key: cord-1034601-y69w57wq
authors: Chaudhry, F.; Bulka, H.; Rathnam, A. S.; Said, O. M.; Lin, J.; Lorigan, H.; Bernitsas, E.; Rube, J.; Korzeniewski, S. J.; Memon, A. B.; Levy, P. D.; Javed, A.; Lisak, R.; Cerghet, M.
title: COVID-19 in Multiple Sclerosis Patients and Risk Factors for Severe Infection
date: 2020-05-29
journal: nan
DOI: 10.1101/2020.05.27.20114827
sha: b4469e2e744671d3fef2791ddebc3acef1b07a81
doc_id: 1034601
cord_uid: y69w57wq

Importance: Multiple sclerosis patients have been considered a higher-risk population for COVID-19 due to the high prevalence of disability and disease-modifying therapy use; however, no study has identified clinical characteristics of multiple sclerosis associated with worse COVID-19 outcomes. Objective: To evaluate the clinical characteristics of multiple sclerosis, including staging, degree of disability, and disease-modifying therapy use that are associated with worse outcomes from COVID-19. Design: Prospective cohort study looking at the outcomes of multiple sclerosis patients with COVID-19 between March 1st and May 18th, 2020. Setting: This is a multicenter study of three distinct hospital systems within the U.S. Participants: The study included 40 consecutive patients with nasopharyngeal/oropharyngeal PCR-confirmed COVID-19 infection. Exposures: Multiple sclerosis staging, severe disability (based on baseline-extended disability status scale equal to or greater than 6.0) and disease-modifying therapy. Main Outcomes and Measure: Severity of COVID-19 infection was based on hospital course, where a mild course was defined as the patient not requiring hospital admission, moderate severity was defined as the patient requiring hospital admission to the general floor only, and most severe was defined as requiring intensive care unit admission and/or death. Results: For the 40 patients, the median age was 52(45.5-61) years, 16/40(40%) were male, and 21/40(52.5%) were African American. 19/40(47.5%) had mild courses, 15/40(37.5%) had moderate courses, and 6/40(15%) had severe courses. Patients with moderate and severe courses were significantly older than those with a mild course (57[50-63] years old and 66[58.8-69.5] years old vs 48[40-51.5] years old, P=0.0121, P=0.0373). There was differing prevalence of progressive multiple sclerosis staging in those with more severe courses (severe:2/6[33.3%]primary-progressing and 0/6[0%]secondary-progressing, moderate:1/14[7.14%] and 5/14[35.7%] vs mild:0/19[0%] and 1/19[5.26%], P=0.0075, 1 unknown). Significant disability was found in 1/19(5.26%) mild course-patients, but was in 9/15(60%, P=0.00435) of moderate course-patients and 2/6(33.3%, P=0.200) of severe course-patients. Disease-modifying therapy prevalence did not differ among courses (mild:17/19[89.5%], moderate:12/15[80%] and severe:3/6[50%], P=0.123). Conclusions and Relevance: Multiple sclerosis patients with more severe COVID-19 courses tended to be older, were more likely to suffer from progressive staging, and had a higher degree of disability. However, disease-modifying therapy use was not different among courses.

moderate courses, and 6/40(15%) had severe courses. Patients with moderate and severe courses were significantly older than those with a mild course (57 [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] [62] [63] years old and 66 [58.8-69.5] years old vs 48 [40-51.5 ] years old, P=0.0121, P=0.0373). There was differing prevalence of progressive multiple sclerosis staging in those with more severe courses 

Multiple sclerosis patients with more severe COVID-19 courses tended to be older, were more likely to suffer from progressive staging, and had a higher degree of disability. However, disease-modifying therapy use was not different among courses.

Patients with multiple sclerosis (MS) are four times more likely to succumb to serious infection when compared to the general population, making them potentially at higher-risk from the ongoing novel coronavirus disease . 1 This may be because a significant number of MS patients have a high level of disability and are on immunosuppressive disease-modifying therapies (DMTs). Most information regarding the association of MS characteristics and DMTusage with COVID-19 comes from case-reports and case-series surveys. 2,3 In this prospective cohort study we looked at the MS disease characteristics with differing COVID-19 severity. (Table 1b) Overall, initial presenting symptoms were similar among each course of COVID-19. (Table 1c) All moderate and severe courses, as expected, had chest X-ray obtained compared to only All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

MS is a heterogeneous disease as PPMS and SPMS are associated with a later age of onset when compared to RRMS, thus patients tend to be older with more disablities. 9,10 Older age, certain comorbidities and living in nursing homes are significant risk factors for Indeed, MS patients with moderate-severe courses were more likely to have progressive disease, comorbidities (smoking, hypertension, and diabetes), and EDSS scores > 6.0. These patients also tended to be older and frequently resided in nursing homes.

It is known that certain DMTs have higher infectious risk compared to others; therefore, it has been a concern that cell depleting DMTs would be associated with higher COVID-19 risk. 12 However, in our cohort, there doesn't appear to be bias regarding certain DMTs in moderatesevere courses. In fact, it appears that more patients with moderate and severe courses were not on any DMT compared to that seen in those with mild courses. DMTs have been hypothesized to attenuate the cytokine-storm response in COVID-19, though this is still purely speculative. 12 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 29, 2020. . https://doi.org/10. 1101 /2020 Overall, usage of DMTs do not necessarily appear to be associated with more severe COVID-19courses. These findings correspond to those in ongoing North American COVID-19 MS survey database (covidms.org) and Italian cohort surveyed by Sormani el al. where patients who died tended to be older, have PPMS or SPMS, and have significant disability and comorbidities, but were less likely to be on DMT. 3, 13 As of 5/25/2020, the Detroit Health Department has reported a 12.3% citywide COVID-19 mortality rate among laboratory confirmed cases. 14 Although, we had a small sample size, our MS cohort reported a similar mortality rate and was like that reported by Sormani et al. in confirmed-COVID-19 positive MS patients (5/57[8.78%]). 3 Therefore, we can assume our mortality rate could be consistent with a larger sample size and similar to that of the general population.

A significant limitation to our study is the relatively small sample size collected; therefore riskstratification adjusting for confounders was not possible. Larger studies are therefore required in order to improve for confounding variables. Also, there was a significant discrepancy in samplesize for each course, as there were only 6 patients with severe disease course. Therefore, significant differences may not have been detected in post hoc comparisons with this course.

Regardless, we showed that certain MS-characteristics were more frequent in more COVID-19 severe courses. All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 29, 2020. . https://doi.org/10. 1101 /2020 Data Availability: Due to the sensitivity of protected health information, de-identified data will only be available upon request to corresponding author.

All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 29, 2020 . . https://doi.org/10.1101 /2020 

Healthcare Worker 6/40 (15%)

Diabetes 6/40(15%)

/19 (0%)

Elevated Ferritin

/mL 12/16 (75%), 24 labs not obtained

3/4 (75%)

Elevated CRP;median(IQR) mg/dL 16/16 (100%) 24 labs not obtained