key: cord-0910321-ntn4rw7h
authors: Alschuler, Kevin N.; Roberts, Michelle K.; Herring, Tracy E.; Ehde, Dawn M.
title: Distress and risk perception in people living with multiple sclerosis during the early phase of the COVID-19 pandemic
date: 2020-11-05
journal: Mult Scler Relat Disord
DOI: 10.1016/j.msard.2020.102618
sha: 5b7374b71496bae4192221d69ec7228c61a73d8e
doc_id: 910321
cord_uid: ntn4rw7h

BACKGROUND: : People living with MS during COVID-19 are experiencing the disruptions of the pandemic and concerns that their health status may place them at greater risk for worse COVID-19 outcomes. OBJECTIVE: : This study sought to understand how people living with MS in the United States experienced distress and perceived their COVID-19-related risk during the first surge of the pandemic. METHODS: : This was a web-based, self-report survey of people with MS who were living in the United States during the early stage of COVID-19. Primary outcomes were depression, anxiety, and positive-affect and well-being. Participants (N = 491) also provided data on demographics, MS-related factors, COVID-19 factors, and psychological coping. RESULTS: : Psychological distress was associated with age, psychological coping strategies, and having had symptoms consistent with COVID-19, but not with MS disease-related variables and COVID-19 risk factors. Perception of COVID-19-related risk was associated with age, MS disease severity, COVID-19-related factors, and anxiety. CONCLUSION: : This study demonstrated that even during COVID-19, distress and risk perception are primarily driven by psychological factors, experiencing symptoms consistent with COVID-19 and age, with minimal contribution from individual differences in health status, providing an impetus for continued efforts to optimize psychological interventions for people living with MS.

The emergence of the novel coronavirus disease 2019 was met with heightened concern in the multiple sclerosis (MS) community given the potential increased risk posed by disease-modifying therapy-associated immunosuppression, (1) (2) (3) as well as the fact that people with MS experience higher rates of comorbidities and are more likely to live in care facilities than the general population.(4-6) Concerningly, many of these factors, such as being immunocompromised or immunosuppressed due to their disease modifying therapies or having comorbidities such as heart disease or obesity, map onto the Centers for Disease Control and Prevention's (CDC) initial (and subsequently revised) list of COVID-19 risk factors (7) . * Many people are experiencing heightened distress in the setting of COVID-19.(10) While factors such as age or health status may shape how individuals perceive the threat of the virus, research on prior public health crises has also implicated psychological factors as central to pandemic-related distress. During the H1N1 pandemic, individuals who were less tolerant of uncertainty were more anxious, (11) and individuals were likely to minimize or underestimate their personal risk until they knew somebody who had contracted the virus, at which point their perception of risk rose. (12) * At the time individuals participated in this study there was no empirical research on the extent to which MSrelated variables (health status and/or disease-modifying therapies) impacted COVID-19 risk. We recognize that in the months since this study was conducted, emerging empirical research has suggested that the effect of these MS-related variables is less clear. (8, 9) However, the limited information available at the time of the study -and, thus, the context within which individuals assessed their personal situation -was that MS-related factors, at least in terms of certain disease-modifying therapies, may place an individual at greater risk. (1) (2) (3) A small body of literature has emerged examining distress among people living with MS during COVID-19. Three studies reassessed participants who had participated in trials prior to the pandemic to examine the extent to which distress changed over the studied interval. These studies produced mixed results, suggesting no or modest changes in anxiety or depression. (13) (14) (15) These studies had the advantage of pre-pandemic data to use as a baseline comparator, but were run on small samples (e.g., N = 67 (13) ) with restricted characteristics (e.g., only relapsing-remitting MS(14) or only progressive MS (15) ) due to the inclusion criteria of the trials from which they were drawn. In addition to those distress-focused studies, a large survey study on the healthcare impact of COVID-19 noted that "[p]articipants believed COVID-19 presents a major danger to their health and reported being generally highly worried about the disease." (16) There is a need to expand this line of research to better inform the deployment of psychological interventions. In particular, there is a need to understand the complex relationship of demographic factors, MS disease-related factors, COVID-19-related factors, and modifiable psychological factors with distress during COVID-19. Given that many of these factors are fixed and/or unmodifiable, it is particularly important to understand the role of modifiable psychological factors, such as mindfulness (17) , intolerance of uncertainty (18) , optimism (19) , loneliness (20) , and resilience (21) , that are the core targets of empirically-supported psychological interventions that have been shown to reduce distress in people living with MS (22) (23) (24) (25) (26) (27) .

The purpose of this study was to understand how people living with MS in the United States (US) experienced distress and perceived their personal risk of COVID-19 during April and May 2020, the period during which (a) the least was known about the virus, creating the most uncertain situation; (b) the initial spike in cases, hospitalizations, and deaths occurred; and (c) the first significant public health measures were implemented.

Within this context, we aimed to (1) describe the level of distress experienced by people with MS during the initial phase of the pandemic; (2) describe the extent to which people with MS perceived themselves to be at risk for contracting and/or dying from COVID-19;

(3) understand the extent to which demographic, MS disease and treatment-related, COVID-19-related, psychological, and social factors are associated with distress; and (4) understand the extent to which distress is associated with a person's perception of their risk for contracting and/or dying from COVID-19.

We developed a cross-sectional online survey in April 2020 to assess how individuals were responding to the emerging COVID-19 pandemic. Participation was open to individuals >18 years old who could read English and were in the US at some point on or after January 20, 2020, the date of the first identified COVID-19 case in the US. We targeted part of our recruitment specifically to individuals with a self-reported MS diagnosis. Participants were invited to complete the survey through emailed newsletters disseminated by the University of Washington (UW), as well as other online sources, including social media, the study team's website, and research recruitment websites or registries (ParticipateinResearch.org and researchmatch.org). A link to the survey was also posted publicly on the National MS Society's (NMSS) COVID-19 research webpage and in their emails highlighting COVID-19 research opportunities. Our goal was to capture a convenience sample of approximately N = 500 to give adequate power for the planned statistical analyses. (28) Data were collected 4/10/20 to 5/26/20, the period of the most restrictive public health measures to date. Participants who followed the link to the study were taken to the survey on the REDCap (Research Electronic Data Capture) platform, a secure, HIPAA-compliant, password protected web-based data platform hosted by UW (29) . To prevent responses from bots, respondents had to engage with a human verification service (reCAPTCHA). The first page of the survey was an information statement that provided standard informed consent information. Participants indicated their consent by proceeding with the survey, which included the measures described below. Participants were not compensated for participation in the study. This study's procedures were approved by the UW Human Subjects Division. Each of these measures has been fully validated and demonstrates sound psychometrics (38) (39) (40) (41) (42) .

The measures of mindfulness, intolerance of uncertainty, and optimism have each also been previously used in studies of people living with MS (23, 43, 44) , and the resilience scale was calibrated in part on people with chronic illnesses, including MS (42) .

Prior to testing the study hypotheses, the data were inspected for duplicates, missing data, and outlier variables. All responses were verified for validity by cross-checking participants' identifiable information (e.g., name, phone number, email address). Where duplicate responses were identified, the first complete survey response was retained.

Survey completion time was reviewed in order to identify any surveys in which participants completed the questionnaire faster than a human could read, which did not result in removal of any participants. There was very little missing data, primarily limited to individuals who stopped participation without fully completing the survey. In total, we Preliminary analyses were then conducted to ensure that study data met the assumptions for the planned analyses, including verifying that there was no evidence for significant skew, kurtosis, or heteroscedasticity. This revealed that the vast majority of the variables were appropriate for the planned analyses, with two primary exceptions: (1) consistent with samples reported in prior studies of people with MS, the sample overwhelmingly identified as white, with insufficient numbers of individuals distributed across the other racial categories to conduct meaningful analyses and (2) there were very few individuals who had received a COVID-19 test or tested positive for COVID-19 during the study period.

Thus, we were unable to include these variables in the study analyses.

To describe the study sample and address the first two study aims, we ran descriptive analyses yielding means and standard deviations or frequency counts with percentages, as appropriate. The third aim, examining biospsychosocial factors associated with distress, was addressed through a series of stepwise multiple regression analyses that predicted three outcomes: anxiety, depression, and positive affect and well-being. Each analysis was conducted using the same model, with the outcome predicted by participant demographics (age and gender) in the first step, MS disease-related variables (disease course and level of disability) in the second step, COVID-19 factors (CDC-defined risk factors, DMT-associated risk factors, and the presence of COVID-19 symptoms) in the third step, and psychological variables (mindfulness, intolerance of uncertainty, optimism, resilience, loneliness) in the fourth step. Similarly, the fourth aim, examining the extent to which distress was associated with risk perception, was analyzed through two more multiple regression analyses that predicted perceived risk of contracting COVID-19, and perceived risk of dying from COVID-19. In these two regressions, the first three steps were identical to that of aim three, while distress (depression, anxiety, and positive affect and well-being) was in the fourth step.

Participants with MS who provided complete data (n = 491) are described in Table 1 Descriptive data for the primary variables are reported in Table 3 was significantly associated with higher depressive symptom severity, accounting for 6.6% of the variance in depression. In step 2, worse MS disease severity was associated with higher depressive symptom severity (β = 0.12, p<0.05), accounting for 1.5% of the variance. Rates of distress in this study were aligned with the other studies published on distress in the MS population during COVID-19.(13-15) Both depression and anxiety were elevated above the rates observed in the general population, but only marginally above typical levels for the MS population relative to prior studies.(35) Anxiety was slightly more elevated and more prevalent than depression in our participants. Both were associated with being younger, less mindful, more intolerant of uncertainty, less optimistic, lonelier, and less resilient. While having more COVID-19 risk factors were not associated with greater distress, it is notable that having had symptoms consistent with COVID-19 that could not be explained by another medical condition was associated with greater distress. It is undoubtedly the case that having COVID-19 symptoms increases distress because it makes the threat more apparent or real. Moreover, given the high level of concern about COVID-19 that was reported in another large survey of people living with MS (16) and the admission that fears of the severity and contagiousness of COVID-19 is the most common COVID-19 associated stressor in a general population sample (45) , it may be the case that individuals are primed to experience increased distress when evidence of the threat is more apparent. Many of the other factors that were found to be associated with distress are also potentially influenced directly or indirectly by the pandemic. For example, younger participants were more distressed; they may be the age group most likely managing the demands of both work (e.g., working remotely, being laid off or furloughed) and family obligations (e.g., lack of childcare) and may experience more disruptions or stressors. The added challenge of COVID-19 also likely impacts the psychological domains implicated in the study's analyses. In parallel to findings in the general population, (46) COVID-19 has increased social isolation and, not surprisingly, we observed a relationship between loneliness and distress. It is also possible that the restrictions and economic, social, and physical challenges imposed by the pandemic may interfere with the ability to remain mindful, cope with uncertainty, or remain optimistic, each of which was also associated with distress.

Interestingly, the models for perceived risk of contracting and/or dying from COVID-19 demonstrated less parallelism than the distress models. In both models, anxiety was a strong predictor of risk perception, which is not surprising, as one byproduct of heightened anxiety is a greater sensitivity to threatening health information both during pandemics (11) and while living with MS(47), including a higher perceived risk of negative outcomes. However, the two models differed significantly in the contribution of MS disease-related and COVID-19-related factors to risk perception. In the case of perceived risk of contracting COVID-19, having had symptoms consistent with COVID-19 that could not be explained by another medical condition as the strongest predictor of risk perception.

As referenced previously, this finding is consistent with research from other pandemics that suggests that the increased presence of the virus in an individual's world (such as when it is contracted by someone an individual knows (12) Regardless of the extent to which distress is different from the pre-COVID-19 era, the levels of distress observed in this population are concerning, particularly due to their association with quality of life, disability, and adherence.(48) While distress was not strongly associated with MS or COVID-19-related risk factors, it was guided most notably by coping, such that those who coped in a healthier or adaptive manner experienced less distress.

This serves as an important reminder to providers to assess for distress in their patient populations and make appropriate referrals to optimize the ways in which patients deploy coping strategies. It appears likely that this can be addressed through existing evidencebased psychotherapies, such as mindfulness or acceptance-based approaches to target mindfulness and intolerance of uncertainty, social engagement targeted through cognitivebehavioral therapy to reduce loneliness, and positive psychology interventions that facilitate resilience and optimism. (22) (23) (24) (25) (26) (27) The rapid implementation and increased insurance coverage of telehealth interventions as a result of the pandemic (49) may facilitate access to these treatments in the MS population. Thus, there is promise for these existing interventions to be useful in the present circumstance, with the important caveat that they must be adapted to the current context (e.g., life during COVID-19). Further research is needed to demonstrate that these existing interventions can be tailored appropriately and are effective for this purpose.

This study has limitations. First, data were collected on a convenience sample. Descriptive data were notable for participants being healthier and less disabled than the MS population at large, suggesting that the sample does not fully represent the MS population. Geographic distribution included an overrepresentation of individuals from Washington state, as we had greater access to potential participants due to our research program existing in that region. Second, data were collected via self-report which, while appropriate for measuring these constructs, represents participants' perceptions. In this context, it is important to note that the presence of a physician-confirmed MS diagnosis was self-reported and was not independently verified. Third, the results need to be interpreted in context: the study was conducted in an early phase of the pandemic and how people experience and understand COVID-19 continues to evolve.

In summary, the COVID-19 pandemic has served as a unique threat to the health and wellbeing of the world's population, with extra concern for the impact on vulnerable populations. This includes people with MS who live with more comorbidities and worse health status than the general population. Approximately half of this study's participants experience clinically significant levels of depression and/or anxiety, and their distress is impacted primarily by their use of modifiable coping strategies. As the pandemic continues, the associated need to address the impact on mental health, distress, and wellbeing continues to grow. Further research is needed on the adaptation and implementation of empirically supported approaches for improving on this distress.

This study was partially supported by the Nancy and Buster Alvord Endowed Professorship 

The authors declare no conflicts of interest

This study was partially supported by the Nancy and Buster Alvord Endowed Professorship 

The Authors declare that there are no conflicts of interest. Note. * Clinical cutoff was calculated based on being one standard deviation from the mean in the "worse direction" (e.g., more depressed, more anxious, less positive affect; T > 60 for depression and anxiety, T < 40 for positive affect and well-being), which is consistent with studies that have analyzed the association of PROMIS scores with measures with established clinical cutoffs. (50, 51) 

pandemic and the use of MS disease-modifying therapies

Rethinking high-risk groups in COVID-19

Multiple sclerosis and the risk of infection: considerations in the threat of the novel coronavirus, COVID-19/SARS-CoV-2

Emerging effects of comorbidities on multiple sclerosis

Cumulative impact of comorbidity on quality of life in MS

People Who Are at Higher Risk for Severe Illness

Italian Study Group on C-iims. An Italian programme for COVID-19 infection in multiple sclerosis

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

Multidisciplinary research priorities for the COVID-19 pandemic: a call for action for mental health science

Intolerance of uncertainty, appraisals, coping, and anxiety: The case of the 2009 H1N1 pandemic

H1N1 Influenza Pandemic: the role of threat, coping, and media trust on vaccination intentions in Canada

Psychological consequences of COVID-19 pandemic in Italian MS patients: signs of resilience?

Psychological status of patients with relapsing-remitting multiple sclerosis during coronavirus disease-2019 outbreak

The emotional impact of the COVID-19 pandemic on individuals with progressive multiple sclerosis

Pandemic on the Health Care of> 1,000 People Living with Multiple Sclerosis: A crosssectional study

Examining trait mindfulness, emotion dysregulation, and quality of life in multiple sclerosis

Intolerance of Uncertainty: Shaping an Agenda for Research on Coping with Multiple Sclerosis

An exploration of the relationship between perception of control, physical disability, optimism, self-efficacy and hopelessness in multiple sclerosis

Accuracy and precision of smartphone applications and commercially available motion sensors in multiple sclerosis

The mediating role of resilience on quality of life in individuals with multiple sclerosis: A structural equation modeling approach

Feasibility trial of telehealth support group participation to reduce loneliness in multiple sclerosis

Pilot intervention to promote tolerance for uncertainty in early multiple sclerosis

Promoting resilience in individuals aging with multiple sclerosis: Results from a pilot randomized controlled trial

Mindfulness training for emotion dysregulation in multiple sclerosis: A pilot randomized controlled trial

Behavioral Interventions in Multiple Sclerosis

Telephone-based physical activity counseling for major depression in people with multiple sclerosis

A power primer

Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support

The Patient-Reported Outcomes Measurement Information System (PROMIS): progress of an NIH Roadmap cooperative group during its first two years

Development of physical and mental health summary scores from the patient-reported outcomes measurement information system (PROMIS) global items

The Patient-Reported Outcomes Measurement Information System (PROMIS) developed and tested its first wave of adult self-reported health outcome item banks

The neurology quality-of-life measurement initiative

Validating Neuro-QoL short forms and targeted scales with people who have multiple sclerosis

People with multiple sclerosis report significantly worse symptoms and health related quality of life than the US general population as measured by PROMIS and NeuroQoL outcome measures

Emotions and preventive health behavior: worry, regret, and influenza vaccination

Validation of patient determined disease steps (PDDS) scale scores in persons with multiple sclerosis

Construct validity of the five facet mindfulness questionnaire in meditating and nonmeditating samples

Fearing the unknown: a short version of the Intolerance of Uncertainty Scale

Distinguishing optimism from neuroticism (and trait anxiety, self-mastery, and self-esteem): a reevaluation of the Life Orientation Test

Measuring social health in the patient-reported outcomes measurement information system (PROMIS): item bank development and testing

Development of a resilience item bank and short forms

Perceived stress in multiple sclerosis: the potential role of mindfulness in health and well-being

Improving the quality of life and psychological well-being of recently diagnosed multiple sclerosis patients: preliminary evaluation of a group-based cognitive behavioral intervention

COVID-19 Stress, Coping, and Adherence to CDC Guidelines

Three Months of

Loneliness During the COVID-19 Lockdown

Perception of prognostic risk in patients with multiple sclerosis: the relationship with anxiety, depression, and disease-related distress

Mental health comorbidity in MS: depression, anxiety, and bipolar disorder

Early outpatient experiences and implications for the future

A comparison of multiple patient reported outcome measures in identifying major depressive disorder in people with multiple sclerosis

Establishing a common metric for selfreported anxiety: linking the MASQ, PANAS, and GAD-7 to PROMIS Anxiety