key: cord-0861755-xcpck3rc
authors: Liu, Yaping; Partinen, Eemil; Chan, Ngan Yin; Dauvilliers, Yves; Inoue, Yuichi; De Gennaro, Luigi; Plazzi, Giuseppe; Bolstad, Courtney J.; Nadorff, Michael R.; Merikanto, Ilona; Bjorvatn, Bjørn; Han, Fang; Zhang, Bin; Cunha, Ana Suely; Mota‐Rolim, Sérgio; Léger, Damien; Matsui, Kentaro; Espie, Colin A.; Chung, Frances; Morin, Charles M.; Sieminski, Mariusz; Thomas, Penzel; Holzinger, Brigitte; Partinen, Markku; Wing, Yun Kwok
title: Dream‐enactment behaviours during the COVID‐19 pandemic: an international COVID‐19 sleep study
date: 2022-04-26
journal: J Sleep Res
DOI: 10.1111/jsr.13613
sha: f1b899df0557b66d924c757b70917b8a7cea5836
doc_id: 861755
cord_uid: xcpck3rc

There has been increasing concern about the long‐term impact of coronavirus disease 2019 (COVID‐19) as evidenced by anecdotal case reports of acute‐onset parkinsonism and the polysomnographic feature of increased rapid eye movement sleep electromyographic activity. This study aimed to determine the prevalence and correlates of dream‐enactment behaviours, a hallmark of rapid eye movement sleep behaviour disorder, which is a prodrome of α‐synucleinopathy. This online survey was conducted between May and August 2020 in 15 countries/regions targeting adult participants (aged ≥18 years) from the general population with a harmonised structured questionnaire on sleep patterns and disorders, COVID‐19 diagnosis and symptoms. We assessed dream‐enactment behaviours using the Rapid Eye Movement Sleep Behaviour Disorder Single‐Question Screen with an additional question on their frequency. Among 26,539 respondents, 21,870 (82.2%) answered all items that were analysed in this study (mean [SD] age 41.6 [15.8] years; female sex 65.5%). The weighted prevalence of lifetime and weekly dream‐enactment behaviours was 19.4% and 3.1% and were found to be 1.8‐ and 2.9‐times higher in COVID‐19‐positive cases, respectively. Both lifetime and weekly dream‐enactment behaviours were associated with young age, male sex, smoking, alcohol consumption, higher physical activity level, nightmares, COVID‐19 diagnosis, olfactory impairment, obstructive sleep apnea symptoms, mood, and post‐traumatic stress disorder features. Among COVID‐19‐positive cases, weekly dream‐enactment behaviours were positively associated with the severity of COVID‐19. Dream‐enactment behaviours are common among the general population during the COVID‐19 pandemic and further increase among patients with COVID‐19. Further studies are needed to investigate the potential neurodegenerative effect of COVID‐19.

Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a global pandemic and has resulted in >270 million confirmed cases and 5.3 million deaths worldwide up to December 2021 (WHO COVID-19

Dashboard, 2020). The COVID-19 pandemic has extensive direct and indirect adverse effects on mood, sleep, and dreams/nightmares, not only among patients with COVID-19 but also in the general population Fränkl et al., 2021; Morin et al., 2021; Salari et al., 2020) . Evidence from SARS-CoV and Middle East respiratory syndrome CoV revealed a neurotropic nature of the infection (Li, Bai, & Hashikawa, 2020) . Previous findings on long-term consequences of SARS-CoV showed that 40% of the survivors suffered from active psychiatric illness and chronic fatigue syndrome 4 years after the infection (Lam et al., 2009 ). Thus, it is conceivable that the same betacoronavirus clade (SARS-CoV-2) may also associate with neuropsychiatric symptoms/disorders, both during the acute and long COVID-19 (referred to as "long COVID") stages (Boldrini, Canoll, & Klein, 2021; Brundin, Nath, & Beckham, 2020) .

Accumulating evidence indicate that olfactory impairment is a common presenting symptom of COVID-19, affecting up to 80% of the cases (von Bartheld, Hagen, & Butowt, 2020) . Importantly, olfactory impairment is often regarded as a heralding feature of neurodegeneration including Parkinson's disease (PD) (Heinzel et al., 2019) . Interestingly, there has been a few confirmed cases with acute onset of parkinsonism supported by neuroimaging evidence of dopamine dysfunction shortly after SARS-CoV-2 infection (Cohen et al., 2020; Faber et al., 2020; Mendez-Guerrero et al., 2020) . Although it is intriguing that parkinsonism could develop in such an acute manner and with the age-onset of parkinsonism being much younger (35-53 years) than the typical age of onset (Cohen et al., 2020; Faber et al., 2020; Mendez-Guerrero et al., 2020) , these findings forewarn of a possible surge of neurodegeneration, including PD, during the long COVID-19 stage (Brundin et al., 2020) .

Rapid eye movment (REM) sleep behaviour disorder (RBD) is a distinct parasomnia characterised by recurrent dream-enactment behaviours (DEBs) and REM sleep without atonia. RBD is regarded as the most specific precursor of α-synucleinopathies, such as PD, as >90% of patients with RBD will convert to clinically diagnosed α-synucleinopathies within 15 years (Galbiati et al., 2019; Postuma et al., 2019) . Thus, a major consideration is on how the SARS-CoV-2 potentially influences the development of RBD features that has a close relationship with parkinsonism. A recent study found that 36% (four out of 11) of patients with COVID-19 presented with REM sleep without atonia on polysomnographic recording (Heidbreder et al., 2021) , which suggested that SARS-CoV-2 might potentially trigger RBD features.

To the best of our knowledge, there is a lack of epidemiological results of DEBs, which is a hallmark of RBD and their correlates during the COVID-19 pandemic in both the general population and patients with COVID-19. We conducted an international online survey, the International COVID-19 Sleep Study (ICOSS), to investigate the impact of the COVID-19 pandemic on sleep and daily rhythms in adults Fränkl et al., 2021; Merikanto et al., 2021; Morin et al., 2021) . In the present study, we aimed to determine the prevalence and correlates of DEBs during the pandemic.

This was a cross-sectional online survey (ICOSS study) conducted during the COVID-19 pandemic between May and August 2020 with 15 participating countries/regions: Austria, Brazil, Canada, Jilin (China), Finland, France, Germany, Hong Kong (China), Italy, Japan, Norway, Poland, Sweden, UK, and USA. The study protocol related to study objectives, questionnaires included, and study procedures have been published .

The potential participants aged ≥18 years were invited to complete an online survey in their own language via local and national news, social media, and newsletters at universities and hospitals. The survey was completed anonymously. The participants who voluntarily agreed to participate in the survey gave their online consent for the purpose of this study. Each international principal investigator obtained approval or exemption from their local Ethics Committee prior to initiation of the survey.

We used the following items from the ICOSS core questionnaire 1. Demographic characteristics (e.g., age, sex, education level, ethnics) data were collected in structured questions. By collecting smoking data, participants were asked about the frequency ("Never or less than once per month," "Less than once per week," "1-2 days per week," "3-5 days per week," and "Every day or almost daily") of smoking (cigarettes, cigars, cigarillos) or use of snuff tobacco. We dichotomised the answers into "less than weekly" and "weekly use." Drinking of alcohol beverages was defined as participants who drank one or more bottle/can of beer, strong beer, cider, wine, or spirits per week.

Caffeine consumption was defined as participants who drank one or more cup of coffee, tea, cola drinks, or energy drinks per day. Physical activity level was measured by asking participants on how many hours per week they did physically workout. The workout options included walking, jogging/cycling, running, and other (e.g., swimming) with frequencies ranged from "Not at all" to "Altogether 4 h or more per week" for each workout option.

2. A COVID-19 diagnosis confirmed by a "yes" answer to the question, "Have you had COVID-19?" Participants answering "I don't know" (18.2%) were coded as having no self-reported COVID-19 disease. Among those reporting COVID-19, we further surveyed the severity of the disease by allowing respondents to rate the severity of disease ("mild," "moderate," "severe," and "life threatening") and whether they were hospitalised for the disease . As only few participants had "life threatening" COVID-19, we put this category into "severe" group to facilitate the data analysis. We also surveyed the presence of the series of COVID-19 symptoms: chills, cough, excessive sleepiness, fatigue, fever, gastrointestinal symptoms, headache, loss of taste and smell, muscle pain, running nose, shortness of breath, difficulty breathing, and sore throat.

3. The RBD Single-Question Screen (RBD1Q) was employed to assess lifetime DEBs (Postuma et al., 2012) . In detail, respondents were asked, "Have you ever been told, or suspected yourself, that you seem to 'act out your dreams' while asleep (for example, punching, flailing your arms in the air, making running movements, etc.)?" (Postuma et al., 2012) . The sensitivity and specificity were 93.8% and 87.2% respectively when RBD1Q was used in clinical setting to differentiate patients with RBD from controls (Postuma et al., 2012) . Besides the RBD1Q, we also surveyed the frequency of the DEBs symptoms on a 5-point scale: "never or <1/month", "<1/week", "1-2 nights/ week", "3-5 nights/week", and "every night or almost every night." We further dichotomised the frequency into "weekly"

and "non-weekly." This may help to capture recurrent weeks DEBs, which would suggest a higher likelihood of harbouring genuine RBD features. 4. The STOP (Snoring, Tiredness, Observed apnea, high blood Pressure) questionnaire to screen for obstructive sleep apnea (OSA) Chung et al., 2008) .

(PHQ-4) to measure anxiety and depressive symptoms (Kroenke, Spitzer, Williams, & Lowe, 2009 ). 6. A two-item self-report measure to evaluate post-traumatic stress disorder (PTSD) symptoms (Lang et al., 2012) . 7. Sense of smell was assessed by two questions. The first question was "How do you rate your own sense of smell (olfactory sense)?" and the seven responses were set and ranged from "extremely good and sensitive" to "cannot smell almost anything." The second question asked about the sense of smell related to COVID-19. The responses included: "no change," "worse than before infection", "worsened and returned back", "cannot smell almost anything."

We classified the responses "worse than before infection" and "cannot smell almost anything" as olfactory impairment.

8. Physical activity level was assessed by calculating weekly time spent on doing walking, jogging or cycling, running, or others (i.e., swimming).

The options ranged from none to 4 h or more on a 5-point scale.

9. Other questions related to insomnia symptoms, sleep pattern, circadian preferences, and OSA symptoms were reported separately Fränkl et al., 2021; Merikanto et al., 2021;  Morin et al., 2021).

The data of this study are presented as mean ± standard deviation (SD) if they fitted normal distribution or number (%) when appropriate. Cases with missing data were excluded in the analyses. The data were weighted by using the post-stratification weighting method.

The weighting index for age and sex was calculated separately based on the age and sex distribution of the population in each country/ region (World Population Prospects 2019, United Nations, 2021), and then multiplied together to get the weighting index for each participant.

Chi-square tests were employed to test the difference in the prevalence of lifetime DEBs and weekly DEBs among different subgroups. To estimate the prevalence of DEBs across different countries/regions, we conducted further meta-analysis. To explore the correlates for DEBs, binary logistic regression models were fitted with DEBs as the dependent variable and each single factor as independent variables after adjusting for age and sex. As the score for physical activity level was not validated, we put the four items into the Principal Components Analysis to generate one score that represents the level of physical activities. To investigate the association of COVID-19 symptoms with DEBs among COVID-19-positive participants, we used logistic regression models among participants with COVID-19 diagnosis. The odds ratio (OR) and the related 95% T A B L E 1 Demographic characteristics and stratified prevalence of lifetime and weekly dream-enactment behaviours 

We performed sensitivity analysis after excluding data from Brazil for questionnaires (Table S1 ). However, COVID-19 severity was not associated with weekly DEBs.

This large-scale international online survey found that DEBs were quite prevalent in the general population during the COVID-19 pandemic and were associated with factors including male sex, life-style factors, olfactory impairment, depression and anxiety symptoms, OSA symptoms, and PTSD symptoms. In particular, we found that COVID-19 diagnosis was associated with increased prevalence of DEBs.

Moreover, COVID-19-related symptoms including chills, gastrointestinal symptoms, loss of taste and smell, running rose, respiratory symptoms and sore throat were significantly associated with DEBs. As one of the core symptoms of RBD, recurrent DEBs in a large-scale epidemiological study may signify the potential occurrence of idiopathic/ isolated RBD. In this regard, the finding of co-occurrence of olfactory impairment and gastrointestinal symptoms with DEBs in our study replicated some previously known neurodegenerative and epidemiological correlates of idiopathic/isolated RBD in general population studies (Haba-Rubio et al., 2018; Ma et al., 2017; Yao et al., 2018) .

Although our findings of the association of DEBs and COVID-19 were novel, there is a need to investigate the association further, especially with the need for confirmatory polysomnographic studies in future.

When compared to previous studies, the prevalence of DEBs in the general population was strikingly high during the COVID-19 pandemic. With various assessment tools, several previous epidemiological studies have revealed that the prevalence of DEBs in the general population ranged from 2.7% to 18.4% (Haba-Rubio et al., 2018; Ma et al., 2017) . Compared to studies that have employed the identical screening questionnaire as in our survey, the prevalence of DEBs in the present ICOSS survey was almost 2-4-times higher than that of previous studies (ranged from 4.9% (Yao et al., 2018) to 9.9% (Shprecher et al., 2020) in previous research).

Several explanations may address the high prevalence of DEBs among the general population during the COVID-19 pandemic. Firstly, a high proportion of these screened-positive cases may likely turn out to be false-positive cases for RBD (pseudo-RBD), as the apparent DEB features might be mimicked by OSA (Iranzo & Santamaria, 2005) , and the risk of OSA was found to be increased during the COVID-19

pandemic . Additionally, other parasomnias and sleep-related movement disorders, such as nightmare disorder and periodic limb movement disorder, may be mis-recognised as RBD symptoms, as these sleep disorders are difficult to differentiate from RBD by the screening question (Bjorvatn, Gronli, & Pallesen, 2010) .

We noted that the global population was suffering from a relatively high level of anxiety, depression, and PTSD symptoms during the COVID-19 pandemic (Morin et al., 2021; Salari et al., 2020) , which might have been associated with an abundance of distress that may culminate into the development of parasomnia (Barone, 2020) . Previous studies suggested that parasomnia including RBD is common among the psychiatric population (Lam, Fong, Ho, Yu, & Wing, 2008; Wang et al., 2021) . Traumatic events and PTSD have been reported to increase the odds of RBD (Elliott et al., 2020) and a global pandemic could be considered as a such. Additionally, several epidemiological studies found that PTSD was associated with DEBs in the general population (Ma et al., 2017; Yao et al., 2018) . In fact, a transient form of RBD has been proposed to be related to a series of acute conditions including central nervous system diseases (e.g., encephalitis), drug consumption or alcohol withdrawal, and also possibly PTSD (Manni, Ratti, & Terzaghi, 2011) .

A rather unexpected finding of the association of DEB with younger age is in contrast to the finding that increasing age is a risk factor for RBD . In other words, there will be a distinct possibility that this young age group may suffer from DEB-like episodes related to non-REM (NREM) parasomnia during the COVID-19

pandemic. In a series of 43 patients with sleepwalking and sleep terrors at a mean age of 26 years, short unpleasant dream-like mentations could occur during NREM parasomnia (Oudiette et al., 2009 ). In addition, almost two-thirds (62.8%) of patients reported at least one incidence of recalling mental content during the episode. Thus, in our present study, dream-like mentations during NREM episodes may have been misclassified as DEBs as based on a single-question screen assessment. Uguccioni et al. (2013) also postulated that different threat simulations may contribute to different types of parasomnia (i.e., natural disaster for NREM parasomnia versus human or animal aggression for REM parasomnia). It is possible that the catastrophic nature of the COVID-19 pandemic might enhance the distress and sleep disruption that will contribute to the dream-like mentation in the NREM parasomnia of young subjects. (Uguccioni et al., 2013; Merikanto et al., 2021; Morin et al., 2021) .

Interestingly, DEBs were associated with a higher level of physical activity in our study. The lockdown or restriction during pandemic may potentially alter the physical activity pattern of participants and the possibility of reverse causality could not be excluded (Bu, Bone, Mitchell, Steptoe, & Fancourt, 2021) . Nonetheless, most of the factors associated with DEBs of the present ICOSS study were consistent with previous general population studies, including male sex (Yao et al., 2018) , smoking (Shrestha et al., 2018; Yao et al., 2018) , alcohol consumption (Ma et al., 2017; Shprecher et al., 2020; Yao et al., 2018) , olfactory impairment (Ma et al., 2017; Shprecher, Zhang, Halverson, & Savica, 2019; Shrestha et al., 2018) , and mood and PTSD symptoms (Ma et al., 2017; Mahlknecht et al., 2015; Yao et al., 2018; Wang et al., 2021) .

It is also worth noting that DEBs can be associated with narcolepsy, a sleep disorder characterised by excessive daytime sleepiness and which increased following the 2009 H1N1 flu pandemic (Han et al., 2011) .

Whether COVID-19 and related vaccines will increase the incidence of narcolepsy remains unknown and deserves further investigation. 

Yaping Liu and Eemil Partinen conducted data analysis and drafted the manuscript. All authors conceptualised and conducted the study, collected the data, and critically revised the manuscript.

The data supporting the findings of this international survey may be requested from the ICOSS group, via the corresponding authors.

https://orcid.org/0000-0002-2015-8775

Luigi De Gennaro https://orcid.org/0000-0003-3613-6631

Dream enactment behavior-a real nightmare: A review of post-traumatic stress disorder, REM sleep behavior disorder, and trauma-associated sleep disorder

Prevalence of different parasomnias in the general population

How COVID-19 affects the brain

Is COVID-19 a perfect storm for Parkinson's Disease?

Longitudinal changes in physical activity during and after the first national lockdown due to the COVID-19 pandemic in England

The association between high risk of sleep apnea, comorbidities, and risk of COVID-19: A population-based international harmonized study

STOP questionnaire: A tool to screen patients for obstructive sleep apnea

A case of probable Parkinson's disease after SARS-CoV-2 infection

Posttraumatic stress disorder increases the odds of REM sleep behavior disorder and other parasomnias in veterans with and without comorbid traumatic brain injury

Coronavirus Disease 2019 and parkinsonism: A non-post-encephalitic case

How our dreams changed during the COVID-19 pandemic: Effects and correlates of dream recall frequency -a multinational study on 19,355 adults

The risk of neurodegeneration in REM sleep behavior disorder: A systematic review and meta-analysis of longitudinal studies

Prevalence and determinants of rapid eye movement sleep behavior disorder in the general population

Narcolepsy onset is seasonal and increased following the 2009 H1N1 pandemic in China

Video-polysomnographic findings after acute COVID-19: REM sleep without atonia as sign of CNS pathology?

Update of the MDS research criteria for prodromal Parkinson's disease. Movement Disorders

Severe obstructive sleep apnea/hypopnea mimicking REM sleep behavior disorder

An ultra-brief screening scale for anxiety and depression: The PHQ-4. Psychosomatics

Mental morbidities and chronic fatigue in severe acute respiratory syndrome survivors: Long-term follow-up

Parasomnia among psychiatric outpatients: A clinical, epidemiologic, crosssectional study

Abbreviated PTSD checklist (PCL) as a guide to clinical response

The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients

A community-based study of risk factors for probable rapid eye movement sleep behavior disorder

Probable RBD and association with neurodegenerative disease markers: A population-based study

Secondary "incidental" REM sleep behavior disorder: Do we ever think of it?

Acute hypokinetic-rigid syndrome following SARS-CoV-2 infection

Evening-types show highest increase of sleep and mental health problems during the COVID-19 pandemic -multinational study on 19,267 adults

Insomnia, anxiety, and depression during the COVID-19 pandemic: An international collaborative study

Dreamlike mentations during sleepwalking and sleep terrors in adults

Sleep and circadian problems during the coronavirus disease 2019 (COVID-19) pandemic: The international COVID-19 sleep study (ICOSS)

A single-question screen for rapid eye movement sleep behavior disorder: A multicenter validation study

Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: A multicentre study

Prevalence of stress, anxiety, depression among the general population during the COVID-19 pandemic: A systematic review and meta-analysis. Globalization and Health

Parkinsonism risk factors in Salt Lake City

Prevalence of REM sleep behavior disorder in Sun City

Factors associated with dream enacting behaviors among US farmers

Fight or flight? Dream content during sleepwalking/sleep terrors vs. rapid eye movement sleep behavior disorder

Prevalence of chemosensory dysfunction in COVID-19 patients: A systematic review and meta-analysis reveals significant ethnic differences

Prevalence and correlates of REM sleep behaviour disorder in patients with major depressive disorder: A two-phase study

Retrieved from https://covid19.who.int/ World Population Prospects

Risk factors for possible REM sleep behavior disorder: A CLSA population-based cohort study

Risk factors for Phenoconversion in rapid eye movement sleep behavior disorder

Dream-enactment behaviours during the COVID-19 pandemic: an international COVID-19 sleep study