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  • Hoever, P., et al. (author)
  • Orexin Receptor Antagonism, a New Sleep-Enabling Paradigm: A Proof-of-Concept Clinical Trial
  • 2012
  • In: Clinical pharmacology and therapeutics. - : Springer Science and Business Media LLC. - 1532-6535 .- 0009-9236. ; 91:6, s. 975-985
  • Journal article (peer-reviewed)abstract
    • The orexin system is a key regulator of sleep and wakefulness. In a multicenter, double-blind, randomized, placebo-controlled, two-way crossover study, 161 primary insomnia patients received either the dual orexin receptor antagonist almorexant, at 400, 200, 100, or 50 mg in consecutive stages, or placebo on treatment nights at 1-week intervals. The primary end point was sleep efficiency (SE) measured by polysomnography; secondary end points were objective latency to persistent sleep (LPS), wake after sleep onset (WASO), safety, and tolerability. Dose-dependent almorexant effects were observed on SE, LPS, and WASO. SE improved significantly after almorexant 400 mg vs. placebo (mean treatment effect 14.4%; P < 0.001). LPS (-18 min (P = 0.02)) and WASO (-54 min (P < 0.001)) decreased significantly at 400 mg vs. placebo. Adverse-event incidence was dose-related. Almorexant consistently and dose-dependently improved sleep variables. The orexin system may offer a new treatment approach for primary insomnia.
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  • Schumann, Gunter, et al. (author)
  • KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference
  • 2016
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:50, s. 14372-14377
  • Journal article (peer-reviewed)abstract
    • Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified beta-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 x 10(-12)). beta-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific beta-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.
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  • Brandao, Luiz Eduardo M., et al. (author)
  • Social Jetlag Changes During the COVID-19 Pandemic as a Predictor of Insomnia - A Multi-National Survey Study
  • 2021
  • In: Nature and Science of Sleep. - : Dove Medical Press. - 1179-1608. ; 13, s. 1711-1722
  • Journal article (peer-reviewed)abstract
    • Purpose: Lifestyle and work habits have been drastically altered by restrictions due to the COVID-19 pandemic. Whether the associated changes in sleep timing modulate the risk of suffering from symptoms of insomnia, the most prevalent sleep disorder, is however incompletely understood. Here, we evaluate the association between the early pandemic-associated change in 1) the magnitude of social jetlag (SJL) - ie, the difference between sleep timing on working vs free days - and 2) symptoms of insomnia.Patients and Methods: A total of 14,968 anonymous participants (mean age: 40 years; 64% females) responded to a standardized internet-based survey distributed across 14 countries. Using logistic multivariate regression, we examined the association between the degree of social jetlag and symptoms of insomnia, controlling for important confounders like social restriction extension, country specific COVID-19 severity and psychological distress, for example.Results: In response to the pandemic, participants reported later sleep timing, especially during workdays. Most participants (46%) exhibited a reduction in their SJL, whereas 20% increased it; and 34% reported no change in SJL. Notably, we found that both increased and decreased SJL, as a result of the COVID-19 pandemic, were associated with later sleep midpoint (indicating a later chronotype) as well as more recurrent and moderate-to-severe symptoms of insomnia (about 23-54% higher odds ratio than subjects with unchanged SJL). Primarily those with reduced SJL shifted their bedtimes to a later timepoint, compared with those without changes in SJL.Conclusion: Our findings offer important insights into how self-reported changes to the stability of sleep/wake timing, as reflected by changes in SJL, can be a critical marker of the risk of experiencing insomnia-related symptoms - even when individuals manage to reduce their social jetlag. These findings emphasize the clinical importance of analyzing sleep-wake regularity.
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  • Dauvilliers, Y., et al. (author)
  • Pitolisant for Daytime Sleepiness in Patients with Obstructive Sleep Apnea Who Refuse Continuous Positive Airway Pressure Treatment A Randomized Trial
  • 2020
  • In: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 201:9, s. 1135-1145
  • Journal article (peer-reviewed)abstract
    • Rationale: Excessive daytime sleepiness is a common disabling symptom in obstructive sleep apnea syndrome. Objectives: To evaluate the efficacy and safety of pitolisant, a selective histamine H3 receptor antagonist with wake-promoting effects, for the treatment of daytime sleepiness in patients with moderate to severe obstructive sleep apnea refusing continuous positive airway pressure treatment. Methods: In an international, multicenter, double-blind, randomized (3:1), placebo-controlled, parallel-design trial, pitolisant was individually titrated at up to 20 mgld over 12 weeks. The primary endpoint was the change in the Epworth Sleepiness Scale score. Key secondary endpoints were maintenance of wakefulness assessed on the basis of the Oxford Sleep Resistance test, safety, Clinical Global Impression of severity, patient's global opinion, EuroQol quality-of-life questionnaire, and Pichot fatigue questionnaire. Measurements and Main Results: A total of 268 patients with obstructive sleep apnea (75% male; mean age, 52 yr; apnea-hypopnea index, 49/h; baseline sleepiness score, 15.7) were randomized (200 to pitolisant and 68 to placebo) and analyzed on an intention-to-treat basis. The Epworth Sleepiness Scale score was reduced more with pitolisant than with placebo (-2.8; 95% confidence interval, -4.0 to -1.5; P < 0.001). Wake maintenance tests were not improved. The Pichot fatigue score was reduced with pitolisant. The overall impact of pitolisant was confirmed by both physicians' and patients' questionnaires. Adverse event incidence, mainly headache, insomnia, nausea, and vertigo, was similar in the pitolisant and placebo groups (29.5% and 25.4%, respectively), with no cardiovascular or other significant safety concerns. Conclusions: Pitolisant significantly reduced self-reported daytime sleepiness and fatigue and improved patient-reported outcomes and physician disease severity assessment in sleepy patients with obstructive sleep apnea refusing or nonadherent to continuous positive airway pressure.
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  • Ollila, Hanna M., et al. (author)
  • Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy
  • 2023
  • In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
  • Journal article (peer-reviewed)abstract
    • Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix (R). Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix (R).
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  • Thebault, S., et al. (author)
  • Neuronal Antibodies in Children with or without Narcolepsy following H1N1-AS03 Vaccination
  • 2015
  • In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:6
  • Journal article (peer-reviewed)abstract
    • Type 1 narcolepsy is caused by deficiency of hypothalamic orexin/hypocretin. An autoimmune basis is suspected, but no specific antibodies, either causative or as biomarkers, have been identified. However, the AS03 adjuvanted split virion H1N1 (H1N1-AS03) vaccine, created to protect against the 2009 Pandemic, has been implicated as a trigger of narcolepsy particularly in children. Sera and CSFs from 13 H1N1-AS03-vaccinated patients (12 children, 1 young adult) with type 1 narcolepsy were tested for autoantibodies to known neuronal antigens including the N-methyl-D-aspartate receptor (NMDAR) and contactin-associated protein 2 (CASPR2), both associated with encephalopathies that include disordered sleep, to rodent brain tissue including the lateral hypothalamus, and to live hippocampal neurons in culture. When sufficient sample was available, CSF levels of melanin-concentrating hormone (MCH) were measured. Sera from 44 H1N1-ASO3-vaccinated children without narcolepsy were also examined. None of these patients' CSFs or sera was positive for NMDAR or CASPR2 antibodies or binding to neurons; 4/13 sera bound to orexin-neurons in rat brain tissue, but also to other neurons. MCH levels were a marginally raised (n = 8; p = 0.054) in orexin-deficient narcolepsy patients compared with orexin-normal children (n = 6). In the 44 H1N1-AS03-vaccinated healthy children, there was no rise in total IgG levels or in CASPR2 or NMDAR antibodies three weeks following vaccination. In conclusion, there were no narcolepsy-specific autoantibodies identified in type 1 narcolepsy sera or CSFs, and no evidence for a general increase in immune reactivity following H1N1-AS03 vaccination in the healthy children. Antibodies to other neuronal specific membrane targets, with their potential for directing use of immunotherapies, are still an important goal for future research.
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  • Berezin, Linor, et al. (author)
  • Habitual short sleepers with pre-existing medical conditions are at higher risk of Long COVID
  • 2024
  • In: Journal of Clinical Sleep Medicine (JCSM). - : American Academy of Sleep Medicine. - 1550-9389 .- 1550-9397. ; 20:1, s. 111-119
  • Journal article (peer-reviewed)abstract
    • STUDY OBJECTIVES: Preliminary evidence suggests that the risk of Long COVID is higher among people with pre-existing medical conditions. Based on its proven adjuvant role in immunity, habitual sleep duration may alter the risk for developing Long COVID. The objective of this study was to determine whether the odds of Long COVID are higher amongst those with pre-existing medical conditions, and whether the strength of this association varies by habitual sleep duration.METHODS: Using data from 13,461 respondents from 16 countries who participated in the 2021 survey based International COVID Sleep Study II (ICOSS II), we studied the associations between habitual sleep duration, pre-existing medical conditions, and Long COVID.RESULTS: Of 2,508 individuals who had COVID-19, 61% reported at least one Long COVID symptom. Multivariable logistic regression analysis showed that the risk of having Long COVID was 1.8-fold higher for average-length sleepers (6-9h/night) with pre-existing medical conditions compared to those without pre-existing medical conditions [aOR 1.84 (1.18-2.90), P=0.008]. The risk of Long COVID was 3-fold higher for short sleepers with pre-existing medical conditions [aOR 2.95 (1.04-8.4), P=0.043] and not significantly higher for long sleepers with pre-existing conditions [aOR 2.11 (0.93-4.77), P=0.073] compared to average-length sleepers without pre-existing conditions.CONCLUSIONS: Habitual short nighttime sleep duration exacerbated the risk of Long COVID in individuals with pre-existing conditions. Restoring nighttime sleep to average duration represents a potentially modifiable behavioral factor to lower the odds of Long COVID for at-risk patients.
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  • Bjorvatn, Bjørn, et al. (author)
  • Shift workers are at increased risk of severe COVID-19 compared with day workers : Results from the international COVID sleep study (ICOSS) of 7141 workers.
  • 2023
  • In: Chronobiology International. - : Taylor & Francis. - 0742-0528 .- 1525-6073. ; 40:2, s. 114-122
  • Journal article (peer-reviewed)abstract
    • The present study had two main aims. First, to investigate whether shift/night workers had a higher prevalence and severity of COVID-19 compared with day workers. Second, to investigate whether people regularly working in face-to-face settings during the pandemic exhibited a higher prevalence and severity of COVID-19 compared with those having no need to be in close contact with others at work. Data consisted of 7141 workers from 15 countries and four continents who participated in the International COVID Sleep Study-II (ICOSS-II) between May and December 2021. The associations between work status and a positive COVID-19 test and several indications of disease severity were tested with chi-square tests and logistic regressions adjusted for relevant confounders. In addition, statistical analyses were conducted for the associations between face-to-face work and COVID-19 status. Results showed that shift/night work was not associated with an increased risk of COVID-19 compared to day work. Still, shift/night workers reported higher odds for moderate to life-threatening COVID-19 (adjusted odds ratio (aOR) = 2.71, 95%-confidence interval = 1.23-5.95) and need for hospital care (aOR = 5.66, 1.89-16.95). Face-to-face work was associated with an increased risk of COVID-19 (aOR = 1.55, 1.12-2.14) but not with higher disease severity. In conclusion, shift/night work was not associated with an increased risk of COVID-19, but when infected, shift/night workers reported more severe disease. Impaired sleep and circadian disruption commonly seen among shift/night workers may be mediating factors. Working face-to-face increased the risk of COVID-19, likely due to increased exposure to the virus. However, face-to-face work was not associated with increased disease severity.
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  • Bolstad, Courtney J, et al. (author)
  • Nightmare frequency is a risk factor for suicidal ideation during the COVID-19 pandemic.
  • 2024
  • In: Journal of Sleep Research. - : WILEY. - 0962-1105 .- 1365-2869. ; , s. e14165-
  • Journal article (peer-reviewed)abstract
    • The association between nightmare frequency (NMF) and suicidal ideation (SI) is well known, yet the impact of the COVID-19 pandemic on this relation is inconsistent. This study aimed to investigate changes in NMF, SI, and their association during the COVID-19 pandemic. Data were collected in 16 countries using a harmonised questionnaire. The sample included 9328 individuals (4848 women; age M[SD] = 46.85 [17.75] years), and 17.60% reported previous COVID-19. Overall, SI was significantly 2% lower during the pandemic vs. before, and this was consistent across genders and ages. Most countries/regions demonstrated decreases in SI during this pandemic, with Austria (-9.57%), Sweden (-6.18%), and Bulgaria (-5.14%) exhibiting significant declines in SI, but Italy (1.45%) and Portugal (2.45%) demonstrated non-significant increases. Suicidal ideation was more common in participants with long-COVID (21.10%) vs. short-COVID (12.40%), though SI did not vary by COVID-19 history. Nightmare frequency increased by 4.50% during the pandemic and was significantly higher in those with previous COVID-19 (14.50% vs. 10.70%), during infection (23.00% vs. 8.10%), and in those with long-COVID (18.00% vs. 8.50%). The relation between NMF and SI was not significantly stronger during the pandemic than prior (rs = 0.18 vs. 0.14; z = 2.80). Frequent nightmares during the pandemic increased the likelihood of reporting SI (OR = 1.57, 95% CI 1.20-2.05), while frequent dream recall during the pandemic served a protective effect (OR = 0.74, 95% CI 0.59-0.94). These findings have important implications for identifying those at risk of suicide and may offer a potential pathway for suicide prevention.
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  • Chen, Si-Jing, et al. (author)
  • The association of insomnia with long COVID : An international collaborative study (ICOSS-II)
  • 2023
  • In: Sleep Medicine. - : Elsevier. - 1389-9457 .- 1878-5506. ; 112, s. 216-222
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: There is evidence of a strong association between insomnia and COVID-19, yet few studies have examined the relationship between insomnia and long COVID. This study aimed to investigate whether COVID-19 patients with pre-pandemic insomnia have a greater risk of developing long COVID and whether long COVID is in turn associated with higher incident rates of insomnia symptoms after infection.METHODS: Data were collected cross-sectionally (May-Dec 2021) as part of an international collaborative study involving participants from 16 countries. A total of 2311 participants (18-99 years old) with COVID-19 provided valid responses to a web-based survey about sleep, insomnia, and health-related variables. Log-binomial regression was used to assess bidirectional associations between insomnia and long COVID. Analyses were adjusted for age, sex, and health conditions, including sleep apnea, attention and memory problems, chronic fatigue, depression, and anxiety.RESULTS: COVID-19 patients with pre-pandemic insomnia showed a higher risk of developing long COVID than those without pre-pandemic insomnia (70.8% vs 51.4%; adjusted relative risk [RR]: 1.33, 95% confidence interval [CI]: 1.07-1.65). Among COVID-19 cases without pre-pandemic insomnia, the rates of incident insomnia symptoms after infection were 24.1% for short COVID cases and 60.6% for long COVID cases (p < .001). Compared with short COVID cases, long COVID cases were associated with an increased risk of developing insomnia symptoms (adjusted RR: 2.00; 95% CI: 1.50-2.66).CONCLUSIONS: The findings support a bidirectional relationship between insomnia and long COVID. These findings highlight the importance of addressing sleep and insomnia in the prevention and management of long COVID.
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  • Chung, Frances, et al. (author)
  • The association between high risk of sleep apnea, comorbidities, and risk of COVID-19 : a population-based international harmonized study
  • 2021
  • In: Sleep and Breathing. - : Springer Nature. - 1520-9512 .- 1522-1709. ; 25:2, s. 849-860
  • Journal article (peer-reviewed)abstract
    • PURPOSE: Obstructive sleep apnea (OSA) may increase the risk of severe COVID-19; however, the level of potential modulation has not yet been established. The objective of the study was to determine the association between high risk of OSA, comorbidities, and increased risk for COVID-19, hospitalization, and intensive care unit (ICU) treatment.METHODS: We conducted a cross-sectional population-based web survey in adults in 14 countries/regions. The survey included sociodemographic variables and comorbidities. Participants were asked questions about COVID-19, hospitalization, and ICU treatment. Standardized questionnaire (STOP questionnaire for high risk of OSA) was included. Multivariable logistic regression was conducted adjusting for various factors.RESULTS: Out of 26,539 respondents, 20,598 (35.4% male) completed the survey. Mean age and BMI of participants were 41.5 ± 16.0 years and 24.0 ± 5.0 kg/m2, respectively. The prevalence of physician-diagnosed OSA was 4.1% and high risk of OSA was 9.5%. We found that high risk of OSA (adjusted odds ratio (aOR) 1.72, 95% confidence interval (CI): 1.20, 2.47) and diabetes (aOR 2.07, 95% CI: 1.23, 3.48) were associated with reporting of a COVID-19 diagnosis. High risk for OSA (aOR 2.11, 95% CI: 1.10-4.01), being male (aOR: 2.82, 95% CI: 1.55-5.12), having diabetes (aOR: 3.93, 95% CI: 1.70-9.12), and having depression (aOR: 2.33, 95% CI: 1.15-4.77) were associated with increased risk of hospitalization or ICU treatment.CONCLUSIONS: Participants at high risk of OSA had increased odds of having COVID-19 and were two times more likely to be hospitalized or treated in ICU.
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  • Häggmark-Månberg, Anna, et al. (author)
  • Autoantibody targets in vaccine-associated narcolepsy
  • 2016
  • In: Autoimmunity. - : Taylor & Francis. - 0891-6934 .- 1607-842X. ; 49:6, s. 421-433
  • Journal article (peer-reviewed)abstract
    • Narcolepsy is a chronic sleep disorder with a yet unknown cause, but the specific loss of hypocretin-producing neurons together with a strong human leukocyte antigen (HLA) association has led to the hypothesis that autoimmune mechanisms might be involved. Here, we describe an extensive effort to profile autoimmunity repertoires in serum with the aim to find disease-related autoantigens. Initially, 57 serum samples from vaccine-associated and sporadic narcolepsy patients and controls were screened for IgG reactivity towards 10 846 fragments of human proteins using planar microarrays. The discovered differential reactivities were verified on suspension bead arrays in the same sample collection followed by further investigation of 14 antigens in 176 independent samples, including 57 narcolepsy patients. Among these 14 antigens, methyltransferase-like 22 (METTL22) and 5'-nucleotidase cytosolic IA (NT5C1A) were recognized at a higher frequency in narcolepsy patients of both sample sets. Upon sequence analysis of the 14 proteins, polymerase family, member 3 (PARP3), acyl-CoA-binding domain containing 7 (ARID4B), glutaminase 2 (GLS2) and cyclin-dependent kinase-like 1 (CDKL1) were found to contain amino acid sequences with homology to proteins found in the H1N1 vaccine. These findings could become useful elements of further clinical assays that aim towards a better phenotypic understanding of narcolepsy and its triggers.
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  • Korman, Maria, et al. (author)
  • Estimation bias and agreement limits between two common self-report methods of habitual sleep duration in epidemiological surveys
  • 2024
  • In: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 14:1
  • Journal article (peer-reviewed)abstract
    • Accurate measurement of habitual sleep duration (HSD) is crucial for understanding the relationship between sleep and health. This study aimed to assess the bias and agreement limits between two commonly used short HSD self-report methods, considering sleep quality (SQ) and social jetlag (SJL) as potential predictors of bias. Data from 10,268 participants in the International COVID Sleep Study-II (ICOSS-II) were used. Method-Self and Method-MCTQ were compared. Method-Self involved a single question about average nightly sleep duration (HSDself), while Method-MCTQ estimated HSD from reported sleep times on workdays (HSDMCTQwork) and free days (HSDMCTQfree). Sleep quality was evaluated using a Likert scale and the Insomnia Severity Index (ISI) to explore its influence on estimation bias. HSDself was on average 42.41 +/- 67.42 min lower than HSDMCTQweek, with an agreement range within +/- 133 min. The bias and agreement range between methods increased with poorer SQ. HSDMCTQwork showed less bias and better agreement with HSDself compared to HSDMCTQfree. Sleep duration irregularity was - 43.35 +/- 78.26 min on average. Subjective sleep quality predicted a significant proportion of variance in HSDself and estimation bias. The two methods showed very poor agreement and a significant systematic bias, both worsening with poorer SQ. Method-MCTQ considered sleep intervals without adjusting for SQ issues such as wakefulness after sleep onset but accounted for sleep irregularity and sleeping in on free days, while Method-Self reflected respondents' interpretation of their sleep, focusing on their sleep on workdays. Including an SQ-related question in surveys may help bidirectionally adjust the possible bias and enhance the accuracy of sleep-health studies.
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  • Matsui, Kentaro, et al. (author)
  • Associations between changes in habitual sleep duration and lower self-rated health among COVID-19 survivors : findings from a survey across 16 countries/regions
  • 2023
  • In: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 23:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Self-rated health (SRH) is widely recognized as a clinically significant predictor of subsequent mortality risk. Although COVID-19 may impair SRH, this relationship has not been extensively examined. The present study aimed to examine the correlation between habitual sleep duration, changes in sleep duration after infection, and SRH in subjects who have experienced SARS-CoV-2 infection.METHODS: Participants from 16 countries participated in the International COVID Sleep Study-II (ICOSS-II) online survey in 2021. A total of 10,794 of these participants were included in the analysis, including 1,509 COVID-19 individuals (who reported that they had tested positive for COVID-19). SRH was evaluated using a 0-100 linear visual analog scale. Habitual sleep durations of < 6 h and > 9 h were defined as short and long habitual sleep duration, respectively. Changes in habitual sleep duration after infection of ≤ -2 h and ≥ 1 h were defined as decreased or increased, respectively.RESULTS: Participants with COVID-19 had lower SRH scores than non-infected participants, and those with more severe COVID-19 had a tendency towards even lower SRH scores. In a multivariate regression analysis of participants who had experienced COVID-19, both decreased and increased habitual sleep duration after infection were significantly associated with lower SRH after controlling for sleep quality (β = -0.056 and -0.058, respectively, both p < 0.05); however, associations between current short or long habitual sleep duration and SRH were negligible. Multinomial logistic regression analysis showed that decreased habitual sleep duration was significantly related to increased fatigue (odds ratio [OR] = 1.824, p < 0.01), shortness of breath (OR = 1.725, p < 0.05), diarrhea/nausea/vomiting (OR = 2.636, p < 0.01), and hallucinations (OR = 5.091, p < 0.05), while increased habitual sleep duration was significantly related to increased fatigue (OR = 1.900, p < 0.01).CONCLUSIONS: Changes in habitual sleep duration following SARS-CoV-2 infection were associated with lower SRH. Decreased or increased habitual sleep duration might have a bidirectional relation with post-COVID-19 symptoms. Further research is needed to better understand the mechanisms underlying these relationships for in order to improve SRH in individuals with COVID-19.
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  • Merikanto, Ilona, et al. (author)
  • Evening-types show highest increase of sleep and mental health problems during the COVID-19 pandemic - Multinational study on 19,267 adults.
  • 2021
  • In: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 45:2
  • Journal article (peer-reviewed)abstract
    • STUDY OBJECTIVES: Individual circadian type is a ubiquitous trait defining sleep, with eveningness often associated with poorer sleep and mental health than morningness. However, it is unknown whether COVID-19 pandemic has differentially affected sleep and mental health depending on the circadian type. Here, the differences in sleep and mental health between circadian types are examined globally before and during the COVID-19 pandemic.METHODS: The sample collected between May and August 2020 across 12 countries/regions consisted of 19,267 adults with information on their circadian type. Statistical analyses were performed by using Complex Sample procedures, stratified by country and weighted by the number of inhabitants in the country/area of interest and by the relative number of responders in that country/area.RESULTS: Evening-types had poorer mental health, well-being, and quality of life or health than other circadian types during the pandemic. Sleep-wake schedules were delayed especially on working days, and evening-types reported an increase in sleep duration. Sleep problems increased in all circadian types, but especially among evening-types, moderated by financial suffering and confinement. Intermediate-types were less vulnerable to sleep changes, although morningness protected from most sleep problems. These findings were confirmed after adjusting for age, sex, duration of the confinement or socio-economic status during the pandemic.CONCLUSIONS: These findings indicate an alarming increase in sleep and mental health problems, especially among evening-types as compared to other circadian types during the pandemic.
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  • Morin, Charles M., et al. (author)
  • Insomnia, anxiety, and depression during the COVID-19 pandemic : an international collaborative study
  • 2021
  • In: Sleep Medicine. - : Elsevier. - 1389-9457 .- 1878-5506. ; 87, s. 38-45
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE AND STUDY OBJECTIVE: The COVID-19 pandemic has produced unprecedented changes in social, work, and leisure activities, which all have had major impact on sleep and psychological well-being. This study documented the prevalence of clinical cases of insomnia, anxiety, and depression and selected risk factors (COVID-19, confinement, financial burden, social isolation) during the first wave of the pandemic in 13 countries throughout the world.DESIGN AND PARTICIPANTS: International, multi-center, harmonized survey of 22 330 adults (mean age = 41.9 years old, range 18-95; 65.6% women) from the general population in 13 countries and four continents. Participants were invited to complete a standardized web-based survey about sleep and psychological symptoms during the first wave of the COVID-19 pandemic from May to August 2020.RESULTS: Clinical insomnia symptoms were reported by 36.7% (95% CI, 36.0-37.4) of respondents and 17.4% (95% CI, 16.9-17.9) met criteria for a probable insomnia disorder. There were 25.6% (95% CI, 25.0-26.2) with probable anxiety and 23.1% (95% CI, 22.5-23.6) with probable depression. Rates of insomnia symptoms (>40%) and insomnia disorder (>25%) were significantly higher in women, younger age groups, and in residents of Brazil, Canada, Norway, Poland, USA, and United Kingdom compared to residents from Asian countries (China and Japan, 8% for disorder and 22%-25% for symptoms) (all Ps < 0.01). Proportions of insomnia cases were significantly higher among participants who completed the survey earlier in the first wave of the pandemic relative to those who completed it later. Risks of insomnia were higher among participants who reported having had COVID-19, who reported greater financial burden, were in confinement for a period of four to five weeks, and living alone or with more than five people in same household. These associations remained significant after controlling for age, sex, and psychological symptoms.CONCLUSION AND RELEVANCE: Insomnia, anxiety, and depression were very prevalent during the first wave of the COVID-19 pandemic. Public health prevention programs are needed to prevent chronicity and reduce long-term adverse outcomes associated with chronic insomnia and mental health problems.
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  • Partinen, Markku, et al. (author)
  • Sleep and daytime problems during the COVID-19 pandemic and effects of coronavirus infection, confinement and financial suffering : a multinational survey using a harmonised questionnaire
  • 2021
  • In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:12
  • Journal article (peer-reviewed)abstract
    • Objectives Sleep is important for human health and well-being. No previous study has assessed whether the COVID-19 pandemic impacts sleep and daytime function across the globe. Methods This large-scale international survey used a harmonised questionnaire. Fourteen countries participated during the period of May-August 2020. Sleep and daytime problems (poor sleep quality, sleep onset and maintenance problems, nightmares, hypnotic use, fatigue and excessive sleepiness) occurring 'before' and 'during' the pandemic were investigated. In total, 25 484 people participated and 22 151 (86.9%) responded to the key parameters and were included. Effects of COVID-19, confinement and financial suffering were considered. In the fully adjusted logistic regression models, results (weighted and stratified by country) were adjusted for gender, age, marital status, educational level, ethnicity, presence of sleep problems before COVID-19 and severity of the COVID-19 pandemic in each country at the time of the survey. Results The responders were mostly women (64%) with a mean age 41.8 (SD 15.9) years (median 39, range 18-95). Altogether, 3.0% reported having had COVID-19; 42.2% reported having been in confinement; and 55.9% had suffered financially. All sleep and daytime problems worsened during the pandemic by about 10% or more. Also, some participants reported improvements in sleep and daytime function. For example, sleep quality worsened in about 20% of subjects and improved in about 5%. COVID-19 was particularly associated with poor sleep quality, early morning awakening and daytime sleepiness. Confinement was associated with poor sleep quality, problems falling asleep and decreased use of hypnotics. Financial suffering was associated with all sleep and daytime problems, including nightmares and fatigue, even in the fully adjusted logistic regression models. Conclusions Sleep problems, fatigue and excessive sleepiness increased significantly worldwide during the first phase of the COVID-19 pandemic. Problems were associated with confinement and especially with financial suffering.
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28.
  • Sarkanen, Tomi, et al. (author)
  • Association between hypersomnolence and the COVID-19 pandemic : The International COVID-19 Sleep Study (ICOSS).
  • 2023
  • In: Sleep Medicine. - : Elsevier. - 1389-9457 .- 1878-5506. ; 107, s. 108-115
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The COVID-19 pandemic and related restriction measures have affected our daily life, sleep, and circadian rhythms worldwide. Their effects on hypersomnolence and fatigue remain unclear.METHODS: The International COVID-19 Sleep Study questionnaire which included items on hypersomnolence such as excessive daytime sleepiness (EDS), and excessive quantity of sleep (EQS), as well as sociodemographic factors, sleep patterns, psychological symptoms, and quality of life was distributed in 15 countries across the world from May to September in 2020.RESULTS: Altogether responses from 18,785 survey participants (65% women, median age 39 years) were available for analysis. Only 2.8% reported having had COVID-19. Compared to before the pandemic, the prevalence of EDS, EQS, and fatigue increased from 17.9% to 25.5%, 1.6%-4.9%, and 19.4%-28.3% amid the pandemic, respectively. In univariate logistic regression models, reports of having a COVID-19 were associated with EQS (OR 5.3; 95%-CI 3.6-8.0), EDS (2.6; 2.0-3.4), and fatigue (2.8; 2.1-3.6). In adjusted multivariate logistic regression, sleep duration shorter than desired (3.9; 3.2-4.7), depressive symptoms (3.1; 2.7-3.5), use of hypnotics (2.3; 1.9-2.8), and having reported COVID-19 (1.9; 1.3-2.6) remained strong predictors of EDS. Similar associations emerged for fatigue. In the multivariate model, depressive symptoms (4.1; 3.6-4.6) and reports of having COVID-19 (2.0; 1.4-2.8) remained associated with EQS.CONCLUSIONS: A large increase in EDS, EQS, and fatigue occurred due to the COVID-19 pandemic, and especially in self-reported cases of COVID-19. These findings warrant a thorough understanding of their pathophysiology to target prevention and treatment strategies for long COVID condition.
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29.
  • Xue, Pei, et al. (author)
  • Associations between obesity, a composite risk score for probable long COVID, and sleep problems in SARS-CoV-2 vaccinated individuals.
  • 2024
  • In: International Journal of Obesity. - 0307-0565 .- 1476-5497.
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Preliminary data suggests that obesity might hasten the decline in mRNA vaccine-induced immunity against SARS-CoV-2. However, whether this renders individuals with obesity more susceptible to long COVID symptoms post-vaccination remains uncertain. Given sleep's critical role in immunity, exploring the associations between obesity, probable long COVID symptoms, and sleep disturbances is essential.METHODS: We analyzed data from a survey of 5919 adults aged 18 to 89, all of whom received two SARS-CoV-2 mRNA vaccinations. Participants were categorized into normal weight, overweight, and obesity groups based on ethnicity-specific BMI cutoffs. The probability of long COVID was evaluated using the Post-Acute Sequelae of SARS-CoV-2 (PASC) score, as our survey did not permit confirmation of acute SARS-CoV-2 infection through methods such as antibody testing. Additionally, sleep patterns were assessed through questionnaires.RESULTS: Participants with obesity exhibited a significantly higher adjusted odds ratio (OR) of having a PASC score of 12 or higher, indicative of probable long COVID in our study, compared to those with normal weight (OR: 1.55, 95% CI: 1.05, 2.28). No significant difference was observed for overweight individuals (OR: 0.92 [95% CI: 0.63, 1.33]). Both obesity and probable long COVID were associated with increased odds of experiencing a heightened sleep burden, such as the presence of obstructive sleep apnea or insomnia (P < 0.001). However, no significant interaction between BMI and probable long COVID status was found.CONCLUSIONS: Even post-vaccination, individuals with obesity may encounter a heightened risk of experiencing prolonged COVID-19 symptoms. However, confirming our observations necessitates comprehensive studies incorporating rigorous COVID infection testing, such as antibody assays - unavailable in our anonymous survey. Additionally, it is noteworthy that the correlation between probable long COVID and sleep disturbances appears to be independent of BMI.
  •  
30.
  • Xue, Pei, et al. (author)
  • Associations between obesity, a composite risk score for probable long COVID, and sleep problems in SARS-CoV-2 vaccinated individuals
  • 2024
  • In: International Journal of Obesity. - : SPRINGERNATURE. - 0307-0565 .- 1476-5497.
  • Journal article (peer-reviewed)abstract
    • Background: Preliminary data suggests that obesity might hasten the decline in mRNA vaccine-induced immunity against SARS-CoV-2. However, whether this renders individuals with obesity more susceptible to long COVID symptoms post-vaccination remains uncertain. Given sleep's critical role in immunity, exploring the associations between obesity, probable long COVID symptoms, and sleep disturbances is essential. Methods: We analyzed data from a survey of 5919 adults aged 18 to 89, all of whom received two SARS-CoV-2 mRNA vaccinations. Participants were categorized into normal weight, overweight, and obesity groups based on ethnicity-specific BMI cutoffs. The probability of long COVID was evaluated using the Post-Acute Sequelae of SARS-CoV-2 (PASC) score, as our survey did not permit confirmation of acute SARS-CoV-2 infection through methods such as antibody testing. Additionally, sleep patterns were assessed through questionnaires. Results: Participants with obesity exhibited a significantly higher adjusted odds ratio (OR) of having a PASC score of 12 or higher, indicative of probable long COVID in our study, compared to those with normal weight (OR: 1.55, 95% CI: 1.05, 2.28). No significant difference was observed for overweight individuals (OR: 0.92 [95% CI: 0.63, 1.33]). Both obesity and probable long COVID were associated with increased odds of experiencing a heightened sleep burden, such as the presence of obstructive sleep apnea or insomnia (P < 0.001). However, no significant interaction between BMI and probable long COVID status was found. Conclusions: Even post-vaccination, individuals with obesity may encounter a heightened risk of experiencing prolonged COVID-19 symptoms. However, confirming our observations necessitates comprehensive studies incorporating rigorous COVID infection testing, such as antibody assays - unavailable in our anonymous survey. Additionally, it is noteworthy that the correlation between probable long COVID and sleep disturbances appears to be independent of BMI.
  •  
31.
  • Xue, Pei, et al. (author)
  • Persistent short nighttime sleep duration is associated with a greater post-COVID risk in fully mRNA-vaccinated individuals.
  • 2023
  • In: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 13:1, s. 32-
  • Journal article (peer-reviewed)abstract
    • Short nighttime sleep duration impairs the immune response to virus vaccination, and long nighttime sleep duration is associated with poor health status. Thus, we hypothesized that short (<6 h) and long (>9 h) nighttime sleepers have a higher post-COVID risk than normal nighttime sleepers, despite two doses of mRNA vaccine (which has previously been linked to lower odds of long-lasting COVID-19 symptoms). Post-COVID was defined as experiencing at least one core COVID-19 symptom for at least three months (e.g., shortness of breath). Multivariate logistic regression adjusting for age, sex, BMI, and other factors showed in 9717 respondents (age span 18-99) that two mRNA vaccinations lowered the risk of suffering from post-COVID by about 21% (p < 0.001). When restricting the analysis to double-vaccinated respondents (n = 5918), short and long sleepers exhibited a greater post-COVID risk than normal sleepers (adjusted OR [95%-CI], 1.56 [1.29, 1.88] and 1.87 [1.32, 2.66], respectively). Among respondents with persistent sleep duration patterns during the pandemic compared to before the pandemic, short but not long sleep duration was significantly associated with the post-COVID risk (adjusted OR [95%-CI], 1.59 [1.24, 2.03] and 1.18 [0.70, 1.97], respectively). No significant association between sleep duration and post-COVID symptoms was observed in those reporting positive SARS-CoV-2 test results (n = 538). Our findings suggest that two mRNA vaccinations against SARS-CoV-2 are associated with a lower post-COVID risk. However, this protection may be less pronounced among those sleeping less than 6 h per night. Our findings warrant replication in cohorts with individuals with confirmed SARS-CoV-2 infection.
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