COVID Risk Factors in Multiple Sclerosis Identified

Erik Greb

February 03, 2022

A younger age, the presence of comorbidities, and female sex are all factors associated with an increased risk for COVID-19 in patients with multiple sclerosis (MS), new research suggests.

In a case-control study that included 2337 patients with MS, the odds ratio (OR) for risk for COVID-19 infection among patients with comorbidities was 1.69 vs those without comorbidities.

The researchers also examined the relationship between treatment and risk for infection.

Dr Maria Trojano

"Choice of treatment strategy in general, and particularly during the COVID-19 pandemic, should take into account the potential increased risk of infections associated with the cumulative effect of disease-modifying therapy [DMT] sequencing on the immune system," investigator Maria Trojano, MD, professor of neurology at the University of Bari, Italy, told Medscape Medical News.

The findings were published online January 19 in Neurology: Neuroimmunology & Neuroinflammation.

Registry Data

After the emergence of SARS-CoV-2 in early 2020, researchers began investigating the risk that the virus posed for patients on immunotherapy.

There were national and international efforts to collect data and identify risk factors associated with COVID-19 severity in patients with MS. However, risk factors for the infection in MS had not been evaluated.

Trojano and colleagues conducted a case-control study using longitudinal, prospective data from the Italian MS Register (IMSR). They aimed to identify factors associated with risk for COVID-19 and with COVID severity.

IMSR data include COVID-19 diagnosis, date and severity of infection, and date of resolution or death. COVID-19 severity was classified according to neurologists' judgment. By the end of December 2020, data about vaccination status was also collected in the IMSR.

Also included was data on allergies, autoimmune diseases, cardiovascular diseases, epilepsy, headache, tumors, psychiatric disorders, and thyroid dysfunctions.

Participants included 779 patients with MS and confirmed COVID-19 infection, as well as 1558 patients with MS but without COVID-19 who were linked to the former group by propensity score matching.

Individuals who received the COVID-19 vaccine and did not become infected were excluded from the analysis.

Increased Risk with Natalizumab

Median age was 42.4 years among the case group vs 46.9 years among the control group (P < .0001). In addition, prevalence of comorbidities was 8.22% vs 5.26%, respectively, (P = .0054) and 70% vs 64% were women (P = .0066).

In all three primary logistic regression models that the investigators calculated, comorbidities and female sex were significantly associated with a higher risk for COVID-19 infection. The OR for risk for COVID-19 was 1.69 (P = .004) among those with comorbidities vs those without — and was 1.25 (P = .02) for women vs men.

Age was associated with a lower risk for COVID-19, and each additional year of age was associated with a decrease in risk for infection that ranged from 10% to 11%.

Natalizumab (Tysabri) was linked to a significantly higher risk of developing COVID-19 vs other DMTs (OR, 2.38). In addition, patients who switched from moderate- to high-efficacy DMTs were at higher COVID-19 risk (OR, 1.57) than treatment-naive patients and those who had only received first-line DMTs.

Moreover, receiving treatment at the hospital was associated with a significantly higher risk for COVID-19 compared with at-home self-administration (OR, 1.65).

Older age (P = .0004) and having progressive MS (P = .0067) were the most significant risk factors for a severe course of COVID-19. However, treatment with interferon beta (P = .0476) and remaining untreated (P = .0356) were associated with a lower risk for infection.

Long-Term Impact on Immune Function

"The risk of contracting COVID-19 in patients with MS may be more linked to the cumulative effect of long-lasting sequences of different immunotherapies than to the type of the last administered treatment," said Trojano.

An escalation treatment strategy, which entails multiple exposures to different DMTs, may chronically modify the immune system and increase susceptibility to infection, she noted.

"Some DMTs, indeed, are associated with long-lasting effects on the immune system, which can combine with the effects of subsequent therapies," she said.

Trojano noted the apparent increased risk associated with in-hospital treatment also has potential implications for practice.

"Greater attention must be paid to the safety of indoor environments, such as hospital waiting rooms," she said

The expanded use of telemedicine could also help reduce risk for COVID-19, she added.

"Alternative routes of administration should be considered for some drugs currently requiring a higher frequency of hospital attendance," Trojano said.

"More Activity, More Exposure"

Commenting on the findings for Medscape Medical News, Anthony T. Reder, MD, professor of neurology at the University of Chicago, Chicago, Illinois, said the investigators are eminent researchers and praised the quality of the analysis.

The availability of a national database of patients with MS, which the United States lacks, is a particular strength of this study, said Reder, who was not involved with the research.

Dr Anthony Reder

However, he also noted some limitations, including the use of propensity score matching. Although it increases confidence in the findings, potential sources of bias are sometimes missed during that process, said Reder. The comorbidities examined in the analysis were also not described in detail, he added.

"All the risk factors here point to more activity and more exposure," said Reder. The finding that women were more likely to be infected with COVID-19 does not mean they are physically more susceptible, he added.

"This is not a controlled situation. These women who are out and around and pretty healthy despite their MS are getting more social exposure to COVID."

Reder noted one surprising finding was that only 0.6% of patients with COVID-19 had an MS attack during their infection.

"That's strange, because viral infections in general are associated with MS attacks," said Reder. "Either COVID is different, or being on these treatments is preventing that virus-induced activation of MS."

In addition, the risk for infection in the healthcare setting that the investigators mention is more theoretical than real, he noted.

To get into his infusion center, "you've got to be afebrile and have no recent COVID exposure," Reder said. "I don't think we've ever had anybody get COVID in our infusion center."

The study was conducted without external funding. Trojano reported no competing interests related to the study but noted she had received compensation from Biogen, Merck, Novartis, and other companies that manufacture drugs for MS. Reder has disclosed no relevant financial relationships.

Neurol Neuroimmunol Neuroinflamm. Published online January 19, 2022.
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