By Jai S. Perumal, MD
Assistant Professor of Neurology, Weill Cornell Medical College; Assistant Attending Neurologist, New York-Presbyterian Hospital
Dr. Perumal reports she is a consultant for Biogen and Genzyme.
SYNOPSIS: In a multicenter, retrospective analysis of patients in a multiple sclerosis (MS) registry, the authors described the clinical characteristics and risks associated with severity of complications from COVID-19 infection in patients with MS. The risks were similar to those in the general population, including age, obesity, male sex, and cardiopulmonary comorbidities, but also the level of baseline MS disability. Being on a disease-modifying therapy did not seem to increase the risk of severe COVID-19 disease, but multiple immunosuppressive medications were associated with a higher risk of serious complications.
SOURCE: Louapre C, Collongues N, Stankoff B, et al, for the Covisep investigators. Clinical characteristics and outcomes in patients with coronavirus disease 2019 and multiple sclerosis. JAMA Neurol 2020;77:1-10.
This study reviewed data from 347 multiple sclerosis (MS) patients in a nationwide registry in France between March 1 and May 21, 2020. All patients met the diagnostic criteria for MS and were confirmed or highly suspected of having had COVID-19 infection based on at least one of the following: SARS-CoV-2 polymerase chain reaction on nasal swab, typical chest computed tomography findings, acute onset anosmia or ageusia without another explanation, or other typical COVID-19 symptoms, including the triad of cough, fever, and asthenia in an epidemic zone.
The main objective of the study was to assess the association between COVID-19 disease severity based on a seven-point ordinal scale ranging from 1 (not hospitalized and no limitations in activities) to 7 (death). In addition, patient demographics, disability as measured by the Expanded Disability Status Scale (EDSS), comorbidities, and MS disease-modifying therapy (DMT) were collected. The mean age (standard deviation) of the patients was 44.6 years, the mean disease duration was 13.5 years, and the mean EDSS was 2 (range 0 to 9.5). Of the 347 patients, 249 were women and 284 (81.8%) patients were taking DMT. Demographic data were compared between patients with COVID-19 disease severity scales 1 and 2, and patients with COVID-19 disease severity scales 3 or more (indicating hospitalization or death). The DMTs for MS were grouped according to systemic infection risk: 1) no risk (glatiramer acetate and interferon); 2) low risk (teriflunomide, dimethyl fumarate, and natalizumab); and 3) intermediate or high risk (fingolimod, anti-CD20 therapies, cladribine, and alemtuzumab).
Seventy-three (21%) patients had a COVID-19 disease severity of 3 or more. Patients in this more severe disease category were more frequently male, were older (55 years of age vs. 41.9 years of age; P < 0.001), had more disability (EDSS 6 vs. 2; P < 0.001), and more often had a progressive disease course (36/73 vs. 29/274; P < 0.001). Obesity and the presence of cardiopulmonary comorbidities also were associated with an increased rate of hospitalization. In this study, there was a higher proportion of severe disease among patients who were not taking a DMT compared to those who were taking a DMT (26/63 [46%] vs. 44/284 [15.5%]; P < 0.001). The authors speculated that differences in baseline demographics of those taking treatment vs. those not taking treatment might be a reason for this finding, but they also noted this has to be explored further. However, among patients on DMT, there was higher rate of severity of COVID-19 disease in patients taking one of the intermediate- to high-risk medications when compared to one of the low- or no-risk medications (24/1,010 [23.8%] in high-risk vs. 17/130 [13.1%] in the low-risk and 3/53 [5.7 %] in the no-risk group; P = 0.007). Using multivariate analysis, they found that male sex, obesity, cardiopulmonary comorbidity, and higher EDSS were independent variables associated with severe COVID-19 disease. Twelve (3.5%) patients died from COVID-19, with most having significant baseline MS disability and progressive disease. This percentage is higher than what is reported in the general population. Four patients required mechanical ventilation and three were on anti-CD20 therapies. One had progressive disease and the other two had obesity as a comorbidity. Although their comorbidities would increase their risk of severe disease, immune suppression with these medications could have played a role as well. Since their data did not seem to indicate generally that patients taking a DMT were at significantly higher risk for severe COVID-19 disease, the authors concluded that patients with high inflammatory activity and risk of disability should be started or continued on DMT, but one should exercise caution when using DMTs in patients with significant baseline disability and older age.
Given the ongoing COVID-19 pandemic, and the relative dearth of detailed data, the risks associated with immunosuppressive treatment for conditions like MS and the severity of complications from it remain major concerns for patients and the clinicians treating them.
In this study, the authors found that the risks associated with more severe COVID-19 disease were similar to those in the general population, including, among others, age and obesity. Progressive disease and more severe baseline disability also were associated with a higher risk. The lack of association between taking a DMT and severity of COVID-19 disease is likely the result of the baseline demographics of patients taking a DMT, who tend to be younger and have less advanced disease. However, among the DMTs, the more immunosuppressive treatments were associated with more severe COVID-19 disease. In addition, even though the numbers were small, among four patients who required mechanical ventilation, three were on anti-CD20 targeted therapy, which is a significant immune suppressive treatment for MS. It would be prudent to be cautious before starting or continuing this or similar immune suppressive treatment for patients and to assess the need on an individual basis. This study also found that older, progressive, and more disabled patients were at higher risk for severe COVID-19 infections. We also know from published data regarding the efficacy of DMTs that this patient population is least likely to benefit from a DMT. Therefore, even more so during this pandemic, one should be wary of immune suppression for MS in this group.
Overall, the data from this study provide some reassurance in general about MS treatment and COVID-19 disease severity, but it is vital that one assess the risks vs. benefits individually and carefully before starting and/or continuing a DMT. For patients on immune suppressive treatment, we must educate them about COVID-19 infections and emphasize that they follow all measures diligently to decrease the risk of potential exposure to COVID-19.