Smoking, Most DMTs Not Associated With Severe COVID-19 in Patients With MS

Although obesity, diabetes, and certain comorbidities were all detected as risk factors for severe COVID-19 among people with multiple sclerosis (MS), other long-suspected risk factors, such as smoking and use of most disease-modifying therapies (DMTs), were not.

Smoking and use of most disease-modifying therapies (DMTs) were not among the risk factors identified to have an association with severe COVID-19 in patients with multiple sclerosis (MS), according to a recent literature review.

The review, which was published in Revue Neurologique, highlighted several risk factors in patients with MS that are linked to severe COVID-19 outcomes, including obesity, diabetes, and pulmonary and cardiovascular comorbidities, all of which have been suspected to be risk factors since the onset of the pandemic. However, the revelation that smoking and use of several immunosuppressive therapies are not among those risk factors may help guide clinicians to better assess individualized risk profiles and better manage patients in clinical practice.

“Close observations of these [people with MS] and raising awareness among themselves and their relatives to take the protective measures seriously, may be of more importance than the general population or other [people with MS],” wrote the investigators.

Since the COVID-19 pandemic began, concerns were raised among the general MS population and their physicians regarding disabilities, immunosuppressive therapies, and higher susceptibility to infections and serious outcomes. Results from studies investigating the possible relationships between COVID-19 risk factors and MS have been divergent as most have been primary observational investigations.

The investigators conducted a comprehensive search of 4 literature databases in May 2021 to find observational studies assessing COVID-19 severity among adults (over 18 years). The studies also had to include laboratory- or radiology-based diagnoses or high clinical suspicion of COVID-19, categorize different severity levels of COVID-19, estimate the outcome of possible predefined risk factors, and be published in English. During the analysis, COVID-19 severity was classified as either mild or severe, with the later indicating that a patient was hospitalized for COVID-19–related complications, regardless of admission to an intensive care unit or final disease outcomes.

Overall, 13 eligible studies with data on a total of 4728 patients were included in the final analysis. The studies either comprised data from multiple countries or hailed from Italy, France, Turkey, Spain, the Netherlands, Iran, Spain, or the United States. There were 22 risk factors assessed across the studies.

The final results of the meta-analysis demonstrated statistically significantly associations between severe COVID-19 and male sex (P = .039), glatiramer use (P = .012), obesity (P = .002), diabetes (P < .001), pulmonary comorbidities (P = .007), cardiovascular comorbidities (P < .001), hypertension (P = .001), progressive MS (P < .001), an Estimated Disability Status Scale (EDSS) score between 3 and 6 (P = .001), an EDSS score over 6 (P = .001), longer disease duration (P < .001), corticosteroid use in past 2 months (P < .001), and use of a CD20 inhibitor (P = .008).

However, current or past smoking (P = .845) and use of glatiramer (P = .358), teriflunomide (P = .125), fumarate (P = .116), fingolimod (P = .222), natalizumab (P = .342), alemtuzumab (P = .698), or cladribine (P = .148) had no association with severe COVID-19. Additionally, interferon use was found to significantly reduce the odds of severe COVID-19 (P = .001).

“Most DMTs did not show to be associated with a severe COVID-19, and therefore, they can be continued with caution throughout the pandemic; with anti-CD20 drugs, however, the issue is slightly different….but whether or not anti-CD20 treatments should be halted or replaced by other therapies is controversial, and more practical approaches may be more appreciated,” the investigators wrote.

The investigators noted that among the studied factors, patients who had the progressive phenotype of MS had an almost 4 times higher risk of severe COVID-19, calling the multiplied risk “alarming.” Furthermore, they recommended that vaccination against COVID-19 should be prioritized for patients with MS and that patients should be advised to receive booster doses and to continue following protective measures even after vaccination.

The study had some limitations, including the 2-level outcome measurement and the small number of team members that conducted the database search, suggesting that some relevant information may have been omitted.

“There is still a need for more evidence to estimate the effects of mentioned risk factors more precisely on the course of COVID-19. Future studies can also focus on the mechanistic processes which render [people with MS] with risk factors more susceptible to COVID-19,” the investigators noted.


Etemadifar M, Nouri H, Maracy MR, et al. Risk factors of severe COVID-19 in people with multiple sclerosis: a systematic review and meta-analysis. Rev Neurol. Published online November 4, 2021. doi:10.1016/j.neurol.2021.10.003