During the first 2 years after the initial identification of the coronavirus disease-2019 (COVID-19), the severe acute respiratory syndrome coronavirus 2 spread rapidly across the globe. Although primary emphasis is typically placed on the physical health consequences of an outbreak of an infectious disease, incidents of mental health disorders including depression, anxiety, and post-traumatic stress disorder also increase during global health emergencies [1]. A systematic review revealed a concerning prevalence of stress (29.6%), anxiety (31.9%), and depression (33.7%) in the community amid the COVID-19 pandemic [2].

Specifically, healthcare workers have been highly impacted by the COVID-19 pandemic during which they dedicated extended hours on the frontlines of the pandemic, diagnosing and providing care to patients who were infected or at high risk of being infected while consistently facing the pain and suffering experienced by their patients. They also had to sustain abnormally intense and demanding work schedules [3], and many reported work-related stress specific to the pandemic, such as concerns about contracting and spreading the virus [4]. Furthermore, they experienced reluctance to engage in work, a sense of being stigmatized, coping by avoiding crowds and colleagues, and feelings of being under scrutiny [5]. This unparalleled situation led to serious psychological issues, including depression, anxiety, and insomnia [6]. In a systematic review addressing the psychiatric problems faced by healthcare professionals (such as doctors, nurses, and allied health workers) amid the COVID-19 pandemic, it was found that the estimated rates of depression, anxiety, and post-traumatic stress disorder among these workers surpassed those observed in the general population [4]. However, when a non-specific rating scale for work-related stress is applied, an individual’s work-related stress specific to a viral epidemic cannot be measured. Thus, we developed a rating scale that can measure the work-related stress experienced by healthcare workers in response to a viral epidemic, namely the Stress and Anxiety to Viral Epidemics-3 items (SAVE-3) [7].

Among the various psychiatric consequences experienced because of COVID-19-related work stress, depression deserves critical attention because suicidal ideation and attempts are some of its symptoms. However, given that not all healthcare workers develop depression after experiencing work-related stress in response to a viral epidemic, there may be mediating factors that connect these two conditions. According to the interpersonal theory of suicide (ITS) [8], the desire for suicide is influenced by interpersonal factors, such as perceived burdensomeness (perception or feeling of not belonging or not being connected to others in a meaningful way) and thwarted belongingness (the belief that one is a burden to others and that their existence and actions impose a heavy burden on friends, family, or society). Although the theory was originally developed to explain the contributing factors for suicidal desire, previous studies revealed that the experience of thwarted belongingness and perceived burdensomeness is associated with both past and future depression [9,10]. A study on the relationship between minority stress and depressive symptoms revealed that the former was indirectly associated with the latter via perceived burdensomeness [11]. However, interpersonal factors were not studied in the context of work-related stress in response to a viral pandemic.

In contrast, resilience can be considered a protective factor against depression. Resilience pertains to an individual’s capacity to effectively cope with or adapt to stressful circumstances [12]. This encompasses multiple aspects such as personality, interpersonal connections, and temporal attributes of the stressor [13]. It also involves the capacity to perceive stress as an opportunity, acknowledge personal limits in controlling stress reactions [14], enhance self-efficacy, bolster resistance to stress, adapt, and cultivate a sense of humor [15]. Employing resilience as an adaptive coping strategy could be advantageous in diminishing work-related stress in response to a pandemic and psychiatric symptoms, including depression, among healthcare workers. A study revealed that the association between COVID-19-related work stress and depressive and anxiety symptoms of primary healthcare workers is influenced by resilience [16].

We aim to explore whether the work-related stress experienced by healthcare workers in response to the viral epidemic may be associated with depressive symptoms. Furthermore, we tried to investigate whether insomnia symptoms, interpersonal factors, or resilience influence depressive symptoms. We posited that 1) work-related stress may be positively associated with depressive symptoms, 2) insomnia may be positively associated with depressive symptoms, 3) interpersonal factors may be positively associated with depressive symptoms, 4) resilience may be negatively associated with depressive symptoms, and 5) insomnia, resilience, and interpersonal factors may mediate the association between the work-related stress and depressive symptoms experienced by healthcare workers.

Of the 329 healthcare workers, the mean age was 35.8±14.3 years old, with a mean employment duration of 9.7±7.7 years. Among them, 194 (59.0%) were nursing professionals, 267 (81.2%) were female, and 157 (47.7%) were single (Table 1). Regarding COVID-19-related questions, 45 (13.7%) responded that they experienced being quarantined, 2 (0.6%) experienced being infected, and 327 (99.4%) were vaccinated.

Healthcare workers’ depressive symptoms (PHQ-9) was significantly correlated with SAVE-3 (r=0.31, p<0.01), ISI (r=0.56, p<0.01), INQ-TB (r=0.49, p<0.01), INQ-PB (r=0.47, p<0.01), and CD-RISC2 (r=-0.39, p<0.01) (Table 2). Their work-related stress in response to the viral epidemic (SAVE-3) was significantly correlated with ISI (r=0.26, p<0.01), INQ-TB (r=0.17, p<0.01), INQ-PB (r=0.24, p<0.01), and CD-RISC2 (r=-0.17, p<0.01).

Linear regression analysis revealed that high SAVE-3 (β=0.11, p=0.012), high ISI (β=0.39, p<0.001), high INQ-TP (β=0.24, p<0.001), high INQ-PB (β=0.20, p<0.001), and low CD-RISC2 (β=-0.12, p<0.001) (F=53.03, p<0.001) (Table 3) were significantly associated with healthcare workers’ depressive symptoms during the pandemic.

Mediation analysis revealed that work-related stress in relation to the viral epidemic directly influenced the depressive symptoms of healthcare workers. Their insomnia, thwarted belongingness, and perceived burdensomeness positively mediated the association between work-related stress and depressive symptoms, and their resilience negatively mediated the association between work-related stress and depressive symptoms (Table 4 and Figure 1).

We observed that the work-related stress of healthcare workers in response to a viral epidemic was directly associated with their depressive symptoms during the COVID-19 pandemic era. Their insomnia symptoms were significantly associated with depressive symptoms and work-related stress, and resilience was negatively associated with these factors. Their thwarted belongingness and perceived burdensomeness were also positively associated with depressive symptoms and work-related stress. Furthermore, healthcare workers’ insomnia, resilience, and interpersonal factors mediated the association between work-related stress and depressive symptoms.

In this association between work-related stress and depressive symptoms, their thinking on thwarted belongingness and perceived burdensomeness had a mediation effect. According to ITS [8], thwarted belongingness and perceived burdensomeness are important factors in the development of suicidal thoughts and behaviors. Thwarted belongingness can arise when individuals experience a sense of social isolation, loneliness, or lack of connection with others, and perceived burdensomeness can arise when an individual feels that they are unable to contribute positively to the lives of others [8]. When the “need to belong” [29] is unmet, this condition is termed as thwarted belongingness and represents an interpersonal need significantly linked to suicidal ideation [8], which is a core symptom of major depressive disorder [30]. During the COVID-19 pandemic, healthcare workers felt isolated and alone because of the physical distancing policy enacted in hospitals to prevent viral infection and transmission from healthcare workers to patients [31]. In addition, they sometimes felt useless when they were unable to help or treat patients with COVID-19 [32]. We could speculate that these feelings may have caused the depression of healthcare workers during the pandemic. As work-related stress increases in relation to viral epidemics, this burden may enhance their feelings of depression mediated by thwarted belongingness and perceived burdensomeness.

Insomnia also mediated the association between work-related stress and depressive symptoms of healthcare workers during the COVID-19 pandemic. Numerous studies reported that work-related stress was associated with insomnia or depression during the COVID-19 pandemic among healthcare workers [7]. Among workers involved in cold chain management who were exposed to extreme temperatures or hazardous materials, insomnia mediated the association between their burnout and depression [7]. Chronic exposure to work-related stressors can disrupt sleep patterns via physiological responses, such as elevated cortisol levels [33], and contribute to cognitive and emotional factors, including persistent worry and anxiety [16]. The resulting insomnia may exacerbate symptoms of depression by impairing emotional regulation and reducing an individual’s ability to cope with stress [34,35].

Our observations also suggest that people with higher levels of resilience may be less susceptible to depression resulting from work-related stress. This finding is in agreement with that of a previous study on the psychological impact of COVID-19 on nurses, which showed that resilience partially mitigated the effect of perceived stress on depression [36]. This supports the conclusion that resilience had a protective effect on the emotional well-being of nurses during the pandemic. Resilience, which is defined as the ability to adapt and recover from adversity [12], appears to serve as a protective factor in this context. Those with greater resilience may be better equipped to cope with the challenges posed by work-related stressors and may exhibit reduced vulnerability to the development or exacerbation of depressive symptoms [16]. This finding underscores the importance of fostering resilience as a potential intervention strategy to buffer against the negative mental health consequences of workplace stress. A meta-analysis examined the effectiveness of resilience-building programs in the workplace and found that one-on-one formats, such as coaching, are the most effective [37]. These are followed by group formats delivered in a classroom setting.

This study has some limitations. First, this study was conducted within a single hospital; therefore, the results cannot be generalized to other hospitals or medical centers with similar settings. Second, it was conducted via an online survey, and we were unable to confirm whether the participants provided answers. Moreover, limited access to the system and self-selection bias may have led to a non-representative sample. Third, there may be a selection bias stemming from the predominance of female participants in the sample, which could limit the generalizability of the findings to the broader population, particularly to male participants. Fourth, because of its cross-sectional design, a causal relationship could not be established. Finally, some of the rating scales within this sample showed a relatively low level of reliability in terms of internal consistency.

In conclusion, this study highlights a clear connection between the heightened work-related stress experienced by healthcare workers amid the COVID-19 pandemic and the subsequent onset of depressive symptoms. Insomnia serves as a mediator in this relationship, thus emphasizing its role in exacerbating the effect of stress on mental health. Additionally, the study introduces the mediating influence of thwarted belongingness and perceived burdensomeness. Factors such as enforced physical distancing and the emotional weight of being unable to save infected patients contribute significantly to feelings of isolation and a sense of being a burden, thus potentially leading to depression. Notably, resilience emerges as a protective factor, thus indicating that individuals with higher resilience levels are less susceptible to the depressive effects of work-related stress. This study suggests that interventions that focus on building resilience could be pivotal in mitigating the detrimental mental health consequences of workplace stress among healthcare workers in the context of a viral epidemic.