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Sleep disturbances may be seen in up to three-fourth of COVID-19 patients, and up to two-fifth of health care workers and general population.
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Older age, having a partner alongside, and staying in a high-income country reduced the risk of sleep disturbances.
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Younger age, female sex, financial problems and coexisting stress, anxiety, and depression enhanced the risk of sleep disturbances.
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Etiology of sleep disturbances in COVID-19 pandemic is multifactorial. Three major factors neuroinvasion by SARS-CoV-2, social factors and health-policy changes during the pandemic can be implicated as contributors.
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A close association of sleep with immunity and metabolism means identification and treatment of sleep disturbances are essential during the pandemic time.
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Support from “Telemedicine sleep clinic” along with motivating the population to manage the zeitgebers may improve sleep during the pandemic.
Introduction
A pandemic is described as a state where a disease evolves quickly, affects a significant proportion of the population, and usually spreads across geographic boundaries to involve more than one continent.
In the 21st century, the world has suffered 3 pandemics: severe acute respiratory syndrome (SARS-CoV) in 2003, Swine Flu (H1N1) in 2009, and since late 2019, COVID-19 (SARS-CoV-2).
Among them, the COVID-19 pandemic had the most marked effect on health through direct and indirect factors, by inducing physiologic alteration across systems and by paving way for economic as well as political changes in a time of scientific uncertainty.
Sleep is one of the important physiologic activities performed by all animal species. Contrary to prevalent belief of many, sleep is no longer considered as a period of inactivity by the sleep scientific community. Indeed, it is associated with several important functions required for a healthy life—rejuvenation, memory consolidation, modulation of immune function, and regulation of hormonal secretion.
The pandemic has affected sleep in different ways. For a considerable proportion of the population, sleep has worsened in terms of quality, duration, and timing, but for a small proportion, it has improved.
Sleep was affected by several factors during the COVID-19 pandemic. Unprecedented lockdowns limited zeitgebers (eg, physical activity, exposure to daylight, social rhythm, screen exposure, time of food intake) that regulate the sleep-wake cycle. Studies have also shown that a sizable number of people experience distress associated with uncertainties regarding the course of treatment and outcome of SARS-CoV-2 infection, as well as their employment.
Though the impact of pandemics on sleep has also been studied, it has been most extensively researched during the current COVID-19 pandemic. This article will present the available literature and will be divided into the following sections for better understanding.
1.
Magnitude of sleep disturbances during the pandemic
2.
Determinants and pathophysiology of sleep disturbances during COVID-19 pandemic
3.
Long-term perspectives of sleep disturbances
4.
Why is there a need to pay attention to sleep disorders during pandemics
5.
Management of sleep disturbances during a pandemic
Magnitude of sleep disturbances during the pandemic
Sleep disturbances during pandemics have been reported across different age groups and in a variety of populations ranging from the general population and front-line workers to hospitalized and quarantined patients with SARS-CoV-2 infection. Available studies focused on the assessment of sleep quality, sleep-wake schedule, and insomnia.
The magnitude of sleep problems reported in studies is influenced by several factors: time at which the problem was assessed (lockdown vs after unlocking), age, gender, comorbidity, and medication history of subjects. It has been reported that detrimental changes in sleep pattern during early lockdown tend to remain the same unless early intervention is provided.
Choice of questionnaires and measures used to assess sleep also affected the results across studies. For example, a higher prevalence of poor sleep quality has been reported from the studies using standardized measures of sleep like the Pittsburgh Sleep Quality Index (PSQI) compared with studies using other scales and investigator-developed measurements.
Cut-off scores of the questionnaires also influenced the outcomes; the cut-off for the PSQI was higher than standard in some of the studies that could have resulted in lower prevalence.
Psychological and behavioral impact of lockdown and quarantine measures for COVID-19 pandemic on children, adolescents and caregivers: a systematic review and meta-analysis.
Sleep health includes 6 measures, namely regularity of sleep-wake schedule, duration of sleep, timing of sleep and wake, satisfaction with sleep, sleep efficiency, and daytime alertness. These are all indirect measures of sleep quality.
There was a geographic variation in sleep health, with poorer sleep health among residents of Latin American and Caribbean countries compared with residents of North America, Europe, and Central Asia.
Owing to geographic variation, pooled analysis would provide better estimates of disturbed sleep among the general population. A systematic review reported that in the general population, nearly one-third had reported disturbed sleep.
Similar to the general population, geographic variation of sleep disturbance was also noted among HCWs; it was lower in China compared with other countries like Bahrain and Iraq.
Contrary to intuitive deduction, it is difficult to reliably comment whether prevalence has actually increased among HCW during the pandemic as it appeared comparable to pre-pandemic time at least by one at study group.
A systematic review of cross-sectional studies reported that sleep quality was poor during the pandemic, not only in HCWs (irrespective of their engagement in the management of COVID-19 patients during the pandemic) but also among nonhospitalized individuals (irrespective of the status of SARS-CoV-2 infection).
This is a situation similar to paradoxic insomnia wherein despite an adequate sleep duration, sleep is still nonrefreshing, perhaps owing to increased cortical activation.
Patients with SARS-CoV-2 infection make the largest proportion of the group in which sleep quality was poor during pandemic (nearly three-fourth reported).
This is in contrast to another meta-analysis, which reported that only 34% of patients having SARS-CoV-2 infection had disturbed sleep or poor quality sleep.
In the latter paper, most of the studies were from China, whereas the earlier paper represented better global prevalence because it included studies from various countries.
Contrary to reports of poor or worsening sleep quality in most studies, a minority of the population (6%) reported improvement of sleep during the pandemic.
With one study reporting nearly a quarter of subjects having improvement in sleep quality during the lockdown irrespective of the total sleep time at night.
Taken altogether, the available data show that geographic variation exists among subjects reporting poor sleep quality both in the general population and in patients suffering from SARS-CoV-2 infection. These factors could also emphasize the role of genetics in their vulnerability (eg, MEIS1 gene has been found to be associated with insomnia, MEIS1 and BTBD-9 have been found to increase the risk for restless legs syndrome, etc.) to develop sleep disturbances in association with environmental factors.
However, sleep quality did not take a downhill course throughout the pandemic. It seemed to worsen in the initial phase of lockdown and thereafter remained stable.
Two major shifts in the sleep-wake schedule were reported during the COVID-19 pandemic—delayed sleep phase and extension of sleep time. A shift to a later bedtime and later wake time was reported by nearly 50% to 60% of the adult population in an online survey conducted across 59 countries.
In Canada, 63% of subjects had earlier bedtime and later wake time during the lockdown, whereas only 2% of the population reported the same from India.
This suggested an extension of bedtime that had occurred during the pandemic in some of the population. Extension of sleep resulted in reduction of social jet lag during lockdowns and maintained consistent circadian rhythm across weeks.
Although difficulty in sleep initiation resulted in delayed awakening, prominent problems in sleep maintenance and early morning awakenings resulted in reduced total sleep time.
There is no meta-analysis available on sleep-wake schedule for this population. Findings across different individual studies, on the other hand, appeared to contradict one another. One study reported a change to a later bedtime and wake time on weekdays, but not on weekends (which were already delayed even before lockdown).
Interestingly, the sleep-wake changes did not develop to a free-running type of schedule. Rather, it worsened for an initial period after lockdown and remained stable thereafter.
Those who used to sleep shorter than 6 to 8 hours before pandemic had reduced sleep duration pandemic, whereas those who usually slept for 6 to 8 hours during pre-pandemic period, did not report any change in either their sleep duration or had an increase in time spent asleep.
Psychological and behavioral impact of lockdown and quarantine measures for COVID-19 pandemic on children, adolescents and caregivers: a systematic review and meta-analysis.
Being cross-sectional in design, this study was not able to comment on the change in sleep duration. There was an increase in total sleep time on weekdays, but there was no change on weekends reported after lockdown.
Based on the change in sleep-wake schedule during pandemic, 3 populations were identified in one study—extended time in bed (63% subjects), reduced time in bed (13%), and delayed sleep (24%).
Perhaps these people were able to follow their own sleep-wake schedules because of lack of compulsion to adhere to a structured routine. Gupta and colleagues
identified 3 groups in a population based survey—reduced sleep duration (16%), extended sleep duration (18%), and participants where total sleep time remained unchanged (66%). Similar to results of above mentioned study, nearly equal proportion of participants (28%) in this study fell into the “delayed sleep” category. Subjects in the reduced sleep group reported prolonged sleep onset latency and depressive features.
Thus, the available data suggest that sleep schedule vary across studies. The lower prevalence in the Gupta and colleagues study could be related to the inclusion of HCWs in the study population.
Underlying factors are not known but could be related to the availability of teleconsultation facilities, ability to spare time for health issues, and increased awareness of health issues in view of the prevailing situation.
Contrary to adults, sleep disorders increased among children. There was an increase in difficulty falling asleep, night-time awakenings, nightmares, sleep terrors, and excessive daytime sleepiness in the preadolescent age group.
Determinants and pathophysiology of sleep disturbances
Several factors were responsible for clinically significant sleep disturbances during the pandemic (Table 2). Interestingly, the presence of anxiety (threat perception) among parents lessened the sleep time of children, suggesting the role of shared genes as well as the environment in the occurrence of anxiety.
Several potential pathways of neuro-invasion have been suggested for SARS-CoV-2. It may have a trans-synaptic spread where the virus retrogradely travels to the CNS after entering the peripheral nerve terminals of its primary target organs viz., oronasal mucosa and lungs. From nasal mucosa, it may spread through cribriform plate and olfactory pathways to reach the cerebral cortex. SARS-CoV-2 can also enter CNS by crossing the blood-brain barrier (BBB) through one of the two routes-either by infecting and traveling across vascular endothelium or by infecting leukocytes, which then cross the BBB (“Trojan Horse” mechanism).
Once inside the brain, SARS-CoV-2 invades tissues with ACE-2 receptors including the frontotemporal cortex, circumventricular organs, thalamus, and brainstem involving the rostral ventrolateral medulla among others.
Involvement of the hypothalamus and the brainstem may result in impairment of sleep-wake cycle regulation and dysautonomia with cardiorespiratory dysfunction, thereby, resulting in poor sleep quality presenting as insomnia and sleep-disordered breathing.
Although the primary involved organ in SARS-CoV-2 is the lungs, other organs including the heart and kidneys may also be infected causing cardiorespiratory and metabolic derangements. The former may result in hypoxic-ischemic events and the latter causes metabolic encephalopathy.
In addition, a systemic inflammatory response may increase the BBB permeability, thereby, predisposing the brain to immunologic insult from a cytokine storm, which may precipitate neuropsychiatric features.
In addition, the possibility of pulmonary fibrosis after severe COVID pneumonia may result in OSA and sleep-related hypoventilation as a long-term post-COVID complication.
Systemic hyperinflammation leading to deranged immunity in COVID-19 may lead to BBB compromise and involvement of the gut-brain axis, thereby, raising the possibility of developing chronic neuroinflammatory and neurodegenerative disorders such as Parkinson disease, multiple sclerosis, narcolepsy, and associated sleep disorders.
During the pandemic, COVID-19 patients are confined in hospitals or quarantined in their homes/facilities. Most of the noninfected population remain restricted in their homes. COVID-19 has been linked to increased anxiety and psychological distress in affected patients. Psychological distress may result from physical discomfort, hospitalization in an unknown scenario among unacquainted caregivers, and uncertainty in the course of illness.
Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.
Dealing with sleep problems during home confinement due to the COVID-19 outbreak: practical recommendations from a task force of the European CBT-I Academy.
This may be due to disrupted circadian rhythm owing to lack of exposure to bright light, change in sleep-wake pattern, reduced physical exercise, unpredictability regarding health and economic condition in the general population confined at home.
From the onset of this pandemic, focus of the health system shifted toward COVID-19, and rightly so. But this significantly impacted the availability of medical care for patients suffering from other medical disorders including those with prepandemic neuropsychiatric illnesses.
A significant reduction in laboratory-based continuous positive airway pressure or bilevel positive airway pressure (PAP) titration studies was reported.
These changes in health policies could have resulted in increased anxiety and psychological distress and contributed to further worsening of sleep in patients with pre-existing pre sleep disorders.
Increased anxiety and psychological distress activate the hypothalamus-pituitary-adrenal axis and stimulate cortisol secretion. Sleep disruption resulting from increased anxiety and psychological distress may further worsen stress, forming a vicious cycle between stress and sleep disruption.
The resulting hypercortisolism dampens the proinflammatory pathways and antiviral immunity suffers. Increased norepinephrine levels in sleep-disrupted patients suppress natural killer cells, thereby, further compromising the immune status.
Reduced night-time melatonin, observed in patients with disrupted sleep, may deprive the patient of its anti-inflammatory, antioxidant, and immunomodulatory properties, thereby increasing risk of infection there.
Thus, the etiology of sleep disturbances during COVID-19 appears multifactorial. If left unattended, sleep deprivation may result in enhanced functioning of proinflammatory cytokines including interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha; and suppression of anti-inflammatory cytokines including IL-10.
Unmanaged sleep abnormalities in the general population increase the risk of COVID-19 and can negatively influence the recovery of those infected. Thus, sleep disruption during the pandemic appears to play an essential role in the propagation of COVID-19.
Effect of pandemic on patients with existing sleep disorders
There is an increase in the risk of contracting COVID-19 infection among patients with sleep disorders, especially OSA. The pandemic led to the closure of sleep medicine facilities and a sharp decline in available services, leaving patients with sleep disorders without treatment.
This could reduce the cost of care for patients, especially indirect costs incurred toward the treatment.
Long-term perspectives of sleep disorders in view of pandemic
As discussed in the pathophysiology section, SARS-CoV-2 infection may leave a permanent scar in the form of neuropsychiatric sequela. Rogers and colleagues
Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.
reported that 12% of subjects reported insomnia as long as 24 months after recovery from SARS and MERS infection. Insomnia has been reported in nearly one-third of the patients even after months of recovery from SARS-CoV-2 infection.
Literature derived from SARS infection shows that nearly a quarter of patients suffer from anxiety, depressive feelings, and post-traumatic stress disorder (PTSD) during acute infection until after 6 months.
History for some or lesson for all? A systematic review and meta-analysis on the immediate and long-term mental health impact of the 2002–2003 Severe Acute Respiratory Syndrome (SARS) outbreak.
These disorders are frequently associated with disturbed sleep, especially insomnia. Other sleep disorders, for example, restless legs syndrome, parasomnia may arise in association with psychotropics used for the treatment of these disorders. HCWs were likewise found to have anxiety, depressive features, and PTSD during and after the SARS pandemic.
History for some or lesson for all? A systematic review and meta-analysis on the immediate and long-term mental health impact of the 2002–2003 Severe Acute Respiratory Syndrome (SARS) outbreak.
Hence, there is a need to screen HCWs for sleep disturbances and sleep disorders even after the COVID-19 pandemic is over.
Why is there a need to pay attention to sleep disorders during pandemics?
Several factors emphasize the need to pay attention to sleep. First, systemic inflammatory changes and sleep disturbances run in a vicious cycle. To interrupt it, attention should be paid to reduce systemic inflammation as well as restore good quality and optimal sleep. Second, vaccination is considered a major weapon against the SARS-COV-2 infection. Sleep deprivation reduces the immune response to vaccines
and optimal duration of sleep is important for mounting an adequate immunologic response after vaccination. However, data regarding sleep quality are not available.
It is a known fact that obesity is a risk factor for OSA. Increased production of cytokines, reduced adiponectin, endothelial dysfunction, activation of prothrombotic cascade, ectopic lipid in alveolar type 2 cells, and insulin resistance have been proposed to worsen course of SARS-COV-2 infection among these individuals.
OSA has been found to worsen many of these parameters, adding the risk reported in earlier studies.
Management of sleep disturbances and sleep disorders
In response to the COVID-19 pandemic, several medical societies have proposed guidelines to improve sleep for patients, strategies to manage sleep disorders, and continue sleep-related services for patients during the lockdown. Table 3 summarizes these published guidelines.
Table 3Published literature for sleep medicine practice during the pandemic
S.N.
Title
Society
Issues Addressed
1.
Considerations for the practice of sleep medicine during COVID-19
Mitigating risk of personnel, facility, and equipment
2.
Dealing with sleep problems during home confinement due to the COVID-19 outbreak: Practical recommendations from a task force of the European CBT-I Academy
Dealing with sleep problems during home confinement due to the COVID-19 outbreak: practical recommendations from a task force of the European CBT-I Academy.
Restoring Pulmonary and Sleep Services as the COVID-19 Pandemic Lessens. From an Association of Pulmonary, Critical Care, and Sleep Division Directors and American Thoracic Society-coordinated Task Force
Restoring pulmonary and sleep services as the COVID-19 pandemic lessens. From an Association of Pulmonary, Critical Care, and Sleep Division Directors and American Thoracic Society-coordinated Task Force.
Sleep disturbances during the lockdown were multifactorial and occurred only in predisposed subjects, as already discussed. As sleep-wake schedules have changed in a large proportion of the population, it has been advised that maintenance of proper routine and sleep hygiene practices needs to be followed even during lockdown.
Timing of intervention is important. Early intervention is more useful for prevention and can be achieved through dissemination of educational information, whereas intervention initiated in the later period needs to be more structured and individualized.
There is a need to educate the population regarding the importance of adequate sleep duration and manage work schedules irrespective of prevailing situations. This will help lessen sleep deprivation and boost immunity. Time saved from commuting and reduced workload may be used to increase daylight exposure, exercise, and social communication, and cultivate hobbies. All these factors are known to improve sleep quality.
Dealing with sleep problems during home confinement due to the COVID-19 outbreak: practical recommendations from a task force of the European CBT-I Academy.
As OSA is a risk factor, at least for contracting SARS-CoV-2 infection with potentially poor outcomes, patients should be screened for OSA. The 5 items of the Sleep Symptoms Scale can be used and high-risk patients may be advised home sleep apnea testing (HSAT), attended polysomnography, mitigation strategies, or titration with PAP device as per prevailing guidelines.
Reduction of exposure to negative information, particularly related to COVID-19, scheduling time to introspect and identify stress, sharing the stress with members of the family to identify possible solutions, reduction and sharing of burden for daily chores, and engagement in relaxing activities before bedtime have been recommended to improve sleep.
Dealing with sleep problems during home confinement due to the COVID-19 outbreak: practical recommendations from a task force of the European CBT-I Academy.
Dealing with sleep problems during home confinement due to the COVID-19 outbreak: practical recommendations from a task force of the European CBT-I Academy.
Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of sleep medicine clinical practice guideline.
During the COVID-19 pandemic, sleep disturbance increased in selected groups. Owing to the closure of sleep medicine services, patients had limited access to appropriate care and telemedicine became a viable alternative. Several sleep societies developed guidelines to improve sleep health in different populations and to adapt the practice of sleep medicine during the pandemic. Sleep disturbances were also shown to have a multifactorial origin. Evidence from basic sciences and clinical literature suggests that sleep disturbances can run a chronic course, and there is a need to educate people about sleep disturbances during the pandemic. Lastly, patients suffering from SARS-CoV-2 infection should also be screened and treated for sleep disorders during the acute phase and after recovery.
Clinics care points
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All patients should be screened for sleep quality and sleep patterns during the pandemic time
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Knowledge about sleep hygiene rules should be offered to all patients
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Patients with existing sleep disorders or at high risk for sleep disorders should be referred to sleep physicians for the management of sleep disorders
Disclosure
The authors have nothing to disclose.
References
Swetha G.
Eashwar V.M.A.
Gopalakrishnan S.
Epidemics and pandemics in India throughout history: a review article.
Psychological and behavioral impact of lockdown and quarantine measures for COVID-19 pandemic on children, adolescents and caregivers: a systematic review and meta-analysis.
Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.
Dealing with sleep problems during home confinement due to the COVID-19 outbreak: practical recommendations from a task force of the European CBT-I Academy.
History for some or lesson for all? A systematic review and meta-analysis on the immediate and long-term mental health impact of the 2002–2003 Severe Acute Respiratory Syndrome (SARS) outbreak.
Restoring pulmonary and sleep services as the COVID-19 pandemic lessens. From an Association of Pulmonary, Critical Care, and Sleep Division Directors and American Thoracic Society-coordinated Task Force.
Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of sleep medicine clinical practice guideline.