**13. Discussion**

Sleep doubles as an important component of activity cycle and a restorationdriven physiological state [107, 109, 127]. Inability to sleep or insufficiency of sleep in frontline health workers managing COVID patients is caused by and has been associated with a number of adverse consequences [83]. Anxiety either due to fear of infection or an increase in job demand, hypertension, chronobiological disruption, prolonged exposure to artificial light, and stress are important contributing factors to insomnia experienced by frontline COVID-19 health workers. Sleep disruption

#### **Figure 2.**

*Prolonged light exposure and sleep disorders in frontline health workers during COVID-19. Pineal melatonin becomes suppressed by prolonged exposure to light resulting into disruption of normal circadian sleep.*

in frontline health workers may present a number of ugly consequences including neurocognitive decline. This is due to a number of reasons. The dura mater appears to be involved in the clearance of brain toxins via a novel lymphatic system of neuroglia referred to as the "glymphatic" clearance system. Glymphatic clearance is shown to occur mainly during slow-wave sleep [67]. During slow-wave sleep, brain levels of adenosine, the main metabolite of ATP, and TNF-alpha, a primary pro-inflammatory mediator of immunity, appear to increase; whereas the brain's acetylcholine and monoamines (norepinephrine, dopamine, and serotonin) decrease. Disruption of slow wave sleep experienced by frontline COVID-19 health workers makes it difficult to eliminate brain toxins and increases the risk of diseases including sleep disorders.

Anxiety in frontline COVID-19 health workers is another concern. Generally, anxiety is characterized by sympathetic activation. Increased expression of Cannabinoid type-1 (CB1) receptors owing to activation of the sympathetic nervous system has been documented [87]. CB1 receptors are expressed in the brain where they modulate GABA release culminating in sleep deprivation. Moreover, decline in basal forebrain brain derived neurotrophic factor (BDNF) and adenosine and a rise in nitric oxide in animal models have been linked with emotional disorder-related alteration in sleep pattern [89]. Hippocampus, a birthplace of theta waves, plays an important role during sleep. Depletion of hippocampal glycogen and attendant alteration in EEG waves may atone for sleep disruption that characterizes COVID-19 frontline health workers [92]. CRH is released during stress and anxiety and this hormone has been shown to depress NREM waves in C57BL/67 and CRH-R1 CL mice [97]. Spontaneous reticular thalamic discharges, implicated in synchronizing NREM waves, are known to suppress cortical activation by peripheral stimuli. Disruption of sleep occasioned by Inhibition of spontaneous reticular thalamic discharge has been reported following CRH injection [94].

Spontaneous discharge of noradrenergic fibers during basal state may explain how hypertension causes insomnia in frontline COVID-19 healthcare workers [104]. Disruption of normal secretory rhythm of hormones and chemical messengers and presence of circadian genes such as CLOCK rs1801260 locus bearing TC and CLOCK *Occupational Stress-Related Sleep Anomaly in Frontline COVID-19 Health Workers… DOI: http://dx.doi.org/10.5772/intechopen.109148*

rs680524 bearing GC and CC may contribute in substantive level to sleep disruption in frontline COVID-19 health workers. At least, studies have indicated an alteration in the circadian rhythm of leptin in people with sleep deprivation [113]. Changes in the normal secretory rhythm of Gamma Amino Butyric Acid (GABA) have also been implicated in sleep abnormality [118]. Like circadian disruption, prolonged exposure to ambient light may increase sleep latency. Light is known to suppress nocturnal melatonin synthesis making initiation of sleep difficult. Blue light has been shown to exert the greatest suppressive effect on melatonin secretion [117]. Light-related suppression in melatonin is due to a reduction in postganglionic noradrenergic neural discharge to the pineal gland. The ability of light to suppress melatonin secretion is known as the negative masking effect of light.

In summary, the review highlighted the possible mechanisms that underlie sleep anomaly that characterized frontline COVID-19 workers using existing information from experimental studies. Presence of CLOCK rs1801260 locus bearing TC and CLOCK rs680524 bearing GC and CC and stress-induced elevation of cannabinoid receptors, depletion of adenosine and forebrain derived neurotrophic factor, depletion of hippocampal glycogen and a rise in nitric oxide suppress spontaneous thalamic discharges which are involved in sleep induction are possible underlying mechanisms.

### **14. Conclusion**

COVID-19 emergence and the attendant waves of responses from frontline healthcare officers have been very remarkable. The review has highlighted the possible underlying mechanisms associated with occupational stress-induced sleep disorders in frontline healthcare providers managing COVID-19. It is very glaring from primary studies that COVID-19-induced occupational stress causes sleep disorders most especially insomnia in both male and female frontline healthcare workers which are connectable to a number of underlying factors including anxiety leading to neuroimmunological changes. Anxiety-associated sleep anomaly is attributable to stimulation of the reticular activating system which occurs as a result of activation of noradrenergic fiber and sympatho-adrenal axis. Depletion of hippocampal and brain glycogen by anxiety-induced activation of corticotropin releasing hormone (CRH)-secreting brain neurons and hypothalamic-corticotropic-adrenal cortex axis are important implicating mechanisms. Spontaneous discharge of noradrenergic fiber during basal state and changes in the normal secretory rhythm of hypnosis-related chemical messengers may be responsible for hypertension- and chronobiological disruption-induced sleep disorders respectively. Lastly, prolonged light exposure-induced suppression of melatonin secretion may elicit disruption of normal circadian sleep.

### **Conflict of interest**

The authors declare no conflict of interest.
