Risk of Severe COVID-19 Infection in Pediatric Patients With MS on B-Cell-Depleting Therapies

Teri Schreiner, MD

Immunosuppressants are commonly used to treat pediatric patients with multiple sclerosis (MS) and related disorders such as clinically isolated syndrome (CIS), myelin oligodendrocyte glycoprotein antibody disorder (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD). Therefore, understanding the effect of COVID-19 infection in patients with these conditions may inform treatment decisions with immunosuppressants.¹

In a recently published study, investigators characterized COVID-19 infection prevalence and severity among a cohort of pediatric patients with MS and related disorders, as well as the effect of disease-modifying therapies. Findings showed that B-cell-depleting treatment was associated with a higher risk of COVID-19, higher rates of hospitalization, and ICU admission, suggesting the therapy may carry a higher risk of severe infection in pediatric patients with MS and related disorders.

Teri Schreiner, MD, lead author of the study, recently sat down with NeurologyLive® in an interview to discuss the objective and methodology used to characterize pediatric patients with MS and related disorders infected with COVID-19. Schreiner, pediatric neuroimmunologist and associate professor at the University of Colorado and Children's Hospital Colorado, also spoke about the main findings and significant key points from the study. In addition, she talked about the results impact treatment decisions and preventative approaches for pediatric patients with MS who contract COVID-19.

NeurologyLive®: What was the objective and methodology for the characterization of pediatric patients with MS and related disorders infected with COVID-19?

Teri Schreiner, MD: This study leveraged a preexisting database that had been set up by the network of pediatric MS centers. It was prospectively enrolling a database of patients who are less than 18 when they're diagnosed with pediatric MS, and related disorders. Those related disorders include MOGAD, NMOSD, acute disseminated encephalomyelitis (ADEM), CIS, and sometimes, demyelinating disease not otherwise specified. So, at the beginning of the pandemic, we leveraged this preexisting system and asked additional questions during standard of care visits to better understand the risk of COVID-19 infection among this population. The study was done during standard of care visits in which additional questionnaires were filled out and data was collected. At the end of this time period, we took a look and tried to understand what was the risk of COVID among this population of MS, and related disorders in pediatric patients.

What are the main findings and the key points that were significant from the study?

One of the things that I think this study is notable for is the relatively large size for rare disorders. We had 669 patients and among these, there were 73 COVID-19 infections. Additionally, among that subset of patients who had COVID-19 and were hospitalized, 8 of the 9 of them were on a B-cell-depleting therapy to treat their multiple sclerosis. Furthermore, of the 9 who were hospitalized, 5 required ICU level care, and all 5 of those patients were on B cell depleting therapy as well. When we did further analysis, logistic regression, to try and identify or quantify rather the odds of being hospitalized among patients on B cell depleting therapy with COVID-19, the odds ratio was 15 times higher for those on B cell therapy to be hospitalized with a COVID-19 infection.

How might these results impact treatment decisions for these patients who have contracted COVID 19 and preventative approaches to not getting infected?

This study suggests that among patients on B cell depleting therapy, specifically with diagnoses of pediatric onset MS and related diseases, there is an increased risk of severe disease. There are a couple caveats to note though. One is that during the time period that we were collecting this data, the alpha and delta variants of COVID-19 were still circulating. This data was largely pre omicron, which we know to have a less severe phenotype. Moreover, this data represents a time period in which vaccinations had not been widely rolled out and there was limited testing availability. I think this study should raise everybody's awareness that there may be an increased risk of severe disease among this population of patients infected with COVID-19. There are a couple important disclaimers to keep in mind, namely, that the variant circulating now is different and less severe, and that vaccinations were not reflected in our study.

Although with the large population of patients to pull this data for the study, were there any limitations?

One of the biggest limitations in this study design was that this was research that was done in a standard of care visit. We asked for additional information from our colleagues and again, this was among a network of pediatric MS centers, but we could not control specifically for some of the comorbidities and we didn't collect data that I wish we had. For example, what was the immunoglobulin G or IgG serum concentration at the time that the person got sick? This is one lab value that could be really important to know and yet, because we were collecting this data during standard of care visits, it wasn't all unified. We didn't capture each of those data elements for all of our enrollees. If we were to do this again, we could roll it out with maybe more specific data elements. It would be helpful to know whether or not their B cells were actually depleted among this population who are on B cell depleting therapy, and exactly how long they'd been on it. We have some idea from our data, but [we want] to get more specific about how long they had been on that. Then, we’d like to know what the serum IgG level, which can tell us whether or not there was that additional complexity in terms of the immune response to COVID infection.

Is there anything you think clinicians who have patients with MS should know based on the findings?

Among our sickest patients­— the 5 patients who required ICU level care—we had body mass index data for 4 of them, and all four of them were obese. We know from other studies, including adult studies, this is a risk factor for severe COVID-19 infection. I just want to bring that additional detail to the minds of my colleagues as they are caring for these patients. If they are obese, and on B cell depleting therapy, there may be an additional risk.

We know that B cell depleting therapies are among the highest efficacy treatments for pediatric onset MS. Therefore, while this study offers us some information that we may need to pay particular attention to infection risk among these populations, we need to weigh that risk against the benefit of a well-controlled disease.

Transcript edited for clarity.

REFERENCES
1. Schreiner T, Wilson-Murphy M, Mendelt-Tillema J, et al. Characteristics of pediatric patients with multiple sclerosis and related disorders infected with SARS-CoV-2. Mult Scler. 2023;29(4-5):576-584. doi:10.1177/13524585231151948