The impact of blue light and digital screens on the skin.

INTRODUCTION: The skin is frequently subjected to a variety of environmental trauma and stress. It is unavoidably subjected to blue light due to the increased use of electronic equipment, including indoor lighting and digital gadgets like smartphones and laptops, which have a range of detrimental effects. The method of action and numerous harmful consequences of blue light on the skin are the main subjects of this review. MATERIALS AND METHODS: A literature search has been performed using PubMed, GoogleScholar and EmBase databases and an updated review on the topic has been presented. RESULTS: Numerous studies have shown that being exposed to blue light accelerates the aging process and produces cutaneous hyperpigmentation. It also modifies the circadian rhythm. The two main molecules that mediate cellular responses to blue light are nitric oxide (NO) and reactive oxygen species. However, the precise process is still not fully known. CONCLUSION: These negative consequences may eventually cause more general skin damage, which may hasten the aging process. At times, skin protection may be crucial for protection against blue light.

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.

The association of chronotype and social jet lag with body composition in German students: The role of physical activity behaviour and the impact of the pandemic lockdown.

Young adults with a later chronotype are vulnerable for a discrepancy in sleep rhythm between work- and free days, called social jet lag (SJL). This study analysed (i) chronotype/SJL association with visceral fat/skeletal muscle mass, (ii) the attribution to physical activity behaviour, and (iii) chronotype-specific changes in physical activity behaviour in young adults during the Covid-19 pandemic lockdown. Chronotype and SJL were derived from the Munich-Chrono-Type-Questionnaire in 320 German students (age 18-25 years) from September 2019 to January 2020, 156 of these participated in an online follow-up survey in June 2020. Body composition was assessed by bioimpedance analysis at baseline. Multivariable linear regression analyses were used to relate chronotype/SJL to body composition; the contribution of self-reported physical activity was tested by mediation analysis. At baseline, a later chronotype and a larger SJL were associated with a higher visceral fat mass (P<0.05), this relation was notably mediated by the attention to physical activity (P<0.05). Chronotype (P = 0.02) but not SJL (P = 0.87) was inversely associated with skeletal muscle mass. During the pandemic lockdown, chronotype hardly changed, but SJL was reduced. Timing and physical activity behaviour remained in most participants and changes were unrelated to chronotype (all P>0.07). A later chronotype/higher SJL may increase the risk of a higher visceral fat mass even in this relatively healthy sample, which may be partly due to their physical activity behaviour. Despite a reduction in SJL during the pandemic lockdown, later chronotypes did not change their physical activity behaviour more than earlier chronotypes.

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.

Association between Lifestyle- and Circadian Rhythm-Related Changes, and Different Depression Symptom Clusters during COVID-19.

BACKGROUND: The COVID-19 pandemic brought along a new situation for the population worldwide. The most important safety measures and lockdown expected extreme adaptability and flexibility impacting mental well-being. The aim of our study was to identify associations between changes in lifestyle and circadian rhythm and depression during the pandemic. SUBJECTS AND METHODS: Our analysis has been carried out on the Hungarian data set of the COMET-G study including information on lifestyle and circadian rhythm-associated factors and severity of depression and its 3 symptom clusters. Associations were assessed using linear regression models adjusted for age and sex. RESULTS: All variables reflecting changes in quality and quantity of sleep showed significant associations with overall depression scores and the three distinct symptom cluster scores. All variables reflecting importance and changes in physical activity during the pandemic were similarly significantly associated with all depression measures. However, only changes in quality of diet, but not quantity was associated with depression scores. CONCLUSIONS: Our results may confirm the association of circadian rhythm and lifestyle-related environmental factors in deterioration of mental health during COVID and help devise prevention and intervention methods and targets for similar situations.

Delayed circadian rhythms and insomnia symptoms in obsessive-compulsive disorder.

BACKGROUND: Accumulating evidence implicates sleep and circadian rhythm disturbance in obsessive-compulsive disorder (OCD). However, a multimethod characterization of sleep and circadian rhythms in OCD, their association with symptom severity, and the functional relationship between these variables is lacking. METHODS: The present study measured multiple indicators of sleep and circadian rhythms in a sample of adults with OCD, adults without OCD, and healthy controls (n = 74). Participants completed measures of morningness-eveningness, delayed sleep-wake phase disorder (DSWPD), insomnia symptoms, and OCD symptoms, as well as one week of sleep monitoring via a sleep diary and actigraphy. RESULTS: Delayed circadian rhythms (higher eveningness, later mid-sleep timing, and higher rates of DSWPD) and higher insomnia symptoms were observed in those with OCD compared to healthy controls, as well as associations between delayed circadian rhythms and insomnia symptoms and OCD symptom severity across the full sample. Further, insomnia symptoms mediated the relationship between delayed circadian rhythms and OCD symptoms. In contrast, there were no links between total sleep time or sleep quality and OCD. LIMITATIONS: Data collection during COVID-19 pandemic, correlational data, no physiological measure of circadian rhythms. CONCLUSIONS: These findings highlight a robust association between delayed circadian rhythms and OCD and suggest insomnia symptoms may be one mechanism in this relationship. Sleep and circadian rhythm disturbance may be novel targets for OCD treatment.

Understanding Cellular Redox Homeostasis: A Challenge for Precision Medicine.

Living organisms use a large repertoire of anabolic and catabolic reactions to maintain their physiological body functions, many of which include oxidation and reduction of substrates. The scientific field of redox biology tries to understand how redox homeostasis is regulated and maintained and which mechanisms are derailed in diverse pathological developments of diseases, where oxidative or reductive stress is an issue. The term "oxidative stress" is defined as an imbalance between the generation of oxidants and the local antioxidative defense. Key mediators of oxidative stress are reactive species derived from oxygen, nitrogen, and sulfur that are signal factors at physiological concentrations but can damage cellular macromolecules when they accumulate. However, therapeutical targeting of oxidative stress in disease has proven more difficult than previously expected. Major reasons for this are the very delicate cellular redox systems that differ in the subcellular compartments with regard to their concentrations and depending on the physiological or pathological status of cells and organelles (i.e., circadian rhythm, cell cycle, metabolic need, disease stadium). As reactive species are used as signaling molecules, non-targeted broad-spectrum antioxidants in many cases will fail their therapeutic aim. Precision medicine is called to remedy the situation.

Circadian patterns of heart rate, respiratory rate and skin temperature in hospitalized COVID-19 patients.

RATIONALE: Vital signs follow circadian patterns in both healthy volunteers and critically ill patients, which seem to be influenced by disease severity in the latter. In this study we explored the existence of circadian patterns in heart rate, respiratory rate and skin temperature of hospitalized COVID-19 patients, and aimed to explore differences in circadian rhythm amplitude during patient deterioration. METHODS: We performed a retrospective study of COVID-19 patients admitted to the general ward of a tertiary hospital between April 2020 and March 2021. Patients were continuously monitored using a wireless sensor and fingertip pulse oximeter. Data was divided into three cohorts: patients who recovered, patients who developed respiratory insufficiency and patients who died. For each cohort, a population mean cosinor model was fitted to detect rhythmicity. To assess changes in amplitude, a mixed-effect cosinor model was fitted. RESULTS: A total of 429 patients were monitored. Rhythmicity was observed in heartrate for the recovery cohort (p<0.001), respiratory insufficiency cohort (p<0.001 and mortality cohort (p = 0.002). Respiratory rate showed rhythmicity in the recovery cohort (p<0.001), but not in the other cohorts (p = 0.18 and p = 0.51). Skin temperature also showed rhythmicity in the recovery cohort (p<0.001), but not in the other cohorts (p = 0.22 and p = 0.12). For respiratory insufficiency, only the amplitude of heart rate circadian pattern increased slightly the day before (1.2 (99%CI 0.16-2.2, p = 0.002)). In the mortality cohort, the amplitude of heart rate decreased (-1.5 (99%CI -2.6- -0.42, p<0.001)) and respiratory rate amplitude increased (0.72 (99%CI 0.27-1.3, p = 0.002) the days before death. CONCLUSION: A circadian rhythm is present in heart rate of COVID-19 patients admitted to the general ward. For respiratory rate and skin temperature, rhythmicity was only found in patients who recover, but not in patients developing respiratory insufficiency or death. We found no consistent changes in circadian rhythm amplitude accompanying patient deterioration.

Impact of COVID-19 on ambulatory blood pressure in young adults: a cross-sectional analysis investigating time since diagnosis.

Previous studies have reported detrimental effects of COVID-19 on the peripheral vasculature. However, reports on blood pressure (BP) are inconsistent, and measurements are made only in the laboratory setting. To date, no studies have measured ambulatory BP. In addition, in previous studies, time since COVID-19 diagnosis among participants varied across a wide range, potentially contributing to the inconsistent BP results. Thus, we aimed to perform a comprehensive assessment of BP and BP variability using ambulatory and laboratory (brachial and central) measurements in young adults who had COVID-19. We hypothesized that ambulatory BP would be elevated post-COVID-19 and that measures of BP would be inversely related with time since diagnosis. Twenty-eight young adults who had COVID-19 [11 ± 6 (range 3-22) wk since diagnosis] and 10 controls were studied. Ambulatory daytime, nighttime, and 24-h systolic BP, diastolic BP, and mean BP were not different between the control and COVID groups (e.g., daytime systolic BP: control, 122 ± 12 mmHg; COVID, 122 ± 10 mmHg; P = 0.937). Similar results were observed for laboratory BPs (all P > 0.05). However, ambulatory daytime, nighttime, and 24-h BPs as well as laboratory brachial BPs were inversely correlated with time since COVID-19 diagnosis (e.g., daytime systolic BP: r = -0.444; P = 0.044, nighttime systolic BP: r = -0.518; P = 0.016). Ambulatory and laboratory-measured BP variability were not different between groups nor correlated with time since diagnosis. Collectively, these data suggest that adverse effects of COVID-19 on BP in young adults are minimal and likely transient.NEW & NOTEWORTHY We report for the first time that ambulatory daytime, nighttime, and 24-h blood pressure (BP), as well as laboratory BP, were not different between control and COVID participants. However, a significant inverse relationship with time since COVID-19 diagnosis was found (i.e., greater BP with more recent infection). Ambulatory and laboratory BP variability were unaffected and not related with diagnosis time. These findings suggest that COVID-19 may exert only short-lasting effects on BP in young adults.

Circadian misalignment is associated with Covid-19 infection.

BACKGROUND: Circadian system contributes to the regulation of inflammatory processes, but the role of circadian misalignment as a risk factor for contracting Covid-19 has up to now been poorly studied. The aim of this study was to explore the relationship between circadian misalignment (chronic disturbance of the circadian system) and the risk of Covid-19 infection in a population of subjects suspected of contact or infection with SARS-CoV-2. METHODS: Cross-sectional single-center study conducted during a period without lockdown in winter 2021. Recruitment took place in a Covid-19 outpatient testing center. Subjects between 18 and 45 years old were included whether they were symptomatic or not, healthcare workers or not, in contact with a Covid-19 case or not. To determine social jetlag, a proxy of circadian misalignment, they were asked about their usual sleep-wake behaviors. Usual sleep duration and sleep-wake timing were explored on workdays and free days. Social jetlag was defined as at least 2 h shift of circadian alignment (defined as the difference between mid-sleep on workdays and mid-sleep on free days, mid-sleep as the median between bedtime and rise time). RESULTS: One thousand fourteen subjects were included (sampling rate: 10.8%, 39% men, mean age 28 ± 8) with 56 subjects positive for Covid-19 (positivity rate: 5.5%). Usual mean sleep duration was equivalent in both groups (7h47 versus 7h49, p = 0.733). Social jetlag greater than 2 h comprised 33.3% of subjects in the Covid-19 group versus 20.6% in the control group (p = 0.026). After adjustment on age, gender, BMI and work schedules, subjects presenting with social jetlag greater than 2 h had a 2.07-fold higher likelihood to test positive than subjects who had identical sleep-wake timing on workdays and free days (OR = 2.07, 95%CI = [1.12-3.80], p = 0.024). CONCLUSION: Circadian misalignment not only is present in subjects infected by Covid-19 but could also be responsible for a higher likelihood of being infected. The chronobiological impact on the immune system or a higher likelihood of being exposed to social contacts during nocturnal activities could explain our findings, which need to be confirmed in a future large cohort study. Regular sleep-wake timing could ultimately become a target for preventing Covid-19 infection.

Face Validity of Observed Meal Patterns Reported with 7-Day Diet Diaries in a Large Population-Based Cohort Using Diurnal Variation in Concentration Biomarkers of Dietary Intake.

In a cross-sectional analysis of a population-based cohort (United Kingdom, N = 21,318, 1993-1998), we studied how associations between meal patterns and non-fasting triglyceride and glucose concentrations were influenced by the hour of day at which the blood sample was collected to ascertain face validity of reported meal patterns, as well as the influence of reporting bias (assessed using formula of energy expenditure) on this association. Meal size (i.e., reported energy content), mealtime and meal frequency were reported using pre-structured 7-day diet diaries. In ANCOVA, sex-specific means of biomarker concentrations were calculated by hour of blood sample collection for quartiles of reported energy intake at breakfast, lunch and dinner (meal size). Significant interactions were observed between breakfast size, sampling time and triglyceride concentrations and between lunch size, sampling time and triglyceride, as well as glucose concentrations. Those skipping breakfast had the lowest triglyceride concentrations in the morning and those skipping lunch had the lowest triglyceride and glucose concentrations in the afternoon, especially among acceptable energy reporters. Eating and drinking occasion frequency was weakly associated with glucose concentrations in women and positively associated with triglyceride concentrations in both sexes; stronger associations were observed for larger vs. smaller meals and among acceptable energy reporters. Associations between meal patterns and concentration biomarkers can be observed when accounting for diurnal variation and underreporting. These findings support the use of 7-day diet diaries for studying associations between meal patterns and health.

Use of Physiological Data From a Wearable Device to Identify SARS-CoV-2 Infection and Symptoms and Predict COVID-19 Diagnosis: Observational Study.

BACKGROUND: Changes in autonomic nervous system function, characterized by heart rate variability (HRV), have been associated with infection and observed prior to its clinical identification. OBJECTIVE: We performed an evaluation of HRV collected by a wearable device to identify and predict COVID-19 and its related symptoms. METHODS: Health care workers in the Mount Sinai Health System were prospectively followed in an ongoing observational study using the custom Warrior Watch Study app, which was downloaded to their smartphones. Participants wore an Apple Watch for the duration of the study, measuring HRV throughout the follow-up period. Surveys assessing infection and symptom-related questions were obtained daily. RESULTS: Using a mixed-effect cosinor model, the mean amplitude of the circadian pattern of the standard deviation of the interbeat interval of normal sinus beats (SDNN), an HRV metric, differed between subjects with and without COVID-19 (P=.006). The mean amplitude of this circadian pattern differed between individuals during the 7 days before and the 7 days after a COVID-19 diagnosis compared to this metric during uninfected time periods (P=.01). Significant changes in the mean and amplitude of the circadian pattern of the SDNN was observed between the first day of reporting a COVID-19-related symptom compared to all other symptom-free days (P=.01). CONCLUSIONS: Longitudinally collected HRV metrics from a commonly worn commercial wearable device (Apple Watch) can predict the diagnosis of COVID-19 and identify COVID-19-related symptoms. Prior to the diagnosis of COVID-19 by nasal swab polymerase chain reaction testing, significant changes in HRV were observed, demonstrating the predictive ability of this metric to identify COVID-19 infection.

Circadian disruption and human health.

Circadian disruption is pervasive and can occur at multiple organizational levels, contributing to poor health outcomes at individual and population levels. Evidence points to a bidirectional relationship, in that circadian disruption increases disease severity and many diseases can disrupt circadian rhythms. Importantly, circadian disruption can increase the risk for the expression and development of neurologic, psychiatric, cardiometabolic, and immune disorders. Thus, harnessing the rich findings from preclinical and translational research in circadian biology to enhance health via circadian-based approaches represents a unique opportunity for personalized/precision medicine and overall societal well-being. In this Review, we discuss the implications of circadian disruption for human health using a bench-to-bedside approach. Evidence from preclinical and translational science is applied to a clinical and population-based approach. Given the broad implications of circadian regulation for human health, this Review focuses its discussion on selected examples in neurologic, psychiatric, metabolic, cardiovascular, allergic, and immunologic disorders that highlight the interrelatedness between circadian disruption and human disease and the potential of circadian-based interventions, such as bright light therapy and exogenous melatonin, as well as chronotherapy to improve and/or modify disease outcomes.

Outdoor daylight exposure and longer sleep promote wellbeing under COVID-19 mandated restrictions.

Light is an important regulator of daily human physiology in providing time-of-day information for the circadian clock to stay synchronised with the 24-hr day. The coronavirus disease 2019 (COVID-19) pandemic led to social restrictions in many countries to prevent virus spreading, restrictions that dramatically altered daily routines and limited outdoor daylight exposure. We previously reported that sleep duration increased, social jetlag decreased, and mid-sleep times delayed during social restrictions (Global Chrono Corona Survey, N = 7,517). In the present study, we investigated in the same dataset changes in wellbeing and their link to outdoor daylight exposure, and sleep-wake behaviour. In social restrictions, median values of sleep quality, quality of life, physical activity and productivity deteriorated, while screen time increased, and outdoor daylight exposure was reduced by ~58%. Yet, many survey participants also reported no changes or even improvements. Larger reductions in outdoor daylight exposure were linked to deteriorations in wellbeing and delayed mid-sleep times. Notably, sleep duration was not associated with outdoor daylight exposure loss. Longer sleep and decreased alarm-clock use dose-dependently correlated with changes in sleep quality and quality of life. Regression analysis for each wellbeing aspect showed that a model with six predictors including both levels and their deltas of outdoor daylight exposure, sleep duration and mid-sleep timing explained 5%-10% of the variance in changes of wellbeing scores (except for productivity). As exposure to daylight may extenuate the negative effects of social restriction and prevent sleep disruption, public strategies during pandemics should actively foster spending more daytime outdoors.

Demographic, psychological, chronobiological, and work-related predictors of sleep disturbances during the COVID-19 lockdown in Italy.

The first COVID-19 contagion wave caused unprecedented restraining measures worldwide. In Italy, a period of generalized lockdown involving home confinement of the entire population was imposed for almost two months (9 March-3 May 2020). The present is the most extensive investigation aimed to unravel the demographic, psychological, chronobiological, and work-related predictors of sleep disturbances throughout the pandemic emergency. A total of 13,989 Italians completed a web-based survey during the confinement period (25 March-3 May). We collected demographic and lockdown-related work changes information, and we evaluated sleep quality, insomnia and depression symptoms, chronotype, perceived stress, and anxiety using validated questionnaires. The majority of the respondents reported a negative impact of confinement on their sleep and a delayed sleep phase. We highlighted an alarming prevalence of sleep disturbances during the lockdown. Main predictors of sleep disturbances identified by regression models were: female gender, advanced age, being a healthcare worker, living in southern Italy, confinement duration, and a higher level of depression, stress, and anxiety. The evening chronotype emerged as a vulnerability factor, while morning-type individuals showed a lower predisposition to sleep and psychological problems. Finally, working from home was associated with less severe sleep disturbances. Besides confirming the role of specific demographic and psychological factors in developing sleep disorders during the COVID-19 pandemic, we propose that circadian typologies could react differently to a particular period of reduced social jetlag. Moreover, our results suggest that working from home could play a protective role against the development of sleep disturbances during the current pandemic emergency.

Effects of societal-level COVID-19 mitigation measures on the timing and quality of sleep in Ireland.

OBJECTIVES: Under usual circumstances, sleep timing is strongly influenced by societal imperatives. The sweeping whole-of-society measures introduced in response to the COVID-19 pandemic may represent a unique opportunity to examine the impact of large-scale changes in work practices on sleep timing. As such, we examined the impact of the travel restrictions and work from home orders imposed in Ireland in March 2020 on sleep timing and quality. METHODS: We utilized a cross-sectional survey deployed shortly after the imposition of restrictions which assessed current and retrospective ratings of sleep timing and quality; the final response set analysed was from 797 adults. Participants completed the ultra-short Munich Chronotype Questionnaire, the Pittsburg Sleep Quality Index, and answered questions pertaining to work status such as working from home during the period of restrictions. RESULTS AND CONCLUSION: There was a significant shift to later sleep start and end times, as well as delayed time of midsleep on both work and free days, during the period of restrictions. Sleep duration was longer for work days, while free day sleep duration was shorter and there was a reduction in social jetlag during the restrictions. Those who worked from home during restrictions had longer sleep duration on work day and had a significantly larger difference in sleep end on work day than "essential" workers who continued to attend their normal place of work.

A Timely Call to Arms: COVID-19, the Circadian Clock, and Critical Care.

We currently find ourselves in the midst of a global coronavirus disease 2019 (COVID-19) pandemic, caused by the highly infectious novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we discuss aspects of SARS-CoV-2 biology and pathology and how these might interact with the circadian clock of the host. We further focus on the severe manifestation of the illness, leading to hospitalization in an intensive care unit. The most common severe complications of COVID-19 relate to clock-regulated human physiology. We speculate on how the pandemic might be used to gain insights on the circadian clock but, more importantly, on how knowledge of the circadian clock might be used to mitigate the disease expression and the clinical course of COVID-19.

Drivers of Infectious Disease Seasonality: Potential Implications for COVID-19.

Not 1 year has passed since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). Since its emergence, great uncertainty has surrounded the potential for COVID-19 to establish as a seasonally recurrent disease. Many infectious diseases, including endemic human coronaviruses, vary across the year. They show a wide range of seasonal waveforms, timing (phase), and amplitudes, which differ depending on the geographical region. Drivers of such patterns are predominantly studied from an epidemiological perspective with a focus on weather and behavior, but complementary insights emerge from physiological studies of seasonality in animals, including humans. Thus, we take a multidisciplinary approach to integrate knowledge from usually distinct fields. First, we review epidemiological evidence of environmental and behavioral drivers of infectious disease seasonality. Subsequently, we take a chronobiological perspective and discuss within-host changes that may affect susceptibility, morbidity, and mortality from infectious diseases. Based on photoperiodic, circannual, and comparative human data, we not only identify promising future avenues but also highlight the need for further studies in animal models. Our preliminary assessment is that host immune seasonality warrants evaluation alongside weather and human behavior as factors that may contribute to COVID-19 seasonality, and that the relative importance of these drivers requires further investigation. A major challenge to predicting seasonality of infectious diseases are rapid, human-induced changes in the hitherto predictable seasonality of our planet, whose influence we review in a final outlook section. We conclude that a proactive multidisciplinary approach is warranted to predict, mitigate, and prevent seasonal infectious diseases in our complex, changing human-earth system.