North American, European Registry Data Show Impact of COVID-19 in Multiple Sclerosis

Anne H. Cross, MD

At the 2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC), October 25-28, Anne H. Cross, MD, professor of neurology; and the Manny and Rosalyn Rosenthal – Dr. John Trotter MS Chair in Neuroimmunology, Washington University in St. Louis, presented registry data on the effect of COVID-19 on patients with multiple sclerosis (MS), as well as the impact of individual disease-modifying therapies (DMTs) on the severity of COVID-19 outcomes. 

Registry data from a multitude of sources, including the COViMS registry in North America (n = 3452) and European registries (n = 1787), suggest that patients with MS who are older, male, more disabled, and those with comorbidities are likely to develop worse cases of COVID-19 when and if they do contract the infection.

In North America, with every 10 years of age, risk of death increased by 87.5% (P <.0001), while male gender increased the risk of death by 2.2 times (P <.0077). Black patients in North America also had risk increased by 2.5 times for hospitalization, admission to the intensive care unit, and use of a ventilator, but not an increased risk of death, when compared to White and Hispanic patients. 

Data further suggested that worse COVID-19 outcomes were associated with B-cell depleting agents, as well as treatment with methylprednisolone in the prior month to contracting the virus. According to electronic medical record data, those taking glatiramer acetate and ß interferons had a reduced incidence of the virus. Those taking ß interferons also had better COVID-19 outcomes in the event they did contract the virus. 

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Combined registry data suggest that while worsening of pre-existing symptoms are commonly reported, they are not universal, and there is no evidence that COVID-19 causes true exacerbations or the onset of MS itself. Cross commented on this pseudo-exacerbation in her presentation, stating, “My conclusion after looking through the literature is that we need more studies—that would be the first one, and we need better, and probably prospective studies, but it seems like worsening of preexisting symptoms is very commonly reported—what we would call a pseudo-exacerbation, and I didn’t find any evidence that I would conclude that COVID-19 actually causes true exacerbations of MS or MS onset…but we need better studies.”

COVID-19 Vaccination and Disease Severity

A question about COVID-19 vaccination was added to the COViMS registry as of April 27, 2021. According to data through October 5, 2021, 240 patients who had COVID-19 in 2021 addressed the question, 100 (42%) of whom had not been vaccinated, 99 (41%) who had been vaccinated, and 41 (17%) who were unknown. 

While addressing the potential for bias, Cross noted that patients who were taking ocrelizumab (Ocrevus; Genentech) had no significant reduction in hospitalization after vaccination. As of October 15, 2021, 8 deaths from COVID-19 had been reported in the COViMS registry. Most of the patients had received the Pfizer/BioNTech COVID-19 mRNA vaccine, BNT162b2, 5 out of 8 patients were on a B-cell depleting agent, and all deaths were from the United States.

Cross also discussed recommendations for treating high-risk patients with MS who do contract COVID-19, highlighting the use of anti-SARS-CoV-2 monoclonal antibodies. She called attention to the use of casirivimab and imdevimab (REGEN-COV; Regeneron), which decrease patients’ risk of being hospitalized by over 80% when combined.

Data From International Registries 

Cross also presented data from an Italian MS registry of suspected or confirmed COVID-19 infection (n = 844), prior to vaccination, which reported an overall mortality rate of 1.5% (13 total deaths). Of these patients, 11 had progressive MS and only 5 were being treated with DMTs.

This registry found that anti-CD20s, including rituximab (Rituxan; Genentech/Biogen) and ocrelizumab, were associated with a more severe course, and recent use of methylprednisolone was associated with worse outcomes, both conclusions that were also drawn from the North American registry. More recent pooled data from Italy and France of confirmed COVID-19 cases found that those on anti-CD20s had higher rates of hospitalization, ventilation, stay in the ICU, and death, when compared to those on beta-interferons.

Development and Limitations of COVID-19 Registries in MS

In North America, the COViMS registry was developed to address the gap in information on COVID-19 infections in patients with MS. Health care providers enter patient data for those with confirmed or suspected COVID-19 infection after a minimum of 7 days. Data collection began on April 1, 2020, and data presented at CMSC 2021 spanned through October 5, 2021. As of October 5, the registry had 88 reported deaths.

Certain limitations of registry data were highlighted by Cross, including the possibility of ascertainment bias, as patients information was voluntarily submitted, as well as differences in behavior across populations over time and geographical region. There have also been alterations in treatment of COVID-19 since the onset of the pandemic and new virus variants have emerged. Data may have been skewed by patients taking DMTs receiving the vaccine at difference rates, Cross said.

With new COVID-19 virus strains and additional waves of disease, Cross further stressed the importance to log data in the registry, as well as monitor outcomes and DMT interactions for this patient population.

For more coverage of CMSC 2021, click here.

REFERENCE

Cross AH. The effect of COVID-19 on MS and the effect of DMTs on COVID-19. Presented at CMSC 2021; October 25-28. Part of SYM01-Viral infections in MS: What have we learned from COVID-19.