Coronavirus disease 2019 (COVID-19) has been associated with an increase in sleeping-related matters, exactly insomnia [1]. Terms as COVID-somnia, coronasomnia or covidsomnia have been formulated worldwide by tracking mental health responses to the novel coronavirus [1]. Coronasomnia represents a sleeplessness condition connected with severe and long-term health impacts due to COVID-19 pandemic [1]. Insomnia is the result of a complex relationship between psychological cognitive arousal, damaged circadian clock, and sleep homeostatic mechanisms [1]. Chronic insomnia is a painful condition characterized by an important morbidity, reduced productivity, increases risk of accidents, and poor quality of life [2]. Therapeutic approach to insomnia comprises drug and behavioural therapy, but they have limitations [2]. Recently, oral nicotinamide mononucleotide (NMN) supplement has been proposed as a new treatment for chronic insomnia for its peculiarity to effectively restore nicotinamide adenine dinucleotide (NAD+) levels [2]. The sentinel metabolite NAD+ is necessary for Sirtuin1 (SIRT1) activity [2]. Sirtuins are a subtype of a conserved family of (NAD)-dependent protein deacetylases that can control different functions at different cellular locations such as transcription, genome stability, metabolism, and cell signaling [2]. The deacetylase SIRT1, encoded by the SIRT1 gene has been verified to control sleep through its relationship with wake–sleep neurotransmitters and somnogens [3]. SIRT1 has been evidenced to govern central circadian control in the brain by activating the transcription of the two major circadian regulators, BMAL1 and CLOCK [3]. Homeostatic process appears to be an essential regulatory mechanism for sleep [3]. Interestingly, SIRT1 has also been proposed to contribute to sleep homeostasis [4]. Intriguingly, inhibition of SIRT1 has been included among the molecular pathology pathway of COVID-19 infection leading to inflammatory processes [4]. Hyperinflammation described in COVID-19 has been related to to a significant reduction in cellular NAD+ stores implying that NAD+ represents a key player in COVID-19 pathophysiology [5]. NAD+ is considered a modulator of viral infection outcomes [5]. Depletion of NAD+ has been linked to COVID-19 [5]. It has been suggested that NAD+ metabolic pathway is under increased demand during COVID-19 infection [5]. Moreover, NAD+ concentrations in tissues and organs have been recognized to be lower in patients with severe COVID-19 symptoms when compared with healthy individuals [4]. Taken together, we suppose that covidsomnia may be the consequence of the decline of NAD+ by COVID-19 infection leading to decreased activity of SIRT1 with a negative impact on the two major circadian regulators, BMAL1 and CLOCK. Given that SIRT1 appears to play an important role in sleep regulation, there may be a need for further basic investigations to better define the molecular mechanisms underlying the SIRT1-NAD+ axis, as well as to develop safe and effective therapeutic strategies to restore SIRT1 activity among patients with covidsomnia.
Acknowledgements
In memory of Sossio Mormile.
Declarations
Conflict of interest
The author declares no potential conflicts of interest.
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