Chronobiological changes due to school closures during the COVID-19 pandemic among adolescents in the DOrtmund Nutritional and Anthropometric Longitudinally Designed cohort study.

Due to the lockdown of schools as one of the COVID-19 control measures, adolescents have had the opportunity to re-organise their daily lives; e.g. some of them have adapted their bedtimes to the new situation during the lockdown in favour of their own chronotype. Hence, we investigated differences in chronobiological characteristics (e.g., the midpoint of sleep, sleep duration or social jetlag (SJL); i.e., a discrepancy between biological and social timing) before and during the pandemic lockdown to examine potential changes. We asked participants from the ongoing open cohort Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study to fill out the Munich Chronotype Questionnaire during the COVID-19 lockdown and received the information of participants (n = 66) during the pandemic. A reference group matched for age, season, and sex was randomly selected from the DONALD study to assess participants' chronobiological characteristics prior to (n = 132) the pandemic. Analyses of covariance were applied to examine differences between the two groups reflecting the situation before and during the COVID-19 pandemic. Participants were aged 9-18 years (52% males). In the current examination, average sleep duration across the week was higher among adolescents during the pandemic (ß = 00:30; p = 0.0006) and social jetlag was significantly lower (ß = -00:39; p < 0.0001). CONCLUSION: Our results showed that the COVID-19 lockdown enabled adolescents to adapt their sleeping habits according to their naturally late chronotype, which led to a significant reduction in SJL. These observations are likely to be explained by the effect of school closure. WHAT IS KNOWN: • Under 'normal conditions' without pandemic lockdowns, adolescents accumulate a lack of sleep due to social obligations such as school starts, resulting in social jetlag. • A late chronotype or exposure to social jetlag is a known risk factor for the development of chronic diseases. WHAT IS NEW: • The COVID-19 lockdown represents a 'natural experiment' that enables adolescents to adhere to their internal biological clock. Without the usual social obligations, social jetlag can be significantly reduced.

Delayed sleep phase disorder during the COVID-19 pandemic and its health implications.

Circadian rhythm sleep disorders are alterations that are characterized by a shift in the sleep-wake cycle relative to day and night, such as the delayed sleep phase disorder (DSPD), which is a retard of at least 2 hours in the sleep start. Typically, the patient falls asleep after 2 a.m. and wakes up after 10 a.m. and with symptom of sleep onset insomnia. The prevalence of DSPD in young adults is 0.48%, increasing to 3.3% in adolescents. Interestingly, patients with COVID-19 infection report anxiety due to the intensive care unit lockdown and constant exposure to bright light. In addition, post-COVID patients have an increased risk of developing DSPD. For example, in adolescent post-COVID patients, the prevalence of DSPD increases to 63.3%. Patients with DSPD also have alterations in metabolic health, poor school performance, cognitive impairment, and a higher risk of developing other diseases. The objective of the present review is therefore to describe the characteristics of DSPD during the COVID-19 pandemic and to outline its possible implications for physical health (eg, metabolism) and mental health (eg, anxiety or depression).

Chronotype influence on the effects of COVID-19 lockdown on sleep and psychological status in France.

The present study aims to assess the influence of chronotype on lockdown-induced effects on sleep and psychological outcomes. A total of 1671 participants were recruited in France and filled out online questionnaires about their sleeping hours and sleep quality, their chronotype (morning, intermediate, evening type), and their depressive, anxiety and stress symptoms both retrospectively (before lockdown) and currently (during the lockdown). Statistical analyses estimated the chronotype effect on the impact of the lockdown on sleep and psychological outcomes. Results show that during the lockdown, sleep quality decreased, sleep duration increased, and sleep midpoint was delayed and, while fatigue perception decreased, anxiety and depression increased. The decrease in sleep quality varied according to the participants' chronotype. The evening type's sleep quality decreased the most. A similar chronotype effect was also observed on sleep duration and sleep midpoint. Evening-type participants also increased their depressive symptoms. These results suggest that evening-type individuals have lower resilience to lockdown effect on psychological status and sleep pattern.

The Association of Time of Day of ChAdOx1 nCoV-19 Vaccine Administration With SARS-CoV-2 Anti-Spike IgG Antibody Levels: An Exploratory Observational Study.

Data from human and animal studies are highly suggestive of an influence of time of day of vaccine administration on host immune responses. In this population-based study, we aimed to investigate the effect of time of day of administration of a COVID-19 vector vaccine, ChAdOx1 nCoV-19 (AstraZeneca), on SARS-CoV-2 anti-spike S1 immunoglobulin (IgG) levels. Participants were 803 university employees who received their first vaccine dose in March 2021, had serology data at baseline and at 3 weeks, and were seronegative at baseline. Antibody levels were determined in binding antibody units (BAU/mL) using enzyme-linked immunosorbent assay (ELISA). Generalized additive models (GAM) and linear regression were used to evaluate the association of time of day of vaccination continuously and in hourly bins with antibody levels at 3 weeks. Participants had a mean age of 42 years (SD: 12; range: 21-74) and 60% were female. Time of day of vaccination was associated non-linearly ("reverse J-shape") with antibody levels. Morning vaccination was associated with the highest (9:00-10:00 h: mean 292.1 BAU/mL; SD: 262.1), early afternoon vaccination with the lowest (12:00-13:00 h: mean 217.3 BAU/mL; SD: 153.6), and late afternoon vaccination with intermediate (14:00-15:00 h: mean 280.7 BAU/mL; SD: 262.4) antibody levels. Antibody levels induced by 12:00-13:00 h vaccination (but not other time intervals) were significantly lower compared to 9:00-10:00 h vaccination after adjusting for potential confounders (beta coefficient = -75.8, 95% confidence interval [CI] = -131.3, -20.4). Our findings show that time of day of vaccination against SARS-CoV-2 has an impact on the magnitude of IgG antibody levels at 3 weeks. Whether this difference persists after booster vaccine doses and whether it influences the level of protection against COVID-19 needs further evaluation.

Monkeypox virus replication underlying circadian rhythm networks.

The mammalian brain has an endogenous central circadian clock that regulates central and peripheral cellular activities. At the molecular level, this day-night cycle induces the expression of upstream and downstream transcription factors that influence the immune system and the severity of viral infections over time. In addition, there are also circadian effects on host tolerance pathways. This stimulates adaptation to normal changes in environmental conditions and requirements (including light and food). These rhythms influence the pharmacokinetics and efficacy of therapeutic drugs and vaccines. The importance of circadian systems in regulating viral infections and the host response to viruses is currently of great importance for clinical management. With the knowledge gained from the COVID-19 pandemic, it is important to address any outbreak of viral infection that could become endemic and to quickly focus research on any knowledge gaps. For example, responses to booster vaccination COVID-19 may have different time-dependent patterns during circadian cycles. There may be a link between reactivation of latently infected viruses and regulation of circadian rhythms. In addition, mammals may show different seasonal antiviral responses in winter and summer. This article discusses the importance of the host circadian clock during monkeypox infection and immune system interactions.

Is there a diurnal variation of COVID-19 patients warranting presentation to the health centre? A chronobiological observational cross-sectional study.

BACKGROUND: The circadian clock regulates the function of the immune system, the replication of viruses, and the magnitude of infections. The aim of this study was to analyse whether hospital attendance in Coronavirus disease 2019 (COVID-19) patients presents a diurnal variation. METHODS: Data from the electronic medical records of 1094 COVID-19 patients who presented to a Health Centre in Qatar during the month of July 2020 was retrospectively analysed. The following demographic (i.e. time of day (TOD), sex, age), clinical (i.e. cycle threshold (CT), temperature, oxy-haemoglobin saturation and resting heart-rate), biochemical (i.e. uraemia, glycaemia and albuminia) and haematological (i.e. leukocytes, erythrocytes ad platelets) parameters were collected. RESULTS: Univariate analysis showed a significant effect of TOD on hospital admission (p < 0.001), with patients attending the health care centre more during the active behavioural phase (08h00-00h00) compared to the resting phase (00h00-08h00). COVID-19 infection blunted the circadian rhythms of core body temperature, neutrophils and leukocytes family and shifted the circadian rhythms of resting heart-rate and uraemia. Correlation analysis showed a near perfect negative correlation between the age of patients and the TOD (r=-0.97), with older patients attending the care centre earlier during the day. CONCLUSION: COVID-19 infection affected the circadian rhythms of the host through disrupting the circadian rhythms of core temperature and innate immunity mediators. Old patients attend the health care centre earlier compared to younger ones. However, CT during polymerase chain reaction-test was unaffected by the TOD, which limits the conclusion that COVID-19 viral infection exhibits diurnal variation.

Transcutaneous Electrical Cranial-Auricular Stimulation (Tecas) for Treatment of Insomnia Disorder with Comorbid Major Depressive Disorder: A Case Series: E-Poster Viewing

Introduction: Insomnia disorder (ID) and major depressive disorder (MDD) are highly comorbid, above 80% of MDD patients have insomnia disorder. Acupuncture as a major complementary and alternative medicine (CAM) therapy, is utilized extensively in Asia to treat mental health disorders.Transcutaneous electrical cranial-auricular stimulation (TECAS) is a potential new type of acupuncture treatment for MDD and ID which combines the scalp points and auricular points most commonly used by acupuncturists. It has the advantages of portability, quantifiable stimulation parameters and comfort, especially for home treatment under the normal situation of COVID-19, which can avoid the risk of infection due to frequent hospital trips. Materials / Methods: 10 ID-MDD patients were treated by TECAS which was administered at the bilateral auricular acupoints, Bai Hui (GV-20) and Yin Tang (GV-29) (waveform:4/20 Hz, wave width: 0.2ms+/-30%) for twice a day last 8 weeks. Pittsburgh Sleep Quality Index (PSQI) and Hamilton Depression Rating Scale(HAMD) of ID-MDD patients were evaluated before and after treatment. Result(s): HAMD-17 scores of 10 patients were lower at 4 and 8 weeks than before TECAS treatment, and the reduction was greater at 4 weeks than at 8 weeks. PSQI scores of 8 patients decreased at 4 and 8 weeks compared with before treatment, and the decrease was greater in the fourth week than in the 8th week. Insomnia of 2 patients improved at 4 weeks of treatment, but became worse in the 8th week as before treatment.7 out of 10 patients showed full insomnia response (50% reduction in PSQI) and 8 patients showed full depression response (50% reduction in HAMD-17 scores). Discussion(s): We suggest TECAS is a good therapeutic strategy to modulate the vagus nerve and trigeminal nerve propagate through electrical stimulation projected by neurons from peripheral sites to the central nervous system. Furthermore, we speculate that TECAS can make the trigeminal nerve afferent fibers and vagus nerve auricular branch carry messages from head facial stimulation to NTS, locus coeruleus, raphe nucleus, medullary reticular activating system and structure of the thalamus, and then to feel, edge, cortical and subcortical structures, so the electrical stimulation subcortical can cause direct regulation, namely the change of cortical excitability. Conclusion(s): These preliminary results in this group of CID-MDD patients are encouraging and need to be replicated in prospective sham-controlled studies with larger sample sizes. In addition, for patients with insomnia and depression, it is important to consider combining TECAS with psychotherapy to avoid the interference of acute negative emergency events. Acknowledgements: The support of National Key R&D Program of China (No.2018YFC1705800) and Key Laboratory of Acupuncture and Chronobiology of Sichuan Province(No.2021004) for this project is gratefully acknowledged. Learning Objectives: 1. To provide a new non-drug method for acupuncture treatment of insomnia and depression;2. Provide preliminary experimental results for the large-sample experimental design of TECAS for the treatment of insomnia and depression;3. Compared with previous studies on insomnia and depression, the regularity and characteristics of TECAS in treating insomnia and depression were found. Keywords: Transcutaneous Electrical Cranial-Auricular Stimulation (TECAS), insomnia disorder, a case series, acupuncture, Major Depressive Disorder Copyright © 2022

Holistic Needs Assessment of Cancer Survivors-Supporting the Process Through Digital Monitoring of Circadian Physiology.

The year 2022 could represent a significant juncture in the incorporation of mHealth solutions in routine cancer care. With the recent global COVID-19 pandemic leading a surge in both observation- and intervention-based studies predominantly aimed at remote monitoring there has been huge intellectual investment in developing platforms able to provide real time analytics that are readily usable. Another fallout from the pandemic has seen record waiting times and delayed access to cancer therapies leading to exhausting pressures on global healthcare providers. It seems an opportune time to utilize this boom in platforms to offer more efficient "at home" clinical assessments and less "in department" time for patients. Here, we will focus specifically on the role of digital tools around cancer survivorship, a relevant aspect of the cancer journey, particularly benefiting from integrative approaches. Within that context a further concept will be introduced and that is of the likely upsurge in circadian-based interpretation of continuous monitoring and the engendered therapeutic modifications. Chronobiology across the 24-hour span has long been understood to control key bodily aspects and circadian dysregulation plays a significant role in the risk of cancer and also the response to therapy and therefore progressive outcome. The rapid improvement in minimally invasive monitoring devices is, in the opinion of the authors, likely to advance introducing chronobiological amendments to routine clinical practices with positive impact on cancer survivors.

The role of BDNF Val66Met polymorphism in circadian rhythm variation and attention in adolescents

Introduction: Adolescents' cognitive performance is impacted by factors such as sleep habits, chronotypes and also genetic characteristics. The periods of human sleep and wakefulness are controlled by homeostatic and circadian factors, which the combination generates variations in the preferences for hours of activity and rest, called chronotypes. Chronotypic classification impacts cognitive skills such as logic and problem solving. In adolescence, there is a greater tendency to evening chronotype. The neural factor called BDNF, Brain- Derived Neurotrophic Factor, showed a significant role in cognitive performance variations as in different sleep patterns. The human BDNF gene has a frequent polymorphism called Val66Met, related to several cognitive functions and different patterns of sleep and circadian rhythm. Objective: Evaluate the association of BDNF Val66Met polymorphism with circadian patterns and cognitive performance on tests of attention, in high school students. Methods: High school students, aged between 15 and 17 years old were included in the study, whose cognitive attention skills were investigated by the Psychological Battery for Assessment of Attention. Their BDNF genotypes were determined by analyzing self-collected oral cell samples, which were amplified by real-time PCR using fluorescent probes. Chronotypic characteristics were evaluated by completing two morningness and eveningness scales. Because of the pandemic of COVID-19, a questionnaire about the presence of symptoms, in the previous days of the tests, was included. At present, volunteers are being evaluated through actigraphy. Results: Eighty-five adolescents were evaluated in that study. The average attention score of students who study in the afternoon was lower than individuals who study in the morning. The average score attention for the female gender was significantly lower than that obtained for the male gender. The students who reported symptoms of COVID- 19 had a significantly lower attention score. Lastly, there was no correlation between the chronotype defined by the scales, the performance in the attention test, or even the BDNF genotype of the participants. Conclusion: The central findings obtained, in the first phase of the study, complement the understanding of the associations between the parameters of cognition, chronobiology and genetic aspects. In the next phase, the use of actigraphy will make it possible to deepen these analyzes and conclusions.

Variability of Mortality: Additional Information on Mortality and Morbidity Curves under Normal and Pathological Conditions [Commentary on the Article by A. G. Malygin "Programmed Risks of Death in Male Patients with Diabetes" Published in Biochemistry (Moscow), vol. 86, pp. 1553-1562 (2021)].

Analysis of demographic data indicates uneven distribution of mortality within a year, month, and even week time period. This is of great practical importance for the operation of medical institutions, including intensive care units, and makes it possible to calculate economic and labor requirements of medical institutions. All the above is especially relevant during the era of the COVID-19 pandemic. Malygin showed the presence of one to two fluctuations per week in the mortality of male patients with type 2 diabetes. The height of the peaks of such fluctuations is determined, as expected, by the regular parameter indicating their position on the axis of lifespan and random parameter reflecting adverse effects of external environmental factors on the body, as well as the extent of the periodically occurring sharp decrease in the nonspecific resistance. This article discusses results of recent research in the field of small (semi-weekly, weekly, monthly, and seasonal) fluctuations of mortality. Based on a large array of accumulated data, it can be concluded that the decrease in seasonal variability of mortality accompanies an increase in the life expectancy. Studying characteristics of mortality fluctuations makes it possible to move from investigating the impact of biorhythms (Master Clock) on the development of acute and chronic phenoptotic processes directly to studying the patterns of mortality rhythms themselves (rhythms of phenoptosis).

A Study on Chronofatality Trends of COVID-19 Deaths at a Tertiary Care Hospital

The aim of the study is to find out any association between time of death in coronavirus disease (COVID-19) patients and variables like age, sex, and existence of comorbidities including type II diabetes mellitus, hypertension, coronary artery disease, chronic kidney disease, etc. An attempt was also made to elucidate the reasons for relationship between time of death and other aforementioned variables. Mortality data of 1,553 COVID-19 cases from a tertiary care hospital between March 2020 to September 2021 were analyzed. Maximum deaths occurred between 18:01 hours to 06:00 hours of the 24-hour cycle. There is a significant statistical association between time of death and age, time of death and sex, time of death and having a comorbidity of diabetes mellitus in the study sample. The study confirms that the chronofatality of COVID-19 deaths has a nocturnal predilection. The circadian rhythms of glucocorticoids, respiratory physiology of sleep, and circadian hemodynamic variations may have a role in prognosis and fatality of COVID-19. © This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/bync/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © 2021 Korean Academy of Sleep Medicine

Screen media use and sleep patterns in Spanish adolescents during the lockdown of the coronavirus pandemic.

PURPOSE: The aim of this study was to investigate screen media use and sleep patterns among Spanish adolescents during the lockdown (LD) of the first peak of the coronavirus pandemic. METHODS: Cross-sectional community-based study of adolescents aged 11-18 years. An online questionnaire with queries about screen time, sleep, and other healthy habits was completed by parents or guardians. RESULTS: Overall 265 adolescents were enrolled. The mean age was 13.6 ± 2.3 years, 58% were boys, 68% were in secondary school and 72% lived in urban areas. Before the LD (BLD) 87% of adolescents used electronic devices < 4 h/d, while during the LD (DLD) screen time was > 4 h/d in 75% of cases (p < 0.0001). A delayed wake time and bedtime weekdays (BLD wake time weekdays: later than 09:45 0.0% vs. DLD 30%, p < 0.0001, and BLD bedtime weekdays: later than 00:30 3% vs. DLD 35%, p < 0.0001) and weekends DLD was observed. Adolescents who used electronic devices > 4 h/d DLD compared with those who used < 4 h/d reported more frequently long sleep latency (93% vs. 7%, p = 0.007), low sunlight exposure (77% vs. 23%, p = 0.031), less physical activity (86%. vs. 15%, p = 0.011) and weight gain (78%. vs. 22%, p = 0.049). CONCLUSIONS: During the lockdown Spanish adolescents reported elevated screen time and delayed sleep patterns. An increase in screen media use was associated with unhealthy habits.

Nutritional and Behavioral Approaches to Body Composition and Low-Grade Chronic Inflammation Management for Older Adults in the Ordinary and COVID-19 Times.

As more insight is gained into personalized health care, the importance of personalized nutritional and behavioral approaches is even more relevant in the COVID-19 era, in addition to the need for further elucidation regarding several diseases/conditions. One of these concerning body composition (in this context; bone, lean and adipose tissue) is osteosarcopenic adiposity (OSA) syndrome. OSA occurs most often with aging, but also in cases of some chronic diseases and is exacerbated with the presence of low-grade chronic inflammation (LGCI). OSA has been associated with poor nutrition, metabolic disorders and diminished functional abilities. This paper addresses various influences on OSA and LGCI, as well as their mutual action on each other, and provides nutritional and behavioral approaches which could be personalized to help with either preventing or managing OSA and LGCI in general, and specifically in the time of the COVID-19 pandemic. Addressed in more detail are nutritional recommendations for and roles of macro- and micronutrients and bioactive food components; the microbiome; and optimal physical activity regimens. Other issues, such as food insecurity and nutritional inadequacy, circadian misalignment and shift workers are addressed as well. Since there is still a lack of longer-term primary studies in COVID-19 patients (either acute or recovered) and interventions for OSA improvement, this discussion is based on the existing knowledge, scientific hypotheses and observations derived from similar conditions or studies just being published at the time of this writing.

SARS-CoV-2/COVID-19 and physical distancing: risk for circadian rhythm dysregulation, advice to alleviate it, and natural experiment research opportunities.

SARS-CoV-2/COVID-19 leads to numerous unplanned or natural experiments with health and disease. Physical (social) distancing - a counter-measure with no alternative, but with no precedence in scope and scale either - is a key intervention and trigger of natural experiments. From a practical perspective, concerned disciplines should increase awareness of, provide recommendations to meet, and develop research for, health challenges arising from physical distancing at home. From the field of chronobiology, prolonged home stays may place undue strain on the body's circadian timing system but straightforward and often underestimated advice for coping can be provided (herein we provide such advice). Of course, advice or recommendations from other concerned disciplines that identify challenges associated with current COVID-19 mitigation strategies are also needed. From a research perspective, different disciplines should rise to the occasion and explore unsuspected natural experiment angles toward novel insights to promote health and prevent disease.