key: cord-0947165-aoibe8fo authors: Zanghì, Aurora; D'Amico, Emanuele; Luca, Maria; Ciaorella, Marco; Basile, Lucia; Patti, Francesco title: Mental health status of Relapsing-Remitting Multiple Sclerosis Italian patients returning to work soon after the easing of lockdown during COVID-19 pandemic: a monocentric experience date: 2020-10-03 journal: Mult Scler Relat Disord DOI: 10.1016/j.msard.2020.102561 sha: b12ed7f88aef9930cccc66aa4b9f3836ce9488ab doc_id: 947165 cord_uid: aoibe8fo BACKGROUND: The prolonged lockdown related to COVID-19 pandemic determined disruption of lifestyle and social isolation. METHODS: To assess the mental health status of Relapsing-Remitting Multiple Sclerosis (RRMS) patients regularly followed at the MS centre of Catania (Italy) and returning to work after the easing of lockdown during COVID-19 pandemic. Then, to identify any variables associated to psychological distress.RRMS patients returning to work during the COVID-19 pandemic were invited to answer a telephonic interview consisting of the administration of the Short-Screening-Scale for DSM IV (SSS-DSM-IV), the Depression, Anxiety, Stress Scale- 21 (DASS-21) and the Insomnia Severity Index (ISI). Other information was extracted from electronic medical records. RESULTS: Valid and complete interviews were obtained from 432 patients (response rate 64.3%). Out of them, 277 (64.1%) were female, mean age 40.4 (SD 12.4) years. One-hundred thirty-seven (31.7%) RRMS patients received a score ≥4 at the SSS-DSM-IV, indicating clinically significant PTSD-like symptoms. About DASS-21, moderate-to-severe anxiety was reported by 210 RRMS patients (48.6%), moderate-to-severe depression, and moderate-to-severe stress were respectively reported by 95 (22%) and 220 (50.9%) RRMS patients. Insomnia was reported by 128 patients (29.6%). Factors associated with major severity of symptoms were: marital status, previous diagnosis of mood disorders, switching/starting Disease-Modifying Therapies in the last 12 months, and a higher level of disability measured with Expanded Disability Status Scale (for all, p<0.05). CONCLUSIONS: Our findings highlight the need to provide psychological support to MS patients facing the delicate phase of returning to work and to normal activities. In December 2019, the Coronavirus Disease 2019 (COVID-19) pandemic infection firstly occurred in China and, after three months, it became ubiquitous with hundreds of thousands of confirmed cases worldwide. Italy was the first European country to deal with the effects of the COVID-19 pandemic. Prolonged lockdown and business closure determined disruption of lifestyle, social isolation, and loss on personal incomes. For people with multiple sclerosis (MS), the situation carries additional reasons for concern, due to the use of immunosuppressive therapies. (1) . Notably, the neuropsychiatric correlates of MS relate to disease exacerbations and decreased treatment adherence (2) . The neuropsychiatric effects of the viral pandemic on the general population have been previously demonstrated in China. In a cross-sectional study conducted during COVID-19 pandemic, 53.8% of the 1210 respondents reported a moderate-to-severe psychological impact of the outbreak (3). Another research showed anxiety and stress disorder rates to be 23% and 27% respectively among the medical staff of a hospital in China(4). In Italy since May 4 th , 2020 the government approved the gradual return to work and to normal activities. Zanghì et al. The primary aim of this study was to assess the mental health status of a sample of Relapsing-Remitting Multiple Sclerosis (RRMS) patients regularly followed at the MS centre of Catania (Italy) and returning to work after the easing of lockdown during COVID-19 pandemic. The secondary aim was to identify any variables associated to psychological distress that could inform clinical practice. After the government approval of gradual return to work, patients with RRMS regularly followed at the tertiary MS centre of Catania (Italy) were invited to participate in the study, conducted from 4 May to 22 May 2020. The short recruitment period allowed to measure the psychological distress experienced by RRMS patients in the immediacy of their return to work during COVID-19 pandemic. Specific questionnaires were administered via telephonic interviews, since face-to-face encounters were reserved to emergencies only, in accordance with the local regulations seeking to limit the spread of COVID-19. The study protocol was approved by the local ethics committee (Comitato Etico Catania 1, n.85/2020/PO) Patients provided written informed consent. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki and with the appropriate national regulations. Zanghì et al. Patients with RRMS were selected through the consultation of the electronic medical records registered in the iMed© (Merck-Serono, Geneva) software (5), routinely used in our MS centre. Key eligibility criteria were: 1) having a diagnosis of RRMS according to the revised 2010 McDonald criteria (6) and 2) being employed in a job before the outbreak of the pandemic. The exclusion criteria consisted in the inability to complete the telephonic interview and the presence of a previously diagnosed cognitive impairment. In clinical practice, patients are classified as having cognitive impairment when they fail at least three neuropsychological tests belonging to the Brief Repeatable Battery (BRB) of Neuropsychological Tests (7) and Stroop test (8), in the light of previous studies using the same neuropsychological battery and reporting that less than 5% of healthy controls failed more than three tests (9-11). The following sociodemographic data were collected: age, gender, marital status, type of occupation, weekly working hours. The considered clinical data were: disease duration, line of The presence of anxious-depressive symptoms and complaints of distress was assessed using the Depression, Anxiety, and Stress Scale (DASS-21), whereby the calculation of scores was based on previous studies (14) . DASS-21 has been demonstrated to be a valid measure of mental health during COVID-19 pandemic (15) (16) (17) . The sleep quality of respondents was measured through the Insomnia Severity Index (ISI) (18) . The total ISI score was divided into: no clinically significant insomnia (0-7), subthreshold insomnia (8-14), moderately severe clinical insomnia (15) (16) (17) (18) (19) (20) (21) and severe clinical insomnia (22-28). The categorical variables were reported as number and percentage (%), while the continuous ones were expressed in terms of mean ± standard deviation (SD) or median with interquartile range (IQR). The proportions were compared through chi-square test. The level of significance was set at 0.05. Multiple linear regression with a backward selection method was used to examine the association between the outcome variables (SSS-DSM-IV, DASS-21 and ISI scores) and both demographic and clinical variables. All the analyses were conducted using IBM SPSS Statistics 21. Anonymised data will be shared upon request from any qualified investigator for the sole purpose of replicating procedures and results presented in the report, provided that data transfer is in agreement with EU legislation on the general data protection regulation. From a total cohort of 1350 patients with RRMS, 672 fulfilled the inclusion criteria. Valid and complete interviews were obtained from 432 patients, with a response rate of 64.3%. The mean age was 40.4 (SD 12.4) years, and the majority of respondents were female (n=277; 64.1%). A total of 70.3% patients were married, 17.4% were single, and 12.3% were divorced or widowed. Concerning the occupational characteristics, 77.5% of the respondents were employees or selfemployed, while 22.5% were executives and with management roles. The mean prepandemic working hours was 41.3 (SD 4.2) hours/per week (in Italy the average working hours per week is 40 hours)All the enrolled patients had returned to work for a maximum of 10 days after the easing of lockdown and mean working hours was reduced to a mean of 36.2 (SD 3.2) hours per week. Zanghì et al. The mean disease duration of the enrolled patients was 64 (SD: 38.1) months. The median EDSS at last visit was 1. The mean SSS-DSM IV score was 3.5 (SD: 1.0) ( Demographics and clinical predictors of the score at each questionnaire are showed in Table 2 . For demographics, divorced or widowed patients had a significantly higher score at DASS-21 stress (p = 0.00) when compared to single or married respondents. Patients with psychiatric comorbidities showed higher scores at SSS DSM IV (p = 0.00), DASS-21 depression (p =0.00), DASS-21 stress (p = 0.00) and ISI (p= 0.001). A higher EDSS was predictive of higher scores at SSS DSM IV (p = 0.00). Patients who had started their first DMT or had switched DMT within the last 12 months had significantly higher scores at the SSS DSM IV (p = 0.00), DASS-21 anxiety (p =0.00), DASS-21 depression (p = 0.00), DASS-21 stress (p = 0.00) and ISI (p= 0.00). In our cohort of RRMS patients the return to work was associated with the presence of psychiatric concerns that were higher in patients who have started /switched DMTs in the last 12 months or in those with higher levels of disability. Notably, symptoms were exacerbating in RRMS patients with previous diagnosis of psychiatric comorbidity. Patients with MS are known to undertake maladaptive coping strategies (19) which make them even more susceptible to the detrimental neuropsychiatric effects of the outbreak. As a matter of fact, regardless to the pandemic, anxiety and depression have been reported in up to 57% (20) and 40% (21) of MS patients respectively and these rates are highly above those recorded in general population. Zanghì et al. Additionally, RRMS therapy has drastically changed in the last years, with many DMTs of increased efficacy but with a broad spectrum of action on the immune system. RRMS patients have a theoretically increased risk of being infected and they are aware of it (22). The return to normal activities is perceived as a risk, even assuming the connotations of a traumatic event, due to a sense of helplessness and inadequacy. These feelings as reported during the interviews with the patients, have been triggered by the loss of social support during lockdown due to the suspension of physical rehabilitation therapies or group therapies and were accentuated in patients perceiving their disease as unstable due to a recent starting/switching of DMT. A recent study reported more than 232 cases of COVID-19 infection among people with MS reported by Italian neurologists through a specifically designed web-based case report form (25) . Out of them, six were critical patients. These results must be considered only preliminary, also in the light of the speculations about the potentially protective role of some DMTs against COVID- 19(25) . Questions about the long-term effect of this pandemic on psychiatric comorbidities, as well as on the patient-physician relationship need further investigation. The study has some limitations. Firstly, the generalizability of the results, because of the response rate and the telephonic modality of administration that did not permit to recur to more extended and self-reported questionnaires. Despite the increased use of telephonic interviews in research, it is unknown whether they are as valid as diagnostic face-to-face interviews, so caution is required in assuming comparability of inperson and telephonic results of administered questionnaires. Furthermore, the response rate does not allow us to be sure of the reported percentages. A selection bias is possible; 35,7% of patients did not participate to the study. Among them, more than 25% did not answer to telephone during the short recruitment period; about the others (approximately 10%) refused the interview because they referred to have not enough time. We cannot be sure the real reason they refused the interview, if this was related to a mood disorder However, since the telephonic interviews were administered when RRMS patients had just returned to work during COVID-19 epidemic, they did not have recall bias about their mental state, and it is an important element in PTSD evaluation. In conclusion, MS patients, already burdened in physical and psychological terms, may be more vulnerable to the concerns and neuropsychiatric consequences related to COVID-19, also in the light of their awareness of being potentially more likely to contract infections. Considering the rapid spread of the disease, MS specialists should monitor MS patients for neuropsychiatric complications and implement strategies to offer psychological support when needed. 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