key: cord-328908-2004vp48
authors: Thombs, Brett D.; Kwakkenbos, Linda; Henry, Richard S.; Carrier, Marie-Eve; Patten, Scott; Harb, Sami; Bourgeault, Angelica; Tao, Lydia; Bartlett, Susan J.; Mouthon, Luc; Varga, John; Benedetti, Andrea
title: Changes in mental health symptoms from pre-COVID-19 to COVID-19 among participants with systemic sclerosis from four countries: A scleroderma patient-centered intervention network (SPIN) cohort study
date: 2020-10-03
journal: J Psychosom Res
DOI: 10.1016/j.jpsychores.2020.110262
sha: 
doc_id: 328908
cord_uid: 2004vp48

Introduction No studies have reported mental health symptom comparisons prior to and during COVID-19 in vulnerable medical populations. Objective To compare anxiety and depression symptoms among people with a pre-existing medical condition and factors associated with changes. Methods Pre-COVID-19 Scleroderma Patient-centered Intervention Network Cohort data were linked to COVID-19 data from April 2020. Multiple linear and logistic regression were used to assess factors associated with continuous change and ≥ 1 minimal clinically important difference (MCID) change for anxiety (PROMIS Anxiety 4a v1.0; MCID = 4.0) and depression (Patient Health Questionnaire-8; MCID = 3.0) symptoms, controlling for pre-COVID-19 levels. Results Mean anxiety symptoms increased 4.9 points (95% confidence interval [CI] 4.0 to 5.7). Depression symptom change was negligible (0.3 points; 95% CI -0.7 to 0.2). Compared to France (N = 159), adjusted anxiety symptom change scores were significantly higher in the United Kingdom (N = 50; 3.3 points, 95% CI 0.9 to 5.6), United States (N = 128; 2.5 points, 95% CI 0.7 to 4.2), and Canada (N = 98; 1.9 points, 95% CI 0.1 to 3.8). Odds of ≥1 MCID increase were 2.6 for the United Kingdom (95% CI 1.2 to 5.7) but not significant for the United States (1.6, 95% CI 0.9 to 2.9) or Canada (1.4, 95% CI 0.7 to 2.5). Older age and adequate financial resources were associated with less continuous anxiety increase. Employment and shorter time since diagnosis were associated with lower odds of a ≥ 1 MCID increase. Conclusions Anxiety symptoms, but not depression symptoms, increased dramatically during COVID-19 among people with a pre-existing medical condition.

The SARS-CoV-2 coronavirus disease (COVID-19) pandemic has caused more than 400,000 deaths and has had devastating health, social, political, and economic consequences worldwide. There are expected to be serious mental health implications during and beyond the initial outbreak, but their degree and nature are not well understood. [1] [2] Many cross-sectional studies report percentages of participants above cutoff thresholds on mental health symptom questionnaires during COVID-19. Such percentages, however, vary substantially across otherwise similar populations even in normal times. 3 Furthermore, they tend to dramatically overestimate prevalence obtained from validated methods, and there is too much heterogeneity to correct for differences statistically. 4, 5 Thus, studies that directly evaluate changes are needed.

Based on a living systematic review, 3, 6 as of June 22, 2020, only 5 studies had compared mental health prior to and during COVID-19. Four studies of university students suggest small increases in depression but minimal or no increases in anxiety. A United Kingdom general population study found small increases in general mental health symptoms but did not differentiate between anxiety and depression symptoms. No studies had evaluated mental health changes among people at risk of COVID-19 complications due to pre-existing medical conditions. Furthermore, despite important differences in pandemic responses across countries, no studies had compared mental health changes between countries.

People with the autoimmune disease systemic sclerosis (SSc; scleroderma) are representative of patients with pre-existing medical conditions that put them at risk during COVID-19. More than 40% have interstitial lung disease, many are frail, and use of immunosuppressant drugs is common. 7, 8 The Scleroderma Patient-centered Intervention Network (SPIN) Cohort routinely collects mental health outcomes at 3-to 6-month intervals. [8] [9] [10] The SPIN COVID-19 Cohort was initiated to collect data during COVID-19 and allows J o u r n a l P r e -p r o o f Journal Pre-proof comparison of mental health symptoms prior to and during COVID-19 for participants enrolled in both cohorts.

Our objective was to compare anxiety (PROMIS Anxiety 4a v1.0 scale 11, 12 ) and depression (Patient Health Questionnaire-8 13 ) symptoms before and after onset of COVID-19 among people with SSc, including (1) continuous score changes; (2) proportion with change scores of at least one minimal clinically important difference (MCID); (3) proportion initially under a cutoff threshold who changed by at least 1 MCID and reached the threshold; and (4) factors associated with changes, including country, comparing results from Canada, France, the United Kingdom, and the United States.

This was a longitudinal study that linked pre-COVID-19 data from the SPIN Cohort 8-10 to data collected from a sub-cohort during the baseline assessment of the associated SPIN COVID-19 Cohort between April 9, 2020 and April 27, 2020 using the same measurement scales. Person-level, deterministic linking was used with participant email addresses as the indentifier. The full protocol for the SPIN COVID-19 Cohort and the present study, which provides more detail on the methods and measures, is available online (https://osf.io/kbncx/). Anxiety Symptoms. The PROMIS Anxiety 4a v1.0 scale 11,12 includes 4 items asking participants, in the past 7 days, how often: (1) "I felt fearful"; (2) "I found it hard to focus on anything other than my anxiety"; (3) "My worries overwhelmed me"; and (4) "I felt uneasy". Items are scored 1-5 with response options "never" to "always". Higher scores represent more anxiety.

Possible raw scores range from 4 to 20. Raw scores are converted into T-scores standardized from the general US population (mean = 50, standard deviation = 10). A change of 4.0 T-score points was selected to represent the MCID 17 and a threshold for identifying people with at least moderate symptoms of T-score ≥ 60. 11 PROMIS Anxiety 4a v1.0 has been validated in SSc 18, 19 and is included in all 3-month SPIN Cohort assessments.

Depressive Symptoms. The eight-item PHQ-8 13 measures depressive symptoms over the last 2 weeks with item scores from 0 (not at all) to 3 (nearly every day) and higher scores representing more depression. Possible total scores range from 0 to 27. The MCID has been estimated to be 3.0 points, 20 and a threshold of ≥ 10 is commonly used to identify people who may have depression. 21 The PHQ-8, which is assessed every 6 months in the SPIN Cohort, performs equivalently to the PHQ-9, 22 which has been shown to be valid in SSc. 23

Descriptive statistics are presented as mean (standard deviation) for continuous variables and numbers (percentages) for categorical variables. Changes in anxiety and depression symptoms were described: (1) continuously with T-scores or raw scores, in terms of MCIDs, and with a Hedges g standardized mean difference effect size, all with 95% confidence intervals (CIs); (2) as the proportion of participants whose symptoms worsened or improved, separately, by at least 1 MCID, with 95% CIs; and (3) as the proportion initially below a T-score of 60 on the PROMIS Anxiety 4a v1.0 12 or a score of 10 on the PHQ-8 22 who increased by at least 1 MCID J o u r n a l P r e -p r o o f and reached the threshold score, with 95% CIs. For proportions, 95% CIs were generated based on Agresti and Coull's approximate method for binomial proportions. 24 We conducted two sets of sensitivity analyses for symptom changes. First, for both anxiety and depressive symptoms, we compared change to scores from assessments done months, have you seen any of the following health professionals to address a mental health concern?"), and financial resource adequacy (continuous).

All analyses were conducted using Stata (Version 13) with 2-sided statistical tests and p < 0.05 significance level.

Changes included exclusion of participants from Australia, because only 10 would have been eligible; removal of COVID-19 infection from model covariates, since only 4 participants reported a positive test; and addition of sensitivity analyses. Additionally, we controlled for baseline anxiety or depression symptom scores to ensure that factors associated with change were not confounded with initial symptom level differences.

The SPIN Patient Advisory Board (https://spinsclero.com) reviews all SPIN research, including the present study, and advises the SPIN Steering Committee to ensure that SPIN research addresses the needs of people with SSc. Additionally, members of the study-specific SPIN COVID-19 Patient Advisory Team was involved in each stage of the present study, including designing the SPIN COVID-19 Cohort, selecting outcomes for assessment, interpreting results, and providing comments on the present manuscript. 

As shown in Table 2 , anxiety symptoms increased more than a full MCID (4.9 points, 95% CI 4.0 to 5.7). Increases by country were 3.1 points (95% CI 1.7 to 4.6) for France, 4.4 points for Canada (95% CI 2.7 to 6.0), 6 Table 3 

As shown in Table 4 ).

We found that anxiety symptoms increased substantially compared to before the COVID-19 pandemic among vulnerable persons with a pre-existing medical condition, SSc, whereas depressive symptom changes were minimal. Overall, mean change on the PROMIS Anxiety 4a v1.0 was 4.9 points, greater than the MCID of 4 points. Approximately 50% of participants experienced an increase of  1 MCID. Results differed, however, by country. Anxiety symptoms increased by approximately 3 points among participants from France, 4 points among participants from Canada, 6 points among participants from the United Kingdom, and 7 points among participants from the United States. In multivariable analysis, compared to France, participants from the United Kingdom, United States, and Canada scored 3.3, 2.5, and 1.9 points higher. Participants from the United Kingdom also had odds of over twice as likely to have increased by  1 MCID. Overall, depression symptoms changed negligibly, but this was also associated with country with increases higher by approximately 2 points in the United Kingdom and 1 point in Canada and the United States, though this was not statistically significant for the United States. The only other variable that was consistently associated with symptoms of anxiety and depression was adequacy of financial resources, which was significantly associated with better outcomes for continuous anxiety symptoms and both continuous depression symptoms and odds of an increase in depression symptoms of  1 MCID.

Our study is one of the first to report mental health symptom changes during COVID-19 in a vulnerable population with a pre-existing medical condition and the first to compare symptom changes across countries. Compared to studies of university students, which suggest that depressive symptoms have increased by a small amount and anxiety minimally or not at all, 3, 6 we found that depressive symptoms changed minimally, but anxiety symptoms, on average, increased substantially. This may relate to the differential effect that COVID-19 is having on Increases in anxiety and depression symptoms were associated with country with large magnitudes in some cases. Comparing across countries is fraught with complexities. One possible explanation may relate to the coherence of governmental and civil responses in the countries we studied. Indeed, editorials in the Lancet have described the American response as "inconsistent and incoherent" 25 and the UK's national response as "astonishingly haphazard." 26 France undertook some of the most restrictive measures internationally to attempt to reduce the spread of the virus, 27 which may have reduced fear, relatively, among people vulnerable due to medical conditions. Canadian provinces were somewhat less restrictive but were generally consistent with a high level of political consensus on measures that have been taken. 28 The consistent finding that symptoms were associated with adequacy of financial resources to meet current needs underlines the financial implications of the pandemic and the role of economics in mental health. All of the countries with participants in our study have provided aid packages, 29-32 and findings from our study would seem to emphasize the importance of economic supports for those in need.

This is the first study to compare mental health outcomes among people vulnerable during COVID-19 due to a pre-existing medical condition. The SPIN Cohort is a well-characterized, ongoing cohort, and people with SSc are representative of other patient groups who are vulnerable during COVID-19. There are also limitations to consider. First, the SPIN Cohort is a convenience sample, although participant characteristics are similar to other large SSc cohorts. 8 Second, participants complete questionnaires online, which may reduce generalizability. Third, it J o u r n a l P r e -p r o o f Journal Pre-proof was not possible to capture and include local variables, such as the degree participants' communities were affected or whether public health interventions were consistently followed in those communities. Nonetheless, data were collected at a time when social isolations were generally at their most conservative. Finally, different MCID values may be chosen. The 4-point MCID we used for anxiety symptoms was conservative; others have recommended MCIDs of 2 to 3 points, 33 and it is possible that we may have underestimated the degree of patient-important change.

In sum, we compared mental health symptoms prior to and during the COVID-19 outbreak among people vulnerable due to a pre-existing medical condition. We found that anxiety symptoms increased substantially and that the magnitude was associated with country;

increases were highest in the United States and United Kingdom and more moderate in France and Canada. There were minimal differences in depressive symptoms during COVID-19 compared to pre-COVID-19. These findings, which differ from early reports of results from younger adults, for instance, and suggest that the nature of mental health implications for different populations may reflect specific concerns in COVID-19; however, more research is needed on this topic. J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f Figure 1 

The psychological effects of quarantining a city

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