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Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a member of the coronavirus family that causes the novel coronavirus disease first diagnosed in 2019 (COVID‐19). Although many studies have been carried out in recent months to determine why the disease clinical presentations and outcomes can vary significantly from asymptomatic to severe or lethal, the underlying mechanisms are not fully understood. It is likely that unique individual characteristics can strongly influence the broad disease variability; thus, tailored diagnostic and therapeutic approaches are needed to improve clinical outcomes. The circadian clock is a critical regulatory mechanism orchestrating major physiological and pathological processes. It is generally accepted that more than half of the cell‐specific genes in any given organ are under circadian control. Although it is known that a specific role of the circadian clock is to coordinate the immune system's steady‐state function and response to infectious threats, the links between the circadian clock and SARS‐CoV‐2 infection are only now emerging. How inter‐individual variability of the circadian profile and its dysregulation may play a role in the differences noted in the COVID‐19‐related disease presentations, and outcome remains largely underinvestigated. This review summarizes the current evidence on the potential links between circadian clock dysregulation and SARS‐CoV‐2 infection susceptibility, disease presentation and progression, and clinical outcomes. Further research in this area may contribute towards novel circadian‐centred prognostic, diagnostic and therapeutic approaches for COVID‐19 in the era of precision health. [ABSTRACT FROM AUTHOR]

Salivary melatonin is a clinically used biomarker for diagnosing circadian rhythm sleep disorders. Current melatonin detection assays are complex, expensive, and in many cases do not adequately measure low levels of salivary melatonin. Precisely measuring melatonin levels at multiple time points is crucial for determining dim light melatonin onset to evaluate its circadian fluctuation as well as the extent of circadian disruption and consequently adapt treatment regimens. Moreover, melatonin low levels in saliva challenges the reliability of routine clinical testing. This paper presents the development of a novel, highly sensitive, yet cost-effective, colorimetric assay for the rapid detection of salivary melatonin utilizing aptamer-AuNPs. Among several types of the aptamer tested, the 36-mer MLT-A-2 aptamer-AuNP probe showed the highest sensitivity with a melatonin limit of detection of 0.0011 nM along with a limit of quantification of 0.0021 nM in saliva. Moreover, our assay showed preferential interaction with melatonin when tested in presence of other structurally similar counter-targets. Taken together, this study provides new parameters for a melatonin assay that meets adequate levels of sensitivity and selectivity. The developed colorimetric assay could be adapted in a point-of-care system for profiling salivary melatonin levels at multiple time points during 24 h, crucial for accurately diagnosing and monitoring circadian rhythm sleep disorders and beyond. [Display omitted] • The ultralow level of salivary melatonin detected using an aptamer-AuNP probe based assay. • Aptamers have a salt dependency for their structural change and melatonin binding. • Truncated 36-mer MLT-A-2 aptamer-AuNP showed high sensitivity with LOD = 0.0011 nM. • Assay showed high specificity and selectivity in the presence of counter-targets. [ABSTRACT FROM AUTHOR]

The internally driven 24-h cycle in humans, called circadian rhythm, controls physiological, metabolic, and hormonal processes, and is tied to the circadian clocks ticking in most of the cells and tissues. The central clock, located in suprachiasmatic nuclei of the hypothalamus, is directly influenced by external cues, particularly light, and entrains the peripheral clocks through neural and hormonal pathways to the external light-dark cycle. However, peripheral clocks also have self-sustained circadian rhythmicity and feeding is the potent synchronizer. The internal clock system regulates the sleep-wake cycle and maintains stress responses through the hypothalamus-pituitary-adrenal axis and autonomic pathways. Any misalignment in this complex network could lead to circadian clock disruption and endocrine and metabolic dysfunction that may induce inflammatory responses. The detrimental consequences of such dysfunction are broad and can lead to serious health problems; however, the extent of the circadian disruption is difficult to assess. New promising techniques based on biosensors and point-of-care devices using aptamers - single-stranded DNA or RNA biorecognition molecules that can measure biomarkers of stress, sleep, and circadian rhythms in bodily fluids such as saliva with high sensitivity and specificity - can provide timely and accurate diagnosis and allow for effective implementation of behavioral and therapeutic interventions. This review provides detailed insight into the complex crosstalk between stress, sleep, and circadian rhythm, their relationship with the body's homeostasis, and the consequences of circadian dysregulation. The review also summarizes the mechanisms of aptamer-based biosensors and/or point-of-care devices developed to date for the detection of salivary biomarkers linked to stress, sleep, and circadian rhythm. Lastly, the review outlines the knowledge gaps in the literature related to the detection of lower concentrations of biomarkers in saliva and discusses the prospects of aptamer-based detection of salivary biomarkers from a high-precision perspective that is crucial for clinical diagnosis, at a time when circadian disruption is evident in unprecedented proportions across the globe. [ABSTRACT FROM AUTHOR]