**11. Occupational stress-related sleep disorders IN frontline health workers during COVID-19 pandemic: roles of chronobiological disruption**

One of the important attributes of physiological processes is rhythmicity. Physiological processes occur in distinct patterns, reaching peak level (acrophase) at a phase of 24 hour day and nadir (bathophase) during the other phase of 24 hour day. The periodic variation in physiological processes is known as chronobiology. Some processes are completed (reaching both acrophase and bathophase) in appropriately 24 hours (circadian rhythms). Others require either less than 24 hours (ultradian rhythms) or greater than 24 hour (infradian rhythms) to be completed [105]. Interestingly, all internal biological rhythms are serviced by external rhythms which can range from environmental factors to physico-mental situations like occupational demand. Studies from shift workers are enormous in support of the deleterious impact of work schedules on sleep pattern and body temperature (circadian), hormone secretions (ultradian and circadian), and reproductive cycle (infradian). Wan and Chung [106] showed that nurses on a rotatory schedule had a greater proportion of irregular ovarian cycle. In Sweden, midwives on irregular duty schedules showed reduced fecundity.

In Night shift workers, there was a change in the timing of LH surge [107–109]. Ning et al. [110] reported that oil workers on different work schedules exhibited sleep disorders and noted that cortisol level, Per3 gene, and rs680 loci of CLOCK influence sleep quality in these workers. Specifically, they discovered that CLOCK rs1801260 locus bearing TC and CLOCK rs680524 bearing GC and CC exhibited lower sleep disorders. The change in sleep pattern reported by Ning et al*.* [110] and many other investigators are significant viewing from the perspectives of the human activity cycle. Human beings are diurnal, designed to be active in the daytime and passive at night, working during the daytime and resting in the nighttime. Prolongation of working period to nighttime due to need, incentive, or disease adversely affects sleep quantity and quality.

In people whose work schedules extend into night, the ascending reticular fibers continue to release excitatory neurotransmitters (norepinephrine, epinephrine, serotonin, acetylcholine, histamine, orexin among others). Under the influence of these hormones, it is very difficult for sleep to be induced. In addition, shift workers experience changes in normal secretory pattern and rhythm of hypnotic hormones including melatonin, leptin, Gamma Amino Butyric Acid (GABA) among others [111]. This, in part, explains the importance of sleep hygiene. Sleep hygiene is simply defined as a sleep-promoting lifestyle. One of these lifestyles is voluntary withdrawal from active engagements [107, 109, 112]. Prolongation of activity is not only common in workers. Students exhibit this habit before, during, and after examination or contest [107, 109]. Ghrelin and leptin are chemical messengers that strongly influence feeding patterns and sleep and their secretions follow circadian pattern. Ghrelin peaks in the daytime and falls in the nighttime while leptin rises during nighttime/ sleep and falls in daytime (usually in the absence of meal ingestion), respectively [113]. In people whose activities extend into night, nocturnal secretions of ghrelin and leptin rise and fall respectively. This results in hunger perception and nighttime eating which culminate in sleep and health problems. People who travel across latitude and shift workers exhibit a deranged sleep/wakefulness cycle [114, 115]. Other health issues that may co-exist with deranged sleep/wakefulness cycle include mood disorders, cardiovascular diseases, menstrual cycle anomaly, and breast cancer risk [116, 117].

In addition to leptin, disruption of secretory rhythm of Gamma Amino Butyric Acid (GABA) may be implicated in sleep abnormality [118]. A study by Junkermann et al. [119] supports the possibility that night work induced- alteration in progesterone secretory rhythm may participate in sleep abnormality that characterizes frontline COVID-19 health workers.
