When the clock ticks wrong with COVID‐19

Abstract

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.

Association between Acute Respiratory Distress Syndrome Due to COVID-19 and Long-Term Sleep and Circadian Sleep–Wake Disorders

“…The causality of alteration to circadian rest-activity rhythms is unknown and is beyond the scope of this study. However, the circadian rest-activity rhythm may be affected due to the regulatory effect of the circadian clock over physiological functions in the human body such as respiratory function, immune system behavioral aspects, and the metabolic system [52]. In turn, owing to massive infection by pathogenic entities such as SARS-COV-2, these physiological functions are exhibited with alterations after ICU discharge [20,53].…”

“…In turn, owing to massive infection by pathogenic entities such as SARS-COV-2, these physiological functions are exhibited with alterations after ICU discharge [20,53]. Indeed, Papagerakis et al (2022) suggested potential connections between circadian rhythms, clock genes, and SARS-CoV-2 [52]. The additional analysis did not show any significant improvement in sleep and circadian rest-activity rhythm between the evaluated time points; such results may suggest that the effects of hospitalization and the acute phase of the disease are not the responsible for the sleep and circadian alterations.…”

“…The additional analysis did not show any significant improvement in sleep and circadian rest-activity rhythm between the evaluated time points; such results may suggest that the effects of hospitalization and the acute phase of the disease are not the responsible for the sleep and circadian alterations. Possible reasons for the maintenance of such alterations are: (i) they were already present before the infection; (ii) they are the consequence of other sequelae such as mental health, physical capacity, respiratory function; in fact, the persistence of factors such as neuromuscular symptoms [54], irregular behavior and lifestyles [52], pulmonary structural abnormalities and functional impairment [20], and neurocognitive impairment have been widely described in ICU survivors [54]. All these factors, in addition to the loss of synchronization between the central and peripheral clock, could potentiate long-term alterations in the circadian rest-activity rhythm twelve months after medical discharge [52].…”

“…Possible reasons for the maintenance of such alterations are: (i) they were already present before the infection; (ii) they are the consequence of other sequelae such as mental health, physical capacity, respiratory function; in fact, the persistence of factors such as neuromuscular symptoms [54], irregular behavior and lifestyles [52], pulmonary structural abnormalities and functional impairment [20], and neurocognitive impairment have been widely described in ICU survivors [54]. All these factors, in addition to the loss of synchronization between the central and peripheral clock, could potentiate long-term alterations in the circadian rest-activity rhythm twelve months after medical discharge [52]. Moreover, several studies suggested that physical treatment and rehabilitation play a significative role in the recovery of long COVID-19 patients, improving several aspects such as physical function, pain, and pulmonary and cognitive function [55][56][57].…”

Ionizing radiation altered the expression profiles and intracellular distribution of the circadian gene per1 in mouse brain neuronal cells

“…It receives time information from internal photosensitive retinal ganglion cells (ipRGCs) and is further transmitted through the retinohypothalamic tract (RHT) to ensure its synchronization to light/dark changes during the day [2,3] . Rhythm misalignment has been shown to increase the risk of metabolic syndrome [4] , cardiovascular disease [5] , cancer [6][7][8] , and even COVID-19 [9] .…”