Abstract

Introduction

In December 2019, a new coronavirus, which causes respiratory infection in humans (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), was reported in Wuhan, China [1]. The virus was spread worldwide, leading to the coronavirus disease 2019 (COVID-19). On March 11, 2020, the World Health Organization (WHO) declared COVID-19 a global pandemic, and until July 2022, over 547 million confirmed cases and over 6 million deaths have been reported worldwide [2, 3]. Due to the initial absence of vaccines and specific treatment, measures such as use of masks, social distancing, quarantine, and isolation were imposed to prevent virus transmission [4]. As a consequence, this public health issue had a serious impact on several daily life aspects.

Sleep is a vital physiological process, associated with essential functions, required for maintaining physical and mental health [5, 6]. Sleep plays an important role in homeostasis, immune system, cognitive function, neural plasticity, memory, energy maintenance, macromolecular biosynthesis, and metabolism regulation [7, 8], while sleep deprivation leads to impaired physical and mental performance and has been associated with obesity, diabetes, hypertension, and cardiovascular disease [9].

Previous studies have shown that COVID-19 has a negative impact on public mental health, as it is linked to fear, anxiety, depression, and sleep disorders [10•]. Sleep was affected by several factors during the pandemic such as isolation, stress, fear of infection, reduced physical activity, and exposure to daylight [5]. Moreover, sleep dysfunction was prevalent not only in the general population, but also in infected patients and healthcare workers [6]. The aim of this review is to make an overview about the link between sleep deprivation, immune system, and COVID-19 severity, to present the prevalence of sleep disorders in different populations during the pandemic (i.e., patients with COVID-19, healthcare professionals, and general population) and to summarize the risk factors and the management options to alleviate sleep disorders in these populations.

Sleep Disorders in COVID-19 Patients

Prevalence

Numerous studies were conducted during the pandemic, focusing on sleep disorders in COVID-19 patients. The prevalence of sleep disorders was found to range between 34 and 82% [6, 10•, 11, 12••, 13–16]. In a recent systematic review with meta-analysis, which included 250 studies from 49 countries, patients with COVID-19 were the most affected, with a pooled estimated prevalence of sleep problems at 52.39% [12••]. In another meta-analysis, which included studies solely from China, the prevalence of insomnia in COVID-19 patients was 48.7% [11]. It was also exhibited that patients with COVID-19 or other chronic medical problems had higher risk to develop insomnia [11]. In a large-scale meta-analysis, Dragioti et al. demonstrated that disturbed sleep was one of the most frequent mental health issues in COVID-19 patients, with a prevalence of 63% [13]. On the other hand, another meta-analysis reported lower prevalence of sleep disturbances, with only 34% of patients with SARS-CoV-2 exhibiting sleep disorders [15]. Concerning symptom severity, it was mild in 20%, moderate in 16%, and severe in only 2% [15]. As of gender, Alimoradi et al. found that the prevalence of sleep problems was 39% in male and 51% in female patients [14]. It was assumed that this difference could be attributed to the different brain structures and functions among sexes, as it was demonstrated in previous studies [14]. The highest prevalence of sleep disturbance in COVID-19 patients was reported in the meta-analysis of Krishnamoorthy et al., who found poor sleep quality in the 82% of these patients [10•]. An overview of available meta-analyses, referring to sleep disorders in COVID-19 patients, is presented in Table ​Table11.

Table 1

Prevalence of sleep disorders in COVID-19 patients across meta-analysis

Study	Sample	Assessment tools	Pooled prevalence	Limitations
Li et al. [11]	6 studies, 1780 patients	• ISI • PSQI • ASI • SRSS	48.7% (95% CI 21.6–75.8%, I2=99.5%)	• High heterogeneity • Studies only from China
Jahrami et al. [12••]	16 studies, 6821 patients	• ISI • PSQI • ASI • Research developed	52.39% [41.69; 62.88%], I2=98.10%	• High heterogeneity
Dragioti et al. [13]	15 studies	• ISI	63% [95% CI 23–94%]	• Focusing on general mental health impact • Heterogeneity not applicable
Alimoradi et al. [14]	7 studies	• ISI • PSQI	Males: 39% [95% CI 27–50%, I2=97.58%] Females: 51% [95% CI 42–60%, I2=99.43%]	• High heterogeneity
Jahrami et al. [6]	3 studies, 1884 patients	• ISI • PSQI • ASI • Research developed	74.8% [95% CI, 28.7–95.6%, I2=96%]	• High heterogeneity • Sleep disorders not the primary focus in some studies
Deng et al. [15]	10 studies, 1795 patients	• ISI • PSQI • Research developed • Clinical interview	34% [95% CI: 19–50%, I2=98%]	•High heterogeneity • Most studies from China
Alimoradi et al. [16]	10 studies	• ISI • PSQI • Others not referred	57% [95% CI: 42–72%, I2=98.5]	• High heterogeneity • Most studies cross-sectional

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ISI Insomnia Severity Index, PSQI Pittsburgh Sleep Quality Index (PSQI), ASI Athens Insomnia Scale, SRSS Self-Rating Scale of Sleep

Pathophysiology and Risk Factors

The new coronavirus leads to sleep disruption either directly, by infecting the central nervous system (CNS), or indirectly, through COVID-19 provoked cytokine storm [5]. More specifically, coronavirus can enter CNS through nasal mucosa and olfactory pathway or through blood–brain barrier, by infecting the endothelium and the leucocytes [17]. By using ACE-2 receptors, the virus can invade in cerebral structures, including brainstem and hypothalamus, resulting in dysregulation of sleep–wake cycle [17, 18]. In addition, COVID-19 triggers extensive inflammatory response and cytokine storm, that increases blood–brain barrier accessibility and induces immunologic tissue insult, neuropsychiatric symptoms, and sleep disorders [5, 17].

Other factors resulting in sleep disorders in COVID-19 patients are related to symptoms and psychological impact caused by the infection, as well as to social changes provoked by the pandemic. COVID-19 patients experience intense stress related to uncertainty on the course of the illness, fear of adverse outcome, and isolation from loved ones [5, 10•]. In addition, they have to be confined in isolation wards or in their home, facing, sometimes, discrimination, and social stigma [5, 10•]. Anxiety and depression, due to the above circumstances, are strongly associated with sleep disturbance [5]. The core symptoms of COVID-19, i.e., cough, fever, pain, and dyspnea, have, also, negative impact on sleep quality [11]. Moreover, hospitalization could further impair sleep quality due to noise, exposure to lights, alerted sleep routine, clinical interventions, and medication’s side effects [12••, 19]. A summary of the factors relating to sleep disorders in COVID-19 patients are presented in Fig. 1.

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Fig. 1

Factors resulting to sleep disorders in patients with COVID-19

Sleep Disorders in Healthcare Professionals During COVID-19 Pandemic

Based on previous experience from SARS and Ebola epidemics, an unexpected and life-threatening disease could provoke excessive pressure and stress in healthcare workers (HCWs) [53]. Due to the nature of their work, HCWs were placed in the center of the pandemic, confronted with the effects of the virus and managed heavy workloads; thus, their physical and mental well-being was negatively affected [54•]. Existing evidence suggests that the prevalence of psychological morbidity in HCWs during COVID-19 pandemic is higher than that of previous epidemics [55].

Several studies investigated the effect of COVID-19 pandemic in sleep quality of HCWs. The prevalence of sleep disorders ranged between 23.1 and 64.3% [56••]. In a recent umbrella review of 26 meta-analyses, the prevalence of sleep disorders in hospital staff during the pandemic was 39.45% [56••]. The authors also demonstrated that nurses suffered more from sleep problems/insomnia compared to doctors, probably because of different responsibilities, tasks, and working hours [56••]. On the other hand, Salari et al., in their meta-analysis, found that sleep disorders are greater in physicians compared to nurses [57]. Numerous studies suggested that, irrespective of their profession, frontline HCWs were more prone to develop sleep disorders due to close contact with patients, anxiety, fear, and exhaustion [56••, 58–60].

Assorted causes are implicated in the development of sleep disorders in HCWs. First of all, HCWs are subjected to heavy workload, unusual work schedules, and more night shifts because of the increased requirements in hospitals during the pandemic [61]. Moreover, they have to change their lifestyle routine and minimize daytime activity [54•]. As a consequence, these alterations may dysregulate circadian rhythm leading to sleep disorders [22]. Furthermore, they frequently face changes in hospital role and work team, factors that may cause uncertainty and anxiety [54•]. In addition, HCWs in COVID-19 wards and ICUs are exposed to stress factors such as patients’ fears and expectations, high fatality rates, shortages of personal protective equipment, and fear of being infected [54•, 62]. Moreover, they are isolated from their loved ones as they worry not to spread the virus [62]. Stress, provoked by those factors, may disrupt hypothalamic-pituitary adrenal axis and autonomic nervous system and, thus, result in sleep disturbance [63].

Sleep deprivation in HCWs not only affects negatively their work performance but also their well-being. Lack of sleep has been associated with work-related errors and lower quality of care [62, 64]. Additionally, shift workers are more susceptible in developing both mental and physical diseases. More specifically, insufficient sleep has been related with higher risk of cardiovascular disease, obesity, stroke, gastrointestinal disorders, anxiety, loss of interest, and depression [64]. Concerning COVID-19, shift workers are more vulnerable to respiratory infections, including SARS-CoV-2, and probably to more severe course of disease [65].

Therefore, it is crucial to adopt appropriate interventions to confront sleep problems among HCWs in order to prevent physical and mental disorders and improve their resilience. Supportive measures include the development of a suitable work environment by reducing shifts, hiring new staff, providing adequate protective personal equipment, and improving team cohesion [54•, 63]. HCWs should have access to mental health professionals and be encouraged to express their feelings and their fears [63]. Other practical recommendations encompass relaxing by reading, exercising, taking naps, setting a sleep-friendly environment, and following a regular sleep routine when it is feasible [54•, 64].

Sleep Disorders in General Population During COVID-19 Pandemic

Apart from COVID-19 patients and HCWs, the pandemic has also affected the general population. COVID-19-related sleep dysfunction has been established in many scientific papers. In a recent global meta-analysis, the prevalence of sleep disorders in general population was 36.73% [12••]. Similar results were also published in previous meta-analyses [10•, 13, 16]. However, other studies found lower prevalence of sleep disorders, ranging between 26 and 29% [11, 14•, 66]. The heterogeneity in the results could be explained by the different tools which were used to assess sleep across the studies, as the majority of them used self-reported data. Conflicting results have been reported when comparing sleep habits before and during the pandemic. More specifically, some studies demonstrated that sleep duration remained constant, while others reported increased sleep time due to changes in daily and working routine [67–70]. The flexibility in work time and the work-from-home may provide the opportunity for longer sleep duration. However, negative emotions and stress may affect other sleep characteristics (i.e., awakenings during the night and frequent nightmares) impairing the overall sleep quality [67]. Wang et al., found an increase in sleep duration (with delayed bed and wake times) and a decrease in sleep quality during the pandemic, by using wrist actigraphy and self-reported data [71].

As far as other sleep characteristics, Vladutu et al. demonstrated that, among 328 university students, the prevalence of sleep bruxism was 16.28%, and it was significantly associated with COVID-related stress, while Winocur-Arias et al. found that sleep bruxism was more prevalent exclusively in women during the pandemic [72, 73]. In addition to that, oneiric activity was also modified during the pandemic. Higher frequency of nightmares and increased dream recall were observed, a fact that was related with parasomnia [74, 75]. Dream content also changed, becoming more negative (i.e., dreaming about diseases, war, and death) [74]. Gorgoni et al. reported that dream frequency, vividness, bizarreness, lucid dreams, and emotional load reduced after lockdown [76].

Circadian misalignment, developed during the pandemic, could explain the aforementioned sleep disturbances. Lockdown and atypical work/school schedules resulted in reduced sunlight exposure and daily physical activity [52••, 77]. Additionally, increased screen time (i.e., increased use of smartphones and social media) has been shown to impair the secretion of melatonin [77]. The flexibility of work/school schedule could allow individuals to sleep more in synchrony with their circadian tendency, promoting greater circadian alignment. However, as mentioned above, literature suggests the opposite. This could be explained by the fact that many people with fixed daily schedule before the pandemic developed a stable sleep schedule and sleep habits, something that promoted circadian alignment. On the other hand, the greater flexibility during the pandemic disrupted their sleep schedule, promoting circadian misalignment. Therefore, their circadian rhythm might have been disrupted, leading to sleep disorders [52••, 77]. Furthermore, people were extensively exposed to stressful situations during the pandemic. Fear of being infected, lack of knowledge about the disease, misinformation, and rumors generated increased worry and stress [10•]. Moreover, isolation and separation from loved ones, restrictions, and uncertainty about employment and financial state resulted in excessive anxiety [10•]. These factors reflect the psychological sphere and might deteriorate sleep quality.

The optimal strategy for treating COVID-related sleep disorders remains unclear. CBT is the gold standard in the case of insomnia, and during a lockdown, it could be implemented via telemedicine [44]. Furthermore, it seems essential to adopt sleep hygiene practices. Following a regular sleep program, exercising enough, subjecting to light during daytime, minimizing screen time, and avoiding caffeine and other stimulants may improve sleep quality [77].

Conclusions

COVID-19 pandemic has increased the prevalence of sleep disorders in different populations. Sleep problems appear to be considerably common in COVID-19 patients and have been associated with more severe disease and poor clinical outcome. HCWs, subjected to heavy workload and nightshifts, also suffer from sleep disturbances, provide lower quality of care, and are more susceptible to infection and physical disorders. General population was also affected in terms of sleep quality, being exposed to many stressors. Effective interventions and measures should be implemented in order to improve sleep quality and reduce the mental and physical consequences from its disturbance. Further studies are needed to provide high-quality information on the effectiveness of the implemented interventions.

Declarations

Footnotes

Contributor Information

Ioanna Papagiouvanni, Email: moc.liamg@pap.d.annaoi.

Serafeim–Chrysovalantis Kotoulas, Email: moc.liamtoh@saluotoksika.

Christos Vettas, Email: moc.liamg@sattevsirhc.

Evdokia Sourla, Email: rg.oohay@uosive.

Athanasia Pataka, Email: rg.oohay@htakatap.

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