Fragiles but Resilient. The Key Strategies to Cope with Pandemic in Persons with Multiple Sclerosis. A Controlled Web Survey

Multiple Sclerosis (MS) is a chronic, autoimmune, inflammatory and neurodegenerative disease that predominantly affects young individuals, between the ages of 20 and 50, mostly female ¹. People with MS (pwMS) present a high burden of neuropsychiatric comorbidities, such as anxiety and depression (A/D) ², also associated with fatigue, physical symptoms and cognitive disability, resulting in a lower quality of life and decreased compliance. These conditions are associated with psychological stress and could be responsible of the disease exacerbation ³.

On February 21st, 2020 the first cases of SARS-CoV-2 infection were diagnosed in Italy and on March 11th, eighteen days after, the World Health Organization declared that the infection had become pandemic. Pandemic represents a sudden and major threat to health, that is an unexpected psychological stress, worsened by the general “lockdown” (the necessary severe restrictions on daily life were decided from March 10th, to May 3rd). The phantom of viral infection, the sudden psychosocial changes, the announced economic consequences and the confusing and alarmist information led people to fear and fear can increases anxiety and mental distress, also worsening psychiatric symptoms ⁴. People with autoimmune and inflammatory diseases, or treated with immunosuppressive therapy, were immediately considered at a major risk of harmful infection ⁵. As a precaution, researchers and clinicians payed a great attention to these groups of patients.

Obviously, pwMS are part of the fragile population but, from a psychological point of view, this means that they are paradoxically more used to manage a chronic but unpredictable condition compared to healthy people. Especially in the initial stages of the diagnostic and therapeutic path for MS, and then for relapses, they suffer a forced suspension of their routine habits and professional life (due to the symptoms and the medical visits). Similarly, the SARS-CoV-2 pandemic and the restrictions did the same on the general population. In fact, a great and serious impact on mental human health was described as a result of actual and past pandemics, particularly involving vulnerable groups: older adults, the immunocompromised, subjects with previous clinical and psychiatric conditions, but also relatives of infected patients, residents of high-incidence areas, quarantined people and health professionals, going beyond the division between healthy/diseased people ^{4, 6}.

How did this higher risk of infection impact on the psychological status of pwMS during the restrictions? Could the concern for health and for MS, considered as an adjunctive risk factor for SARS-CoV-2 poor prognosis, have stressed the pwMS or have motivated them to better tolerate the lockdown? Moreover, might the pwMS have gained greater resilience to lockdown compared to the general population?

We conducted a study to observe the psychological reaction of pwMS during the SARS-CoV-2 emergency. We considered A/D symptoms to find out possible patterns among lifestyle factors and psychological distress. These findings could address the clinical interview and suggest both the critical areas to be supported and the strengths to be promoted. We also collected the same data from volunteers non affected by MS (controls) to compare their answers with those of the fragile MS population.

The primary outcome concerned the rates of anxiety and depression scores in pwMS compared with controls.

The secondary objectives considered the effects of anamnestic and lifestyle factors on A/D. Resilience of pwMS, already studied for adaptation to MS, was also explored in this setting.

The study design was observational, controlled, based on a web survey, and focused on improvement of quality of the clinical practice. It was approved by the Ethic Committee “Milano Area 3” and conducted at Niguarda Hospital according to the Good Clinical Practice and the Declaration of Helsinki. Personal data have been collected and analyzed in pseudo-anonymous and aggregate form, according to regulation 679/2016 EU.

All subjects were informed on the aim of the study and provided the informed consent. PwMS were enrolled according to the following criteria: adult subjects diagnosed with Multiple Sclerosis ⁷ who have indicated a valid email address to be contacted by the Niguarda MS Center. Controls were invited to participate using WhatsApp ^tm viral message in four different towns besides the city of Milano to involve the northern, central and southern regions of Italy and according to the following eligibility criteria: adult subjects not diagnosed with MS and not working as health professionals.

All data have been validated and then submitted to usual descriptive statistics. Binary and nominal categorical variables have been described with relative and absolute frequency tables, while continuous and ordinal variables have been described as mean and standard deviation or median and range, depending on their distribution, checked by the Shapiro-Francia test. Comparison between nominal and binary variables were carried out by the Fisher's exact test, whereas comparisons between continuous variables were done with the Student's t test, the Welch's test, or with the Mann-Whitney U test with exact algorithm, depending on their distribution and on the homogeneity of variances. Comparisons between ordinal variables were always carried out by the exact Mann-Whitney U test.

Correlations between variables were calculated using the Pearson's r, or the Spearman's ρ, again, depending on the distribution.

On April 10th 2020, a total number of 165 pwMS followed up by the MS Center of the Niguarda hospital in Milan, received by email an invitation to join the study by filling out a web survey. The survey was built using Google Form, a platform by Google LLC. The study collected the answers about lifestyle, habits and psychological status referred to the two weeks from March 27 to April 10.

The web survey provided five sections totally reported in the Supplementary Table 4A the first included the study and the privacy disclosures with the consent. The second section contained multiple choice questions about: socio-demographics, MS anamnestic data and ongoing treatment, previous history of anxiety and depression with related treatment, satisfaction with the information received by the MS Center, changes in MS treatment. The third section referred to the health perception, the need for economic or logistic support and the lifestyle habits during the SARS-CoV-2 restrictions. These last were: the everyday life coping strategies, the home and the family relationships, the physical activities, the job changes, the impact of media news. The fourth section investigated: the feared or objective SARS-CoV-2 symptoms, the mourning of relatives, friends or neighbors caused by the virus. The final section consisted of two structured self administered questionnaires: “The 7-items Generalized Anxiety Disorder Scale” (GAD-7) ⁸ for anxiety and “The Patient Health Questionnaire” (PHQ-9) ⁹ for depression. Both of these brief screenings were based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) (DSM-IV-TR) ¹⁰, respectively for the General Anxiety Disease and for the Major Depressive Episode. The items had response options ranging from 0 to 3 (0=Not at all; 1=Several days; 2=More than half the days; 3=Nearly every day) with higher scores indicating more severe symptoms.

The GAD-7 has a sum score ranging from 0 to 21. This measure was validated in the general population ⁹ and in other specific populations, including in MS for clinical and research purposes ¹². A cut point of 10 or greater provided sensitivity and specificity higher than 0.80 ⁸ .

The PHQ-9 includes nine items with a sum score ranging from 0 to 27; it’s commonly used for screening and diagnosis of depression also in pwMS ¹³. A cut-off score greater than or equal to 10 has been suggested as indicative of significant depressive symptoms ¹⁴ and it has also been considered a suitable screening tool to measure depression in pwMS.

The study received a good feedback by pwMS and the web survey represented a very useful tool, as other examples of telemedicine, in an outstanding period of restrictions ¹⁶. Despite the possible selection bias due to the voluntary enrollment, socio-demographic characteristics didn’t differ between groups and this was a favorable element which encouraged us to proceed with the comparison. Moreover, the geographical distribution of the sample didn’t determine a significant difference in the perception of SARS-CoV-2 related variables, as reported in other studies ^{17, 18}, allowing us to consider the sample as a whole.

A/D rate in pwMS proved comparable with the results of other Italian surveys conducted during the SARS-CoV-2 lockdown even if collected with different questionnaires. Considering the clinical cut-off, Capuano ¹⁹ reported a similar rate of 16.4% for anxiety, evaluated with the State section of the State-Trait Anxiety Inventory, and a lower rate of 11.9% for depression, evaluated with the Beck Depression Inventory II (BDII>18).

Regarding the severity class of A/D symptoms, Zanghì ¹⁸ according to the Depression, Anxiety and Stress Scale, reported comparable data with a rate of 42.1% for mild/moderate anxiety class and a rate of 44.4% for mild/moderate depression class (Table 3).

Moreover we must consider that the results of psychological assessment might be influenced by the specific questionnaire administered and that we collected an emotional snapshot of the acute phase of the pandemic, without a follow up to check the evolution of the psychological reaction over time. For these reasons we decided to consider the PHQ-9 and GAD-7 normative data referred to pwMS and to the general population as additional control for each group.

Regarding the PHQ-9 tool, our findings (Table 3) are consistent with pwMS literature data collected before the pandemic; in fact Terrill ²¹ reported a mean score of 7.5 (5.5) point in 513 pwMS, and Amtmann ¹⁴ detected a mean score of 6.6 points in 455 pwMS with the following rate of depression for each frequency class: minimal = 42.4%; mild=33.2%; moderate=16.3%; severe=8.1%.

The PHQ-9 normative data in the general population shows a prevalence rate of moderate to high severity of depressive symptoms of 5.6% with a mean range of 2.9 (3.5) ²² while in our data controls reported three times higher scores.

Literature data concerning GAD-7 indicate a rate of 6.2% in the general population ²³ with a mean score of 2.95 (3.3) ²² that are twice as much compared to our data in controls. Korostil ²⁵ reported the rate of 19% in pwMS which is similar to our results.

In summary, A/D findings were similar to the published pre-pandemic data for pwMS and higher for the controls, considering pwMS and the normative data. These findings support the hypothesis that the psychological reaction of pwMS in the first period of lockdown was limited. In fact the A/D scores were not higher compared to the expected in pwMS. On the contrary the controls showed higher values than the normative ones, suggesting an acute psychological reaction. Maybe that PwMS mainly concentrated on the psychological reactions to the SARS-CoV-2 pandemic, dissociating the MS, also because the questions were not referred, as usual, only and specifically to the MS perception. Despite this possible limitation, the central role of MS in thoughts and emotions of pwMS is underlined by the answers about the health concern, by the coping strategies and by the importance of the correlation with A/D as described below and overall reported in Supplementary Table 2A. Furthermore we placed the A/D brief screening questionnaire at the end of the survey with the indication to consider the psychological state in general.

Looking at the variables studied, first of all health perception, pwMS considered themselves at higher risk for the infection, upon advice from experts and new regulatory norms, showing more caution and fear to go outside. So they might have been more resilient to tolerate the restrictions and the cohabiting relatives. When a suspect of infection occurred, PwMS tended to show lower A/D symptoms than controls.

The correlation between health themes and the psychological reaction resulted closer in controls, suggesting that the pandemic was the main trigger for them, while in pwMS other factors might be involved, first of all MS. Nevertheless pwMS with recent MS diagnosis, supposedly being more used to tolerate the change of daily habits, didn’t show more resilience in terms of lower A/D score. In a larger study ²⁶ that share with us the relevant role of the personal coping to bear the lockdown, the time since diagnosis with other factors as gender, antidepressant, living arrangements or employment status didn't predict a impact of the pandemic on the personal life.

About daily life, most of the coping strategies were common in both groups. Staying active and focused on practical tasks resulted in the best adaptive strategy, being more effective in this fragile population, as reported in a similar Italian study and in the previously cited international survey ^{18, 26}.

Despite this, pwMS selected more frequently some maladaptive strategies: they were more used to think about health, to continue by video calls the usual activities and to keep in contact by phone with relatives and friends, even if this increased anxiety (Figure 2). These daily habits should be inquired and supported during the clinical visits.

Media news showed an important and negative impact on A/D. PwMS reported to listen to the news more frequently compared to the controls but, even if they considered the news reliable and useful to keep on respecting the lockdown, these considerations didn’t affect their psychological status while the doubts on reliability of news increased anxiety in controls (Figure 1).

According with other studies the physical activity ²⁷, the MS duration and employment status ²⁶ were not associated with the psychological reaction during the lockdown. Job by itself is a vexed theme for pwMS ²⁸ and represents a primary source of stress. Maybe for this reason the A/D scores were not associated with the actual changes in working habits, as happened for controls.

Despite the small sample and the possible selection bias due to the voluntary enrollment, these results might suggest that pwMS showed a proper psychological resilience during the first acute phase of the SARS-CoV-2 pandemic. They respected the restrictions more easily, being more aware of the priority of health. However, they tended more often to use phone and video calls and to focus on the media news and on health concerns, fueling A/D. Clinicians should pay attention to enquire about these specific maladaptive strategies considering the chance of a specific psychological intervention to support them in the different phases of the pandemic.

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