COVID-19 outcomes in MS
Observational study of early experience from NYU Multiple Sclerosis Comprehensive Care Center

For this observational study, demographic and clinical features were collected on patients currently followed at MSCCC and its 4 affiliated sites in the greater New York area (2 in Long Island and 2 in Brooklyn) with a history of COVID-19 from March 16 through April 30, 2020. All patients who contacted the center with infectious symptoms or were seen during routine teleneurology visits were queried regarding COVID-19 exposure using a standardized instrument. Inclusion criteria were any patient with MS or related disorders who was diagnosed with COVID-19 by a health care provider (based on symptoms, course, radiographic findings consistent with CDC COVID-19 criteria,³ and/or positive SARS-COV2 PCR when available). For hospitalized patients, in-patient records were reviewed. NYU School of Medicine Institutional Review Board approval was obtained for the study.

Descriptive statistics were used to summarize the demographic and clinical characteristics of patient. Continuous variables were described in terms of means and SDs, and categorical variables were summarized as counts and percentages. No imputation was made for missing data. Differences between hospitalized vs nonhospitalized patients were compared by the t test, χ² test, or Fisher exact test as indicated, with CIs set at 95%.

A total of 76 patients met the inclusion criteria, 72 (93%) with MS, and 4 (7%) with related disorders (neuromyelitis optica spectrum disorder, chronic relapsing inflammatory optic neuropathy, neurosarcoidosis, and myelin oligodendrocyte glycoprotein-immunoglobulin G–associated disorder). The average age of the full sample was 44.9 ± 15.2 years (range 13–71 years), and 61.8% were female. The disease duration was 15.2 ± 10.7 years (range 1–52 years). Racial breakdown was 50 (65.8%) white, 21 (27.6%) black, 3 (3.9%) Asian, 1 (1.3%) Pacific Islander, and 1 (1.3%) other. Hispanic ethnicity was reported by 15 (19.7%). Of the 72 patients with MS, 55 (76.4%) had a relapsing-remitting subtype and 17 (23.6%) primary or secondary progressive subtypes. Sixty-five patients (84%) were on DMT. One patient resided in a nursing facility. He had an uncomplicated course.

Common symptoms reported included fever (68.4%), cough (68.4%), fatigue (38.2%), shortness of breath (31.6%), and myalgias/arthralgias (26.3%). Other frequent symptoms included anosmia (22%), ageusia (19.7%), and headache (21.1%). A subset reported neurologic symptom recrudescence (21.1%) suggestive of relapse. In some cases, neurologic symptoms preceded viral symptoms by several days.

Of the 84% of patients on DMTs, 44.7% were treated with anti-CD20 therapies (rituximab n = 18; ocrelizumab n = 16), 13.5% on sphingosine-1-phosphate (S1P) modulators (fingolimod n = 8; siponimod n = 2), 7.9% (n = 6) on glatiramer acetate, 5.3% (n = 4) each on natalizumab and dimethyl fumarate, and 3.9% (n = 3) on beta-interferons. Table 1 summarizes outcomes by DMT class. There were no observed differences between DMT use among those who were and were not hospitalized or between those specifically treated with anti-CD20 therapies (43% vs 50%, OR = 0.76 [CI 0.26–2.18]).

As shown in table 2, of the full sample, 18 (23.7%) were hospitalized. The hospitalized vs nonhospitalized patients were more likely to be older (CI 1.22–17.11, p = 0.03), have progressive MS subtype (OR 4.11 [CI 1.21–13.97], p = 0.04), required ambulatory assistance or were nonambulatory (OR 4.27 [CI 1.38–13.27], p = 0.01), and have comorbid obesity (OR 6.25 [CI 1.90–20.50], p = 0.003). Coronary artery disease (CAD) was observed in n = 3 hospitalized patients and no cases in nonhospitalized patients. History of venous thromboembolism was recorded in n = 3 hospitalized and n = 1 nonhospitalized patient.

Eight patients (10.5%) had critical illness defined by ICU admission (n = 5) and/or death (n = 6) (table 3). Compared with the entire MS sample, the critically ill patients were older (mean of 57.7 ± 10.5 years, range 42–71 years), more likely to have a progressive subtype (50.0%), and or required assistance for ambulation/nonambulatory (62.5% requiring assistance or nonambulatory). Following the pattern observed in those who were hospitalized, the critically ill group had had high rates of comorbid obesity (62.5%), CAD (25%), and venous thromboembolism (37.5%). There were no reports of stroke. One patient had hypercoagulability resulting in multiple venous thromboembolisms and ultimately died.

Nine patients with pediatric-onset MS were identified as the center has a large pediatric MS sample (table 4). Ages ranged from 13 to 26 years; 8 were female, and all had relapsing-remitting MS. Noted comorbidities were obesity (n = 3), type I diabetes (n = 1), or both (n = 1). Two of the 9 were hospitalized requiring supplemental oxygen. None required invasive ventilation. Eight patients were either fully recovered or recovering at censoring date. One remains hospitalized.

Patients with MS and related disorders often seek guidance regarding the impact of the disease and medication on their risk of COVID-19. This observational study—although subject to sampling and ascertainment biases—provides some insights regarding COVID-19 disease course in actively treated patients with MS and related disorders.

The rate of hospitalization in our patients (24%) and mortality (7.9%) are in line with the data of another published MS patient survey⁴ and for the general population of patients with COVID-19.⁵ Similar risk factors were identified including older age, male sex, and high number of comorbidities such as obesity, diabetes, hypertension, and CAD.^6–8 MS-specific features associated with more severe COVID-19 included nonambulatory status and progressive disease course. Given the small sample size, we could not determine whether these patients were at higher risk, given their advanced age and other comorbidities, or whether worse disability in and of itself represents an additional risk factor.

We did not observe an association between DMT class and COVID-19 outcome in univariate comparisons; however, our sample size is small, and these preliminary findings should be interpreted with caution. There is a relatively high proportion of COVID-19–infected patients on anti-CD20 therapies (44.7%) compared with our MSCCC population in which 33.1% of patients take anti-CD20 therapies. This observation could be an artifact of sampling bias or might represent an increased susceptibility to COVID-19 infection as anti-CD-20 therapies increase the risk of non-COVID-19 infections in general.¹ It is worth noting that although we had a larger-than-expected portion of patients on anti-CD20 therapies, there is no evidence to suggest worse outcomes.

As a note of caution in the care of patients with MS, a subgroup of individuals reported worsening of preexisting neurologic symptoms before or at onset of COVID-19 symptoms. One such patient was treated with several days of high-dose steroids after which they presented with respiratory and circulatory failure and ultimately died (table 3). Infections are a well-known cause of pseudoexacerbations, and in areas with high prevalence of COVID-19, testing for SARS-COV2 should be considered in patients with acute worsening of preexisting symptoms before steroid treatment is initiated.

Our study has several limitations. This was a convenience sample and not randomly selected, nor was the entire practice systematically surveyed. Patients were identified during routine teleneurology visits, if they notified the office, or if hospitalized—likely leading to an overrepresentation of more symptomatic individuals. Patients on higher potency infusible DMTs were more likely to have frequent follow-up and may have been more readily captured. In contrast, patients in nursing homes, who would be expected to be most severely affected by COVID-19, visit specialized centers less frequently and could be underrepresented in our cohort. Although we used a systematic questionnaire to collect relevant data, we could not verify these data independently unless the patient was seen by an NYU Langone-affiliated physician or hospital. Another problem was lack of access to COVID-19 testing in our area. Less than half of our patients (48.7%) underwent SARS-COV2 PCR testing. As shown in table 5, subgroup analysis showed that this group was not different from the overall sample with respect to demographic or MS-related features.

Our early experience with COVID-19 at NYU Langone MSCCC could inform clinicians taking care of patients with MS during the pandemic. Our findings suggest that individuals with MS who experience COVID-19 have similar disease course, outcomes, and risk factors for complications as the general population. Rigorous, population-based studies are needed to confirm our preliminary findings and better define the risk of COVID-19 infection with respect to individual DMTs. Future studies should assess the role of baseline lymphocyte counts and immunoglobulin levels with respect to viral susceptibility and course as well as examine the frequency of serologies to COVID-19 according to DMT class. As we and others collect more data and contribute to larger MS registries, we expect more answers will be forthcoming to further guide patient management.