Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis of the skin and internal organs and vasculopathy, leading to severe physical damage.9 A state of psychological frailty was particularly found in people with chronic conditions during the COVID-19 pandemic,10 including patients with SSc. In such a population, a significant increase in symptoms of anxiety, but not depression compared to before the onset of the COVID-19 pandemic, is inversely related to the adequacy of financial resources.11 Another critical consideration for this population is fear due to COVID-19, as reported in a cohort of SSc patients from the United States, Canada, France, and the United Kingdom (UK) via a validated questionnaire.12 Higher levels of COVID-19-related fear were found in SSc patients in the United Kingdom and were associated with low financial intake and prior anxiety status.13 Fear of the pandemic was described by patients as the main cause of missed outpatient visits, as found in a telesurvey of the Indian Progressive System Sclerosis Registry.14 For patients with SSc, diligent follow-up is essential to prevent or limit multiorgan involvement of the disease through appropriate diagnostic and therapeutic tools to achieve a better disease outcome.15 Anxiety and fear due to COVID-19 thus emerged as signs of psychological fragility in SSc patients during the current pandemic. Therefore, the aim of the present paper is to assess their prevalence in SSc patients during the second and third waves of the SARS-CoV-2 pandemic in Italy using validated questionnaires and to investigate possible associated factors.
Materials and methods
We performed a cohort study of 114 consecutive patients with SSc referred to the Scleroderma Clinic of the Policlinico Umberto I in Rome, Italy. During the period from October 2020 to March 2021, a new rise in the RT index (the average number of new infections caused by a single infected person at time t in the susceptible population16) was recorded and stricter containment measures were implemented.17 We chose 28 patients who had not attended the scheduled examination and 86 subjects who had made regular visits to outpatient clinics during the same period, according to gender and age. Both groups were administered (by phone or in person, respectively) the Generalized Anxiety Disorder Scale-7 (GAD-7), used in patients with pre-existing medical conditions during the COVID-19 pandemic, and the COVID-19 Fear Questionnaire for Chronic Medical Conditions (Fears of COVID-19), developed and validated in SSc patients of the Patient-Centered Intervention Network (SPIN) COVID-19 cohort study.12,18,19 The GAD-7 is a 7-item scale benchmark score from 0 to 3 in all questions. It investigates how often the patient has been bothered by seven different anxiety symptoms in the past 2 weeks with response options such as “not at all,” “several days,” “more than half the days,” and “almost every day” scored. as 0, 1, 2 and 3, respectively. Scores of 5, 10, and 15 are taken as cut-off points for mild, moderate, and severe anxiety, respectively. A score of 8 or more points is a reasonable value for the need for further assessment to determine the presence and type of anxiety disorder.18 The GAD-7 has been found to have excellent psychometric properties and is short and easy to administer19 (Table 1 ) . Fears of COVID-19 is a 10-item scale measure that assesses fears related to the pandemic among vulnerable patients due to pre-existing illnesses. It assesses fears of social isolation, adequate care for chronic conditions during the pandemic, greater risk of complications of COVID-19 due to medical conditions, and fear of contracting COVID-19 (Table 2).12 Finally, an analysis of potential factors that were associated with higher questionnaire scores in patients who did not have outpatient follow-up, such as age, patient-reported disease activity, ongoing treatment for anxiety/depression, current work status, and living alone.12 This study complies with the Declaration of Helsinki. The ethics committee of the Sapienza University of Rome – Policlinico Umberto I approved (institutional review board approval no. 6364) the study and informed consent was obtained from the subjects. Table 1 Generalized anxiety disorder-7 (GAD-7) questionnaire. Table 2 10-item COVID-19 Fears of Chronic Medical Conditions Questionnaire (Fears of COVID-19), validated in the MS patient population
Statistical analysis
Statistical analysis of the result was performed using GraphPad Prism 8 for Windows. Qualitative variables were described as frequencies and percentages, continuous variables as medians and interquartile ranges, and assessed by chi-square test (χ2 test) and Fisher’s exact test, as appropriate. Paired or unpaired Mann-Whitney test was used to compare ordinal values between independent sample. Multivariate linear regression analysis was used to adjust the association between a continuous dependent variable and the independent variables for potential confounders.
Results
The study population consisted of 114 consecutive patients with SSc. Of the 28 patients who had no outpatient visits during the selected period, 27 were female and the median age [quartiles] it was 64 [55.25;70] years. Among 86 patients who had regular follow-up, 78 were women and the median age was [quartiles] it was 60 [61.5;67] years. The first group had statistically significantly more patients with a score ≥8 on the GAD-7 questionnaire (22/78.6% vs. 16/18.6%, p<0.0001) and recorded higher scores on both the GAD-7 (median [quartiles] 10.5 [8.25;14] against 4 [0;7]p<0.0001) and fears of COVID-19 (median [quartiles] 31.5 [26.25;37.25] against 20 [13.75;28], p<0.0001) than the second group. More patients in the participating group reported worsening of SSc symptoms than patients in the absent group (26/30.3% vs. 3/10.7, p=0.0039) (Table 3). In multivariate analysis performed on patients in the absent group, lack of work and ongoing treatment for anxiety/depression showed a significant association with GAD-7 (p=0.0275 and p=0.0188) and the fear of COVID score -19 (p=0.0016 and p=0.0099 ) (Tables 4 and 5). Multivariate analysis performed on all 114 patients, considering GAD-7 and COVID-19 fear scores as dependent variables, showed statistically significant associations with anxiety/depression treatment hypothesis (p=0.0010 and p=0.0137, respectively). Table 3 Characteristics of the study population Table 4 Multivariate analysis performed on 28 patients who missed scheduled appointments considering GAD-7 score as dependent variable Table 5 Multivariate analysis performed on 28 patients who missed scheduled appointments considering the COVID-19 fear score as the dependent variable
Discussion
Patients with SSc represent a high-risk population for complications related to COVID-19 due to the presence of frailty and the use of immunosuppressive drugs,20,21 where a higher prevalence of SARS-CoV-2 infection associated with lung involvement occurred.22 The presence of interstitial lung disease and ongoing immunosuppressive therapy may put SSc patients at risk of developing more severe disease and higher mortality when infected with SARS-CoV-2.23,24 Since the beginning of the pandemic, the need to balance patient safety with the necessity for frequent medical checks became evident, as well as a growing interest in the psychological fragility of patients with SS.25 In Italy, during the evolution of the pandemic, additional waves of the epidemic appeared, necessitating the re-introduction of stricter restrictive measures. It is worth noting that the psychological consequences showed a correlation with the duration of the isolation time.26 Our study shows that anxiety disorder and fear related to the COVID outbreak are greater in patients with SS who have not attended scheduled appointments and are associated with lack of work activity and ongoing treatment for anxiety/depression. Our results are consistent with the scleroderma patient-centered multicenter COVID-19 cohort study, in which SSc patients showed an increase in anxiety symptoms compared to the pre-COVID-19 era, without a significant increase in depressive symptoms, and with the adequacy of financial resources associated with a better outcome.11 Similar results emerged from the Progressive Systemic Sclerosis Registry of India, where pandemic fear was the cause of outpatient visits and work loss was found to be associated with a self-reported worsening of the disease. 14 Another work from the SPIN COVID-19 cohort showed that variables associated with fear of COVID-19 were respiratory problems interfering with daily activities, insufficient financial resources, and high levels of previous stress.13 Our study identifies for the first time higher rates of COVID-19-related symptoms of fear and generalized anxiety disorder in the subgroup of patients with SSc who missed regular visits, as evidenced by validated questionnaires. These patients deserve attention regarding the presence of risk factors for missed periodic examinations, whose regularity should be ensured as suggested by the World Scleroderma Foundation.27 As found in the Taiwanese population, high anxiety and worry about COVID-19 led to non-attendance at the scheduled appointment. 28…
