Putative contributions of circadian clock and sleep in the context of SARS-CoV-2 infection

Putative contributions of circadian clock and sleep in the context of SARS-CoV-2 infection

Miguel Meira eCruz, Masaaki Miyazawa, David Gozal

European Respiratory Journal Jan 2020, 2001023; 

DOI: 10.1183/13993003.01023-2020

Circadian deregulation and poor or insufficient sleep may facilitate COVID19 infection and severity

SARS coronavirus 2 (SARS-CoV-2), the etiologic agent of the pandemic coronavirus disease 2019 (COVID-19), is a newly found member of the Coronaviridae family, and is closely related to, albeit with important differences from, the severe acute respiratory syndrome coronavirus (SARS-CoV) [1]. It enters human cells through the binding of surface spike (S) glycoprotein with angiotensin converting enzyme 2 (ACE2) [24]. The distal S1 subunit of the S protein is responsible for receptor binding while the transmembrane S2 subunit mediates fusion between viral envelope and target cell membrane following proteolytic cleavage by specific cellular enzymes such as serine protease TMPRSS2 for S protein priming [5]. As expression levels of ACE2 likely affect the efficiency of virus attachment and entry as well as disease severity [6], and the interactions between viral S protein and ACE2 may directly cause lung injury [7], ACE2 can be a potential target of therapeutic and preventative interventions [8].


Sleep and SARS-Cov 2 infection

Sleep, a circadian behavioral manifestation of major regulatory homeostatic mechanisms such as those associated with immunity, has also been shown to interact with host defenses at the molecular and cellular levels. Indeed, extensive literature has indicated the important role of homeostatic sleep in innate and adaptive immunity [46]. Furthermore, there are clear reciprocal dependencies between sleep duration and quality and the immune responses against viral, bacterial, and parasitic pathogens, the latter altering in turn sleep patterns [46]. Thus, it is likely that improved sleep quality and duration in the population may mitigate the propagation and severity of disease induced by SASRS-Cov-2 infection. Interestingly and potentially relevant to the SARS-Cov-2-ACE2 pathophysiological interdependency, Carhan et al. observed in a drosophila model that adult flies lacking ACER (an ACE2 homologue in Drosophila melanogaster) or those treated with peptidase inhibitors experienced disrupted night-time sleep [47]. We are unaware of any specific studies examining the effects of sleep on SARS-Cov-2 infection. Nonetheless, we should remark that coronaviruses are found with increased frequency in the tonsillar tissues of children suffering from obstructive sleep apnea [48].

In summary, the unique potential links between SARS-Cov-2 and circadian rhythms and sleep have been reviewed, and suggest the possibility that both of these homeostatic processes may significantly modify the susceptibility to infection as well as the overall clinical manifestation of the disease. Therefore, implementation of healthy sleep measures as a protective strategy against infection, and early detection of patients at risk for more severe disease (e.g., night-shift workers or patients with OSA) may enable improved implementation of supportive measures and lead to better outcomes.


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