Perceived stress links income loss and urticaria activity during the COVID-19 pandemic

Abstract

The pandemic of coronavirus disease 2019 (COVID-19) has caused substantially adverse effects on health and economy at both individual and societal levels. It was estimated that the worldwide unemployment rate might increase from 4.9% to 5.6% owing to the pandemic. 1 Decades of research have accumulated evidence on the adverse impacts of unemployment on poverty-related health outcomes and mental illness such as stress and anxiety. 2 Interestingly, it has been well established that allergic diseases are associated with higher socioeconomic status (SES). 3 However, it is less known whether adverse life events such as loss of income would trigger or enhance the activity of allergies. Few epidemiologic studies have addressed this question, but a recent review summarized the neuro-immuno-cutaneous crosstalk as a mechanism that links psychological stress and urticaria. 4 The outbreak of COVID-19 uniquely creates a quasi experiment and provides an opportunity to study this association. We assumed that the income loss could increase urticaria activity through mental stress, and conducted a social media-based investigation in adult Chinese patients between 27 Feb 2020 and 11 Mar 2020. A link was distributed to two WeChat groups consisting of 980 patients who were diagnosed as urticaria in the Department of Dermatology, Xiangya Hospital. Loss of income was inquired by a question “Since the epidemic of COVID-19, is there any change in your monthly income?” and was categorized as complete loss, reduced, and unaffected. The primary outcome was the activity of chronic urticaria, determined by the Urticaria Activity Score (UAS). The severities and frequencies of wheals and itch during the past 7 days were analyzed separately, and moderate-to-intense wheal/itch or frequencies of wheal/itch >1 d/week were defined as the outcomes (binary). The secondary outcomes included perceived stress (visual analogue scale, VAS), symptoms of anxiety (2-item Generalized Anxiety Disorder, GAD-2) and depression (Patient Health Questionnaire-2, PHQ-2). The cut-offs were 7, 3, and 3 for stress VAS, GAD-2, and PHQ-2, respectively. 5 , 6 Covariates for adjustments included sex, age, education, income, history of disease, and outdoor activity restriction during the pandemic. Multivariable logistic regression was used to estimate the associations with adjustments. The effect size was presented as adjusted odds ratio (aOR) and 95% confidence interval (CI). The mediation effect of stress was tested and estimated using the bootstrapping method. A P<0.05 was considered statistically significant. The data were analyzed with R version 3.5.2. A total of 234 valid questionnaires were collected, and 182 of them were adult patients with chronic urticaria. The mean age of the patients was 33.7±10.9, and 55.5% were women. Only 68 (37.3%) reported unaffected income, while 54 (29.7%) reported reduced income and 60 (33.0%) reported complete loss of income. By comparing participants’ characteristics, income loss was significantly associated with sex, educational level, income, and outdoor activity, which were further adjusted in multivariable models. In general, loss of income was dose-dependently associated with urticaria activity with respect to the severities and frequencies of wheals and itch (Table 1 ). However, after adjustments for covariates, significant associations were only observed in the frequency of wheals (aOR=2.45 for reduced income and aOR=2.13 for loss of income) and intensity of itch (aOR=2.19 for loss of income). Unexpectedly, income loss was not significantly correlated with the UAS sum score. Table 1 Association of income loss with urticaria activity and patient-reported outcomes Unaffected Reduced Complete loss Characteristics n (%) aOR n (%) aOR (95% CI) ∗ P n (%) aOR (95% CI) ∗ P Primary outcomes Frequent wheals (>1 d/week) 23 (33.8) Reference 29 (53.7) 2.45 (1.15–5.25) 0.020 32 (53.3) 2.13 (1.01–4.50) 0.048 Frequent itch (>1 d/week) 30 (44.1) Reference 29 (53.7) 1.52 (0.72–3.22) 0.271 35 (58.3) 1.90 (0.90–4.03) 0.093 Moderate-to- intense wheals 8 (11.8) Reference 9 (16.7) 1.67 (0.59–4.78) 0.338 16 (26.7) 2.61 (0.97–6.99) 0.057 Moderate-to- intense itch 20 (29.4) Reference 22 (40.7) 1.57 (0.73–3.38) 0.248 29 (48.3) 2.19 (1.02–4.68) 0.044 Secondary outcomes Anxiety (GAD-2 ≥3) 17 (25.0) Reference 18 (33.3) 1.80 (0.79–4.11) 0.161 21 (35.0) 1.34 (0.60–3.00) 0.483 Depression (PHQ-2 ≥3) 31 (45.6) Reference 26 (48.2) 1.18 (0.57–2.47) 0.657 26 (43.3) 0.83 (0.40–1.76) 0.633 Perceived stress (VAS ≥7) 3 (4.4) Reference 6 (11.1) 2.56 (0.59–11.2) 0.208 12 (20.0) 4.56 (1.17–17.8) 0.029 aOR, adjusted odds ratio; CI, confidence interval; GAD-2, Generalized Anxiety Disorder-2; PHQ-2, Patient Health Questionnaire-2; VAS, visual analogue scale. ∗ Adjusted for sex, annual income, and outdoor activity restriction. Income loss was not significantly correlated with anxiety in the multivariable model, although a higher proportion of anxiety could be observed in patients who reported income loss. Income loss was associated with perceived stress with the largest effect size (aOR=4.56, P=0.029). According to the bootstrapping estimates for mediation effect, perceived stress significantly contributed to 19.3% of the total effect of income loss on urticaria activity (P=0.040). The estimate for indirect effect was 0.03 (95%CI: 0.01–0.06, P=0.04). More importantly, income loss was no longer significantly correlated with urticaria activity after modeling stress (P=0.080). Our study examined the association of income loss with urticaria activity, in terms of the frequency of wheals and the intensity of itch, and this association is partly mediated or modified by perceived stress. The study has implications for the management of patients with chronic urticaria and further study on the neuro-immuno-cutaneous interactions. The study also has limitations, including selection bias owing to the non-probability sampling method, limited generalizability to non-Chinese and non-urticaria population, lack of longitudinal observations, incapability to infer a causal relationship owing to the observational study design, and recall bias related to the self-reported measurements. Nevertheless, to our knowledge, this is the first study that established an association of the pandemic-related impacts with adverse outcomes of chronic urticaria, and proposed a hypothesis for the black box of association. Chronic urticaria has detrimental effects on quality of life and mental health, while psychiatric comorbidities could aggravate urticaria activity in turn, resulting in a vicious circle. More importantly, the needs for disease control remain largely unmet in chronic urticaria, as a substantial number of patients benefit little from H1-antihistamines. 7 Consequently, research for novel mechanisms that involve in the neuroimmune inflammation in urticaria are needed, as it will enlighten the development of new therapeutic strategies for patients with unsatisfied disease control and impaired quality of life. Admittedly, we realized that social stressor was not urticaria’s Achilles' heel, as it only contributed to approximately 20% of the total effect. In addition, we observed no significant correlation between income loss and UAS total score, partly because of the lack of associations of income loss with the frequency of itch as well as the severity of wheals. This might introduce additional measurement errors and conceal the true effect towards null. Another possible explanation is the effect modification by SES. A study found that lower SES was associated with a larger increase in perceived stress and higher levels of interleukin-6 in survivors who experienced a disaster, indicating that individuals from different SES backgrounds respond differently to stressors both psychosocially and biologically. 8 In summary, during this pandemic period, dermatologists and psychologists can work together and remotely, to identify patients who experienced loss of income and social distancing, and to provide personalized care to minimize the adverse outcomes of urticaria and many other allergic diseases.