Objective: To investigate the frequency of coronavirus disease (COVID-19) in patients with multiple sclerosis (pwMSs) living in a high socioeconomic vulnerability area in Chile.

Methods: In this prospective cohort study, we compared the frequency of COVID-19 in 52 Chilean pwMSs on disease-modifying treatments (DMTs), living in urban municipalities with low-income/high-poverty levels, with that previously reported in pwMSs living in municipalities with high-income/low-poverty rates in Santiago, Chile. Demographic and clinical features of the pwMSs were obtained from their last consultation between March 3, 2020, and August 29, 2020.

Results: In the low-income pwMSs, the mean patient age was 34 years, 69% were women, mean disease duration was 3 years, and mean Expanded Disability Status Scale score was 1.6. Of these, 61.5% pwMSs (32/52) underwent quarantine during the study period. COVID-19 diagnosis was confirmed by reverse transcriptase polymerase chain reaction in five patients (10%): two were on glatiramer acetate, one was on fingolimod, and two were on alemtuzumab. All pwMSs with COVID-19 recovered fully. The previously reported frequency of confirmed COVID-19 in middle‒upper income pwMSs living in Santiago was 1%. The frequency of COVID-19 among pwMSs in the low- and middle‒high income inhabitants of Santiago differed significantly (z = -4.3235, p < 0.00001; one-tailed Fisher exact test, p < 0.01).

Conclusion: The frequency of COVID-19 in the low-income/high-poverty cohort in Santiago, Chile, was markedly high. Accordingly, high socioeconomic vulnerability should be considered as an important risk factor for COVID-19 in pwMSs.

This was a prospective cohort study that included 52 adults with MS defined according to the revised McDonald criteria. These pwMSs were followed-up at the University of Chile Hospital and San Juan de Dios Hospital, Santiago, Chile. Inclusion criteria were age 18 years or older, a minimum of 5 months of follow-up per patient during the COVID-19 pandemic, with an entry assessment in March (since March 3rd, 2020) and at least a second assessment at month 5 (until August 29th, 2020). Direct interviews between the patients and the treating neurologists were part of the inclusion criteria. These interviews were conducted during the hospital appointments, hospitalization for DMT infusions or COVID-19 treatments, or over the telephone. Online questionnaires were not used. Patients with clinically isolated syndrome were excluded. This study was part of routine clinical practice, and therefore, the treating neurologists were free to make any therapeutic change. Because of the observational nature of the study, no further inclusion criteria were defined. We note that these two hospitals provide medical assistance to patients living in municipalities with higher poverty rates than the average in Santiago of Chile, both in terms of income and of multidimensional poverty. Multidimensional poverty is defined as a composite index consisting of scores assessed in four dimensions: Education, Health, Work and Social Security, and Housing. It is an official supplementary measure for the income-based national poverty index in Chile.

We further assessed the association of MS with COVID-19 by comparing a matched sample with our original cohort. To achieve this, we contacted our original participants, re-interviewed them in order to obtain new information, and then found a person similar in terms of sex and age living in the same neighborhood. The process of contacting the matching cases was carried out directly by the research team, and the non-MS participants were interviewed via phone. This complementary survey strictly referred to the study period (March 3, 2020 to August 29, 2020). We obtained a matched sample of 52 pairs of participants, each pair sharing the same sex and age group and living in the same neighborhood. The average estimated distance between the households of the pwMSs and their controls was 106 meters (SD: 103.9). We used the body mass index (BMI) to define overweight (BMI 25–29.9) and obesity (BMI >30). Physical activity was described as sedentary behavior, light intensity physical activity, and moderate physical activity.16,17 We used a direct self-report measure of income based on the National Socioeconomic Characterization Survey. We included the number of residents, bedrooms, and bathrooms in the households of both PwMSs and their matched controls.

All patients were surveyed by questionnaire on demographic and clinical features, on whether they had followed the World Health Organization’s guidelines on preventive measures for reducing COVID-19 transmission, including social distancing and frequent hand-washing with soap and water or alcohol-based hand sanitizer. According to the ISN guidelines, the participants were also asked whether they followed governmental guidelines on facemasks and quarantine. Additional questions centered on whether they had been in contact with a person with SARS-CoV-2 infection or had experienced COVID-19-related symptoms. Cases with suggestive symptoms were assessed by SARS-CoV-2 polymerase chain reaction (PCR) testing on a nasopharyngeal swab. Absolute lymphocyte counts (ALC) obtained during the COVID-19 pandemic were reported for patients with natalizumab, ocrelizumab, and alemtuzumab. Lymphopenia was defined as grade 1: ALC 800‒999/ul; grade 2: ALC 500–799/μl; grade 3: ALC 200‒499/μl and grade 4: ALC < 200/μl.

Statistical analysis

Analyses of the clinical data and clinical-imaging correlations were performed using the Statistical Package for Social Sciences (IBM Corp., Armonk, NY, USA, version 22). The results are presented as the mean ± standard deviation (SD).  In all cases, a two-sided p value of <0.05 was considered significant. Monthly income, BMI, and measures related to household members were compared using a two-tailed t-test.  Fisher´s exact test was used to compare proportions between pwMSs and their neighbors. We compared differences in the proportion of pwMSs with COVID-19 in this cohort with that in other cohorts in Chile recently reported in the literature. Study 1 was based on an online sample drafted from pwMSs at a single, private MS-treatment center and residing in more socioeconomically advantaged areas in Santiago, Chile, and reported a frequency of COVID-19 among pwMSs of 1.1%.19 Another national multicentric investigation, involving 327 pwMSs (79%) with private medical insurance and 77 pwMSs (19%) with public medical insurance, by the same team as Study 1, reported a frequency of COVID-19 among pwMS of 3.5%, based on online surveys.20 Study 1 and Study 2 started at the beginning of the pandemic in Chile, but they closed earlier that ours (Study 1 closed in May 7th and Study 2 in June 22sd).  To assess if the differences in COVID-19 proportions between this study and previous ones were significant, we performed both a z-test and Fisher’s exact test for two reasons. 1) The z-test is a proportions test used to determine whether two population proportions are different when the variances are known and the sample size is large; in this case, because of the total sample size, we used it to identify initial differences. 2) Fisher's exact test is a chi-square-based test, which, because of its exact calculation, is appropriate for small sample sizes; we used Fisher’s exact as a way to confirm the initial differences found by z-tests.