Clocks, Viruses, and Immunity: Lessons for the COVID-19 Pandemic

Sengupta, Shaon; Ince, Louise; Sartor, Francesca; Borrmann, Helene; Zhuang, Xiaodong; Naik, Amruta; Curtis, Annie M.; McKeating, Jane A.

doi:10.1177/0748730420987669

Cited by 31 publications

(21 citation statements)

References 107 publications

(131 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A key finding from our study is the potential application of chronomodifying drugs for the treatment of SARS-CoV-2 infection (Sengupta et al, 2021). Dexamethasone is one of the few drugs that can reduce the severity of COVID-19 (Group et al, 2020) and is known to synchronise circadian pathways (Oster et al, 2006;Pezuk et al, 2012).…”

mentioning

confidence: 77%

“…Influenza A infection of arrhythmic mice, lacking BMAL1, is associated with a higher viral burden in the lung (Edgar et al, 2016) and elevated inflammatory responses (Ehlers et al, 2018;Sengupta et al, 2019). We (Sengupta et al, 2021) and others (Maiese, 2020;Ray and Reddy, 2020) hypothesized a potential role for the circadian clock in COVID-19. To investigate a potential role for circadian pathways in the SARS-CoV-2 life cycle we assessed whether infection was time-dependent in Calu-3 lung epithelial cells.…”

mentioning

confidence: 85%

See 1 more Smart Citation

The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells

Zhuang

Tsukuda

Wrensch

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

The COVID-19 pandemic, caused by SARS-CoV-2 coronavirus, is a global health issue with unprecedented challenges for public health. SARS-CoV-2 primarily infects cells of the respiratory tract, via binding human angiotensin-converting enzyme (ACE2), and infection can result in pneumonia and acute respiratory distress syndrome. Circadian rhythms coordinate an organisms response to its environment and recent studies report a role for the circadian clock to regulate host susceptibility to virus infection. Influenza A infection of arhythmic mice, lacking the circadian component BMAL1, results in higher viral replication and elevated inflammatory responses leading to more severe bronchitis, highlighting the impact of circadian pathways in respiratory function. We demonstrate circadian regulation of ACE2 in lung epithelial cells and show that silencing BMAL1 or treatment with the synthetic REV-ERB agonist SR9009 reduces ACE2 expression and inhibits SARS-CoV-2 entry and RNA replication. Treating infected cells with SR9009 limits viral replication and secretion of infectious particles, showing that post-entry steps in the viral life cycle are influenced by the circadian system. Our study suggests new approaches to understand and improve therapeutic targeting of COVID-19.

show abstract

mentioning

confidence: 77%

mentioning

confidence: 85%

The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells

Zhuang

Tsukuda

Wrensch

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…The COVID-19 pandemic provides a unique opportunity to test the effects of social and mobility changes on wellbeing. Importantly, these effects may also indirectly affect the immune system: sleep, biological rhythms and wellbeing are all interconnected, and affect our immune system function and ability to fight viral infections [28][29][30][31][32][33][34]. Therefore, understanding these relations may also help us develop protective recommendations for reducing the risk of infection and improve vaccination outcomes [33], which may be different for different subpopulations.…”

Section: Introductionmentioning

confidence: 99%

Differential effects of COVID-19 lockdowns on well-being: interaction between age, gender and chronotype

Oved

Mofaz

Lan

et al. 2021

J. R. Soc. Interface.

View full text Add to dashboard Cite

The unprecedented restrictions imposed due to the COVID-19 pandemic altered our daily habits and severely affected our well-being and physiology. The effect of these changes is yet to be fully understood. Here, we analysed highly detailed data on 169 participants for two to six months, before and during the second COVID-19 lockdown in Israel. We extracted 12 well-being indicators from sensory data of smartwatches and from self-reported questionnaires, filled daily using a designated mobile application. We found that, in general, lockdowns resulted in significant changes in mood, sleep duration, sport duration, social encounters, resting heart rate and number of steps. Examining subpopulations, we found that younger participants (aged 20–40 years) suffered from a greater decline in mood and number of steps than older participants (aged 60–80 years). Likewise, women suffered from a higher increase in stress and reduction in social encounters than men. Younger early chronotypes did not increase their sleep duration and exhibited the highest drop in mood. Our findings underscore that while lockdowns severely impacted our well-being and physiology in general, greater damage has been identified in certain subpopulations. Accordingly, special attention should be given to younger people, who are usually not in the focus of social support, and to women.

show abstract

“…Interestingly, there is a growing related literature pointing out that the circadian rhythms which influences gene expression and many cellular and physiological parameters may influence individual susceptibility and resilience to viral infections which interacts with those circadian internal changes (Diallo et al, 2020;Sengupta et al, 2021). Antiviral therapies in COVID-19 patients are more efficient when provided in the morning as opposed to in the evening (De Giorgi et al, 2020), which is presumably independent from individuals chronotype.…”

Section: Implications For Public Policymentioning

confidence: 99%

COVID-19 Pandemic on Fire: Evolved Propensities for Nocturnal Activities as a Liability Against Epidemiological Control

et al. 2021

View full text Add to dashboard Cite

Humans have been using fire for hundreds of millennia, creating an ancestral expansion toward the nocturnal niche. The new adaptive challenges faced at night were recurrent enough to amplify existing psychological variation in our species. Night-time is dangerous and mysterious, so it selects for individuals with higher tendencies for paranoia, risk-taking, and sociability (because of security in numbers). During night-time, individuals are generally tired and show decreased self-control and increased impulsive behaviors. The lower visibility during night-time favors the partial concealment of identity and opens more opportunities for disinhibition of self-interested behaviors. Indeed, individuals with an evening-oriented chronotype are more paranoid, risk-taking, extraverted, impulsive, promiscuous, and have higher antisocial personality traits. However, under some circumstances, such as respiratory pandemics, the psychobehavioral traits favored by the nocturnal niche might be counter-productive, increasing contagion rates of a disease that can evade the behavioral immune system because its disease cues are often nonexistent or mild. The eveningness epidemiological liability hypothesis presented here suggests that during the COVID-19 pandemic, the evening-oriented psychobehavioral profile can have collectively harmful consequences: there is a clash of core tendencies between the nocturnal chronotype and the recent viral transmission-mitigating safety guidelines and rules. The pandemic safety protocols disrupt much normal social activity, particularly at night when making new social contacts is desired. The SARS-CoV-2 virus is contagious even in presymptomatic and asymptomatic individuals, which enables it to mostly evade our evolved contagious disease avoidance mechanisms. A growing body of research has indirectly shown that individual traits interfering with social distancing and anti-contagion measures are related to those of the nocturnal chronotype. Indeed, some of the social contexts that have been identified as superspreading events occur at night, such as in restaurants, bars, and nightclubs. Furthermore, nocturnal environmental conditions favor the survival of the SARS-CoV-2 virus much longer than daytime conditions. We compare the eveningness epidemiological liability hypothesis with other factors related to non-compliance with pandemic safety protocols, namely sex, age, and life history. Although there is not yet a direct link between the nocturnal chronotype and non-compliance with pandemic safety protocols, security measures and future empirical research should take this crucial evolutionary mismatch and adaptive metaproblem into account, and focus on how to avoid nocturnal individuals becoming superspreaders, offering secure alternatives for nocturnal social activities.

show abstract

Clocks, Viruses, and Immunity: Lessons for the COVID-19 Pandemic

Cited by 31 publications

References 107 publications

The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells

The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells

Differential effects of COVID-19 lockdowns on well-being: interaction between age, gender and chronotype

COVID-19 Pandemic on Fire: Evolved Propensities for Nocturnal Activities as a Liability Against Epidemiological Control

Contact Info

Product

Resources

About