go on holiday anymore. Can we go out?” and I'm, you know. [Shrugs]. The psychological burden of this shielding or protecting people and patients from society is enormous. And that's something that has to be taken into account as well.

 
ICT: What specifically surprised you about the findings of these studies?

PM: I think the relative risk surprised me, actually. I mean, measuring immune suppression is quite a continuous variable. It's almost like measuring…which level of blood pressure is bad. So, how you define immune suppression can be debated, but this was quite stringent. It was 4% of the population.

That's quite [a lot], but it’s still a minority, although reasonable, but to consider that they are representing over 20% to 28% of all intensive care admissions and so forth was surprising. Then, because you've got such a large data set, you can look at the type of infections that are proving to be putting patients at the greatest risk. That's when you start to see these interesting patterns with the power of INFORM. I think to me it was how important solid organ transplantation is as a risk factor and also blood cancer.

I'm a blood cancer doctor, and it's notable how much patients with blood cancer are at greater risk than patients with more solid and more common solid tumors such as lung, breast, and colon cancer. So, there's something about blood cancers that is particularly immune suppressive, and that's something we need to keep an eye on.