SARS-CoV-2 infection is associated with increased odds of insomnia, RLS and dream enactment behavior.

Background: Literature suggests that the COVID-19 pandemic has resulted in poor sleep quality, especially among the infected population. However, literature regarding the effect of COVID-19 pandemic and SARS-CoV-2 infection on occurrence of insomnia, restless legs syndrome and dream enactment behavior is either scarce or unavailable.
Methods: This study was planned to assess the effect of SARS-CoV-2 infection on the occurrence of insomnia, restless legs syndrome (RLS) and dream enactment behavior (DEB). For this cross-sectional study, a questionnaire comprising of items related to demographic details, past medical history, and information related to SARS-CoV-2 infection was distributed through social media. Insomnia was diagnosed using clinical criteria. RLS, DEB, sleep quality, depression and anxiety were assessed using a validated questionnaire. Information regarding the use of hypnotic medications was also gathered.
Results: Of the 1596 respondents, 37.2% reported disturbed sleep while insomnia was reported by 22.6% respondents. 27.3% of respondents reported RLS and 17.4% suffered DEB. The odds of insomnia were greater among males (OR = 1.27; 95% CI: 1.03-1.58; P < 0.02) and among those who had SARS-CoV-2 infection (OR = 1.76; 95% CI = 1.42-2.19; P < 0.001). Similarly, SARS-CoV-2 infection was also associated with increased odds of RLS (OR = 2.48; 95% CI = 1.98-3.11; P < 0.001) and DEB (OR = 1.58; 95%CI = 1.21-2.06; P < 0.001). Insomnia, RLS and DEB were more frequent among respondents who required oxygen therapy, those who experienced loss of taste and/or smell, depression and anxiety. Prevalence of insomnia, DEB and RLS was higher than said prevalence among respondents with no history of SARS-CoV-2 infection, but lower than that of those with positive history of SARS-CoV-2 infection. 5.3% of respondents reported taking hypnotic medications before infection, 7% during infection and 5.3% after infection.
Conclusion: SARS-CoV-2-infection-related factors in association with environmental factors have increased the prevalence of insomnia, DEB and RLS among subjects having infection. SARS-CoV-2-associated immunological changes, hypoxia and neurotropism may play a role in occurrence of insomnia, DEB and RLS. Copyright:

INTRODUCTION

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shook the world in 2020–21 and led to a widespread disease that involved almost all of the continents of the world. The pandemic was associated with a number of limitations in lifestyle, affecting a large population across the globe, e.g., social seclusion, absence of structured routine, lack of exposure to light- and dark-cycles and deranged social rhythm.[1] A number of studies have been conducted to assess the sleeping patterns of the population during this period. Available systematic reviews and meta-analyses suggest that prevalence of disturbed sleep, depressive and anxiety symptoms were higher among the general population, patients having SARS-CoV-2 infection, and healthcare workers (HCWs) compared to pre-pandemic time.[23456]

It has been reported that disturbed sleep was most prevalent in patients suffering from SARS-CoV-2 infection, whereas its prevalence was lower in HCWs and the general population.[2] However, in these studies, a specific group of subjects was included from different geographical areas using a variety of methods to assess insomnia, sleep quality, depression and anxiety.[23456] A previous study from our group showed that the COVID-19 pandemic was associated with changes in circadian timing of sleep; however, prevalence of poor sleep quality remained unchanged.[7] Sleep regulation and sleep disorders are influenced by the interaction of a number of factors that include genetic, environmental, social rhythm, exercise as well as health status of the body.

However, a significant gap exists in the available literature. A careful search was made in three engines, that is, Google Scholar, EMBASE and PubMed, of the terms “SARS-CoV-2 infection” OR “COVID-19” OR “COVID-19 symptoms” AND “insomnia” OR “Restless legs syndrome” OR “REM sleep behavior disorder”. Prevalence of insomnia has been reported to vary between 15%–42% across studies during the pandemic.[89101112] However, these studies have used questionnaires that are used for assessment of severity of insomnia in the past seven days for the diagnosis of insomnia. Moreover, SARS-CoV-2 infection is also associated with significant hypoxemia in a number of patients, which increases the risk of developing restless legs syndrome (RLS). However, literature comparing the prevalence of RLS between subjects with and without SARS-CoV-2 infection could not be found. In addition to this, a number of studies have shown that dream frequency increased and the content of dreams became distressing during the COVID-19 pandemic.[131415] Anxiety and disrupted sleep in the presence of distressing dreams may pave way for dream enactment behavior (DEB), however, literature assessing an association between the two could not be traced.[16] Lastly, literature reporting an association between symptoms of SARS-CoV-2 infection that suggest neurotropism and risk of developing sleep disorders (insomnia, RLS and REM sleep behavior disorder) could not be found.[17]

Thus, the present study was planned to study the effect of SARS-CoV-2 infection to the occurrence of insomnia, RLS and DEB. In addition, predictors of insomnia, RLS and DEB were also investigated.

METHODS

This study was conducted through an online survey method after obtaining approval from the institutional ethics committee. A survey form was designed using Google Forms (Google Inc., USA). Participants were approached through various social media sites like WhatsApp, Facebook and LinkedIn by sending a link to the survey. The purpose of the study was explained in the information sheet placed at the beginning of the form, and participants were provided an option to participate in the study by choosing either “yes” or “no” in response to “Do you agree to participate in the study?”. Participants were requested to share the survey forms with their friends and relatives. The survey started on 1 June 2021 and closed on 16 June 2021. To encourage participation, the form was designed in such a way that the respondent could either choose a response from a drop-down menu or mark it using check-boxes (vide infra). This led to categorization of most of the data.

In the information sheet, the following subjects were requested not to participate in the study: subjects taking treatment for neurological or psychiatric disorders (excluding insomnia) at the time of enrolment in the study, subjects aged less than 18 years and pregnant women. Data regarding demographic variables, past medical history, information regarding SARS-CoV-2 infection, perceived sleep disturbance, subjective sleep quality, RLS, snoring, DEB, use of hypnotic medications, anxiety and depressive features was gathered. Information was gathered in English as well as in Hindi languages. Hindi translation was done following a standard method.[18]

Demographic data and past medical history

Data regarding gender, age, occupation and state of residence (drop-down menu) was collected. Age was divided into various categories, namely, 19–30 years; 31–50 years; 50–70 years and more than 70 years. Participants marked all of the following responses that were applicable to them to convey history of medical illness, e.g., diabetes mellitus, hypertension, asthma, chronic obstructive pulmonary disease (COPD), thyroid disorder, coronary artery disease. Provision was given to mark “None of the above” and to respond as text if any other medical disorder was diagnosed.

COVID-19 related information

Information was collected whether they had ever contracted SARS-CoV-2 infection or not by selecting one of the responses to the item “Did you suffer COVID infection diagnosed by a physician during pandemic?”. Those providing an affirmative answer were requested to elaborate details, namely, when they had SARS-CoV-2 infection (ranging between currently suffering to past one year); marking all the major symptoms of SARS CoV-2 infection that they experienced (cough, fever, shortness of breath, loss of taste and/or smell, body ache etc.); admission in hospital for SARS-CoV-2 infection (not required, general ward with or without oxygen, intensive care unit); and subjective recovery from SARS-CoV-2 infection (complete or incomplete). Subjects who had incomplete recovery were requested to provide the symptoms that they were experiencing after being declared recovered from acute infection.

Sleep disturbance

Subjects were given a choice to choose one response from a dichotomous response to an item, “Have you noticed any sleep disturbances or dissatisfaction with your sleep recently?”.

Insomnia

Subjects were asked to compare their sleep to the pre-pandemic time or before they contracted SARS-CoV-2 (if applicable). Details regarding insomnia were explored by asking whether they had noticed any difficulty in falling asleep, staying asleep, waking up earlier than the desired time or experiencing a combination of these symptoms. In addition, daytime symptoms after a night of poor sleep, e.g., fatigue, tiredness, headache, difficulty concentration, and irritability were also asked. For each of these items, subjects provided a response on one of the four choices: “recently appeared”, “worsened”, “same as before” and “improved”. Respondents were requested to provide details regarding frequency (nights per week) and duration of symptoms (more than or less than three months).

Those who reported at least one night-time symptom and at least one daytime symptom which “recently appeared”, or “worsened”, or remained “same as before” were considered suffering from insomnia according to standard criteria.[19] Those who had symptoms for “more than 3 months” and “3 or more nights a week” were categorized as chronic insomnia, whereas those reporting symptoms for “less than 3 months” and “3 or more nights a week” were marked as short term insomnia. Subjects who had symptoms for less than three nights a week, irrespective of duration or reported night-time symptoms in absence of daytime symptoms, were considered as having “insomnia symptoms”. Those reporting “improved” were considered as having past history of insomnia.

Restless legs syndrome

RLS was screened using single question for rapid screening.[20] This has been found to have 100% sensitivity and 96.8% specificity to diagnose RLS.[20] Subjects were asked to compare symptoms before COVID-19 pandemic or before they suffered SARS-CoV-2 infection (if applicable) and then to provide a response with one of the four choices: “recently appeared”, “worsened”, “same as before”, and “improved”. Those who reported that symptoms have “recently appeared”, or “worsened”, or remained “same as before” were considered suffering from RLS according to standard criteria for the present study.[19] Those reporting “improved” were considered as having past history of RLS.

Dream enactment behavior

Dream enactment behavior (DEB) was screened using the REM Sleep Behavior Disorder Single-Question Screen (RBD1Q).[21] Subjects were asked to compare symptoms before the COVID-19 pandemic or before they suffered SARS-CoV-2 infection (if applicable). This questionnaire was developed and validated to screen REM sleep behavior disorder (RBD) and has a 93.8% sensitivity and 87.2% specificity using polysomnography.[21] However, DEB similar to RBD may appear during non-REM sleep as well, especially under conditions that disrupt the sleep.[16] Hence, respondents proving any of the following responses, that is, “recently appeared”, or “worsened”, or remained “same as before” were considered suffering from DEB according to standard criteria.[19] Those reporting “improved” were considered as having past history of DEB.

Sleep quality

Sleep quality was assessed using single question.[22] Subjects were asked to respond on a continuous scale ranging from 1 to 10 about their sleep quality for the past seven days. Scores ranging from 0 to 3 were considered as having poor sleep quality, 4 to 6 fair sleep quality, 7 to 9 as good sleep quality, and 10 as excellent sleep quality.[22] This questionnaire was validated against the Pittsburgh Sleep Quality Index (PSQI). Concurrent validity, divergent validity, as well as, test–retest reliability have been found excellent among patients suffering from insomnia and depression.[22]

Depression and anxiety

Depression and anxiety were screened using Patient Health Questionnaire 4 items (PHQ-4)[23] PHQ-4 assesses symptoms during the past two weeks on a four-point Likert’s scale: Not at all, several days, more than half a day, and nearly every day. This has been validated in the general population. Score of 5 on PHQ-2 and GAD-2 correspond to 99 and 99.2 percentile risk for depression and anxiety, respectively.[23]

Medications for disturbed sleep

Subjects were asked whether they have been given any medication to improve sleep before, during or after COVID-19 pandemic or catching SARS-CoV-2 infection (if applicable). They were also requested to provide the name of the medication.

Statistical analysis

Statistical analysis was done using Statistical Package for the Social Sciences (SPSS) version 22.0 for Windows (IBM Corp. Released 2014. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp.). Data was checked for missing entries and frequency of each variable. Responses with missing variables that precluded the meaningful information were discarded. Variables with small frequency were collapsed with other categories. Chi-squared test was done to assess probabilities of categorical variables. At places where tables were larger than 2 × 2, post hoc analysis was done using adjusted residual approach after Bonferroni correction.[24] Variables that appeared significant in univariate analysis were included in the multiple logistic regression model.

RESULTS

A total of 1860 subjects responded to the survey. One thousand five hundred ninety-six subjects were included in the final analysis as others met any of the exclusion criteria or were not willing to participate or.

Demographic data

Subjects belonged to 22 states and union territories of India. Forty-five (44.6%) subjects were engaged in essential duties during the pandemic (HCWs, law enforcement agencies, etc.), 12.8% were self-employed, 4.6% were retired, 13.5% students, 8.3% were home-makers and others were working in non-essential services. Other data is shown in Table 1.

Table 1

Comparison of participants with and without history of SARS-CoV-2 infection

Variable	SARS-CoV-2 Negative (n=925)	SARS-CoV-2 Positive (n=671)	P	Remarks
Age (Years)
19-30	295 (31.9%)	166 (24.7%)*	X2=11.16; df=2; P=0.004	Adjusted Alpha (P<0.008)
31-50	484 (52.3%)	403 (60.1%)*
>51	146 (15.8%)	102 (15.2%)
Gender
Male	511 (55.2%)	407 (60.7%)	X2=4.66; df=1; P=0.03	-
Comorbidity
Asthma/COPD	38 (4.1%)	39 (5.8%)	X2=10.42; df=3; P=0.01
HTN and/or DM	161 (17.4%)	152 (22.7%)
Others	93 (10.1%)	58 (8.6%)
Sleep Disturbance
Present	281 (30.4%)	323 (48.1%)	X2=52.14; df=1; P<0.001	-
Frequency of symptoms
< 3 Nights/Week	149 (16.1%)	168 (25%)*	X2=46.51; df=2; P<0.001	Adjusted Alpha (P<0.008)
> 3 Nights/Week	142 (15.4%)	156 (23.2%)
Duration of Symptoms
< 3 months	151 (16.3%)	209 (31.1%)*	X2=56.31; df=2; P<0.001	Adjusted Alpha (P<0.008)
> 3 months	137 (14.8%)	112 (16.7%)
Insomnia reported	238 (25.7%)	255 (38%)	X2=27.44; df=1; P<0.001
Insomnia Type
Acute Insomnia	49 (5.3%)	78 (11.6%)*	X2=39.19; df=3; P<0.001	Adjusted Alpha (P<0.006)
Chronic	79 (8.5%)	54 (8%)
Other	110 (11.9%)	123 (18.3%)*
RLS	179 (19.4%)	257 (38.3%)	X2=70.33; df=1; P<0.001
Sleep quality
Terrible sleep	17 (1.8%)	8 (1.2%)	X2=35.28; df=4; P<0.001	Adjusted Alpha (P<0.005)
Poor sleep	51 (5.5%)	74 (11%)*
Fair sleep	238 (25.7%)	205 (30.6%)
Good sleep	451 (48.8%)	314 (46.8%)
Excellent sleep	168 (18.2%)	70 (10.4%)*
Anxiety	42 (4.5%)	37 (5.5%)	X2=0.78; df=1; P=0.37	-
Depression	46 (5%)	40 (6%)	X2=0.74; df=1; P=0.388	-
Use of Hypnotics
Before COVID-19	41 (4.4%)	44 (6.6%)	X2=3.48; df=1; P=0.06
During COVID-19	31 (3.4%)	80 (11.9%)	X2=44.15; df=1; P<0.001
After COVID	27 (2.9%)	58 (8.6%)	X2=25.27; df=1; P<0.001

*Cells were significant during post hoc analysis after Bonferroni correction

Past medical history

Approximately two-thirds of the respondents (67.3%) did not report having any medical disorder. Thyroid disorders were reported by 6.5% of subjects [Table 1].

SARS-CoV-2 infection

Nearly 42% of respondents reported having suffered from SARS-CoV-2 infection. 50.3% reported that they experienced loss of taste and/or smell during infection, 18.9% reported a combination of upper respiratory tract symptoms, fatigue and diarrhea, 13.1% had headache and remaining had other symptoms.

Of the subjects having SARS-CoV-2 infection (n = 671), 23.5% had it within 7–12 months before the survey, 16% during 3–6 months before survey, 57.3% had within past two months and 2.9% were suffering from SARS-CoV-2 infection at the time of survey. Most of the participants (80.1%) did not require admission, 11.3% were admitted without oxygen, 5.5% required oxygen during admission and 2.9% were admitted in intensive care unit. 39.3% respondents reported that they had some symptoms even after declared free of acute SARS-CoV-2 infection. Fatigue was the most common residual symptom (19.3%), followed by headache and loss of taste and/or smell as (6.8% subjects in each category). Subjects with and without SARS-CoV-2 infection were comparable with regards to gender distribution [Table 1].

Sleep disturbances

Of all participants, 37.2% reported disturbed sleep. Five percent (5.3%) subjects reported taking hypnotic medications before SARS-CoV-2 infection, 7% during infection and 5.3% after infection. Only 1.75% of respondents had hypnotic prescription through all three phases. SARS-CoV-2 infection increased the risk for insomnia, poor sleep quality, DEB and RLS [Table 1].

Acute and chronic insomnia was reported by 8% and 8.3% of, respectively, while other insomnia was most prevalent (14.6%). Subjects with and without insomnia were comparable with regards to age (P = 0.49). However, odds of insomnia were greater among males (OR = 1.27; 95% CI: 1.03–1.58; P < 0.02) and those who had SARS-Cov-2 infection (OR = 1.76; 95% CI = 1.42–2.19; P < 0.001). Insomnia was associated with poor-to-fair sleep on post hoc analysis (P < 0.001). Other details are provided in Table 2. Figure 1 shows the status of subtypes of insomnia before and after the pandemic between respondants with and without SARS-CoV-2 infection. Some of the participants having insomnia were taking hypnotic medications [Supplementary Figure 1].

Table 2

Comparison of subjects with and without clinical insomnia, RLS and DEB (n=1596)

Variable	Sleep Disorders		P	Remarks
Insomnia
	No insomnia (n=1103)	Insomnia present (n=493)
Comorbidity
Asthma/COPD	36 (3.3%)	41 (8.3%)*	X2=69.45; df=3; P<0.001	Adjusted Alpha (P<0.006)
HTN and/or DM	181 (16.4%)	131 (26.8%)*
Others	86 (7.8%)	65 (13.2%)*
Time of COVID infection
Within 2 months	255 (23.1%)	150 (30.4%)*	X2=27.88; df=2; P<0.001	Adjusted Alpha (P<0.0083)
3-12 months	161 (14.6%)	105 (21.3%)*
Hospital admission
No oxygen required	394 (35.7%)	220 (44.6%)*	X2=43.41; df=2; P<0.001	Adjusted Alpha (P<0.0083)
With oxygen	22 (2%)	35 (7.1%)*
COVID symptoms
Loss of taste and smell	334 (30.3%)	219 (44.4%)*	X2=31.2; df=2; P<0.001	Adjusted Alpha (P<0.0083
Others	82 (7.4%)	36 (7.3%)
Anxiety	25 (2.3%)	54 (11%)	X2=54.64; df=1; P<0.001	-
Depression	42 (3.6%)	44 (10.1%)	X2=46.54; df=1; P<0.001	-
Restless legs Syndrome
	No RLS (n=1160)	RLS (n=436)
Comorbidity
Asthma/COPD	54 (4.7%)	23 (5.3%)	X2=14.73; df=3; P=0.002	Adjusted Alpha (P<0.00625)
HTN and/or DM	203 (17.5%)	110 (25.2%)*
Others	106 (9.1%)	45 (10.3%)
Time of COVID infection
Within 2 months	254 (21.9%)	151 (34.6%)*	X2=70.86; df=2; P<0.001	Adjusted Alpha (P<0.0083)
3-12 months	160 (13.8%)	106 (24.3%)*
Hospital admission
No oxygen required	386 (33.3%)	228 (52.3%)*	X2=75.29; df=2; P<0.001	Adjusted Alpha (P<0.0083)
With oxygen	28 (2.4%)	29 (6.7%)*
COVID symptoms
Loss of taste and smell	339 (29.2%)	214 (49.1%)*	X2=70.58; df=2; P<0.001	Adjusted Alpha (P<0.0083)
Others	75 (6.5%)	43 (9.9%)
Anxiety	41 (3.5%)	38 (8.7%)	X2=18.08; df=1; P<0.001
Depression	42 (3.6%)	44 (10.1%)	X2=26.02; df=1; P<0.001
Dream Enactment Behaviour (DEB)
	No DEB (n=1328)	DEB (n=268
Comorbidity
Asthma/COPD	57 (4.3%)	20 (7.5%)	X2=9.42; df=3; P=0.02	Adjusted Alpha (P<0.00625)
HTN and/or DM	253 (19.1%)	60 (22.4%)
Others	121 (9.1%)	30 (11.2%)
Time of COVID infection
Within 2 months	324 (24.4%)	81 (30.2%)*	X2=12.03; df=2; P=0.002	Adjusted Alpha (P<0.0083)
3-12 months	209 (15.7%)	57 (21.3%)*
Hospital admission
No oxygen required	497 (37.4%)	117 (43.7%)	X2=23.62; df=2; P<0.001	Adjusted Alpha (P<0.0083)
With oxygen	36 (2.7%)	21 (7.8%)*
COVID symptoms
Loss of taste and smell	434 (32.7%)	119 (44.4%)*	X2=13.84; df=2; P<0.001	Adjusted Alpha (P<0.0083)
Others	99 (7.5%)	19 (7.1%)
Anxiety	57 (4.3%)	22 (8.2%)	X2=7.27; df=1; P=0.007
Depression	62 (4.7%)	24 (9%)	X2=8.03; df=1; P=0.005

*Cells were significant during post hoc analysis after Bonferroni correction

Figure 1

Relationship between SARS-CoV-2 infection and Insomnia, Restless Legs Syndrome and Dream Enactment Behavior in study sample

Twenty seven percent of respondents (27.3%) reported RLS. Subjects with and without RLS were comparable with regards to age (P = 0.04, with no significant difference across cells on post hoc analysis) and gender (P = 0.06). SARS-CoV-2 infection (OR = 2.48; 95% CI = 1.98–3.11; P < 0.001) increased the odds of developing RLS. RLS was associated with poor-to-fair sleep on post hoc analysis (P < 0.001). Other details are provided in Table 2. Figure 1 shows the status of RLS before and after the pandemic between respondents with and without SARS-CoV-2 infection.

Nearly one-fifth of respondents (17.4%) reported DEB in the present study. Subjects with and without DEB were comparable with regards to age and gender. SARS-CoV-2 infection increased the odds of developing DEB (OR = 1.58; 95%CI = 1.21–2.06; P < 0.001). It was present in subjects who experienced loss of taste and/or smell (P < 0.001), and who had depression (P = 0.005) and anxiety (P = 0.007). No association was observed with sleep quality on post hoc analysis. Further details are provided in Table 2. Figure 1 shows the relationship between DEB and SARS-CoV-2 infection.

Nearly one-third of respondents (27.2%) reported sleep quality ranging from terrible to fair. Female gender (P < 0.001), and presence of depression (P < 0.001) and anxiety (P < 0.001) worsened sleep quality. Similarly, sleep quality was poor among respondents who had SARS-CoV-2 infection (P < 0.001), especially in those with recent infection (past two months, P < 0.001), those who experienced loss of taste and/or smell (P < 0.001) and those who did not require oxygen (P < 0.001). Details are presented in supplementary Table 1.

Suppl Table 1

Comparison of subjects with and without poor sleep quality (n=1596)

Variable	Poor sleep quality (n=593)	Good sleep quality (n=1003)	P	Remarks
Age (Years)
19-30	175 (29.5%)	286 (28.5%)	0.424	-
31-50	335 (56.5%)	552 (55%)
>51	83 (14%)	165 (16.5%)
Gender
Male	306 (51.6%)	612 (61%)	<0.001*	-
Comorbidity
Asthma/COPD	40 (6.7%)	37 (3.7%)	<0.001*	Post-hoc sig. (P<0.00625) in Asthma/COPD and others group.
HTN &/or DM	125 (21.1%)	188 (18.7%)
Others	80 (13.5%)	71 (7.1%)
COVID positive	287 (48.4%)	384 (38.3%)	<0.001*	-
Time of COVID infection
Within 2 months	194 (32.7%)	211 (21%)	<0.001*	Post-hoc significant (P<0.0083) in the “within 2 months” group.
3-12 months	93 (15.7%)	173 (17.2%)
Hospital admission
No oxygen required	257 (43.3%)	357 (35.6%)	<0.001*	Sig. (P<0.0083) on post-hoc in the group receiving no oxygen.
With oxygen	30 (5.1%)	27 (2.7%)
COVID symptoms
Loss of taste and smell	246 (41.5%)	307 (30.6%)	<0.001*	Post-hoc sig. (P<0.0083) in the group with loss of taste and smell.
Others	41 (6.9%)	77 (7.7%)
Anxiety	47 (7.9%)	32 (3.2%)	<0.001*	-
Depression	54 (9.1%)	32 (3.2%)	<0.001*	-
Sleep disturbance	420 (70.8%)	184 (18.3%)	<0.001*
Frequency of sleep disturbance
<3 nights/week	179 (30.2%)	138 (13.8%)	<0.001*	Post-hoc sig. (P<0.0083) in both groups)
>3 nights/week	246 (41.5%)	52 (5.2%)
Duration of sleep disturbance
<3 months	252 (42.5%)	108 (10.8%)	<0.001*	Post-hoc sig. (P<0.0083) in both groups)
>3 months	170 (28.7%)	79 (7.9%)
RLS	220 (37.1%)	216 (21.5%)	<0.001*	-
Insomnia	360 (60.7%)	133 (13.3%)	<0.001*	-
Dream Enactment Behaviour	132 (22.3%)	136 (13.6%)	<0.001*	-

Depression and anxiety were reported by 5.4% and 4.9% of respondents, respectively. The proportion of depression and anxiety was higher in participants who experienced SARS-CoV-2 infection.

DISCUSSION

This study showed that poor sleep quality was reported by one-fourth of the respondents. Nearly one-third of participants reported insomnia, and the proportion of RLS was nearly ten times of the population prevalence of the geographical area. Similarly, prevalence of DEB was also higher than the general population. Anxiety, depression, need for oxygen therapy and other medical comorbidities increased the risk of these sleep disorders in the multivariate analysis model [Table 3].

Table 3

Logistic Regression analysis of the factors associated with insomnia, RLS and DEB

Variables	B	P	Odds ratio	95% CI
Insomnia
Time of COVID illness onset	0.06	0.70	1.06	(0.75-1.50)
Requirement of oxygen	0.82	0.006*	2.27	(1.26-4.09)
Presence of comorbidities	1.04	<0.001*	2.84	(2.02-3.98)
Loss of taste and smell	0.44	0.059	1.55	(0.98-2.45)
Anxiety	1.12	0.020*	3.07	(1.19-7.92)
Depression	0.59	0.191	1.81	(0.74-4.46)
Restless Legs Syndrome
Time of COVID illness onset	0.10	0.54	1.10	(0.80-1.52)
Requirement of oxygen	0.54	0.054	1.72	(0.99-3.01)
Presence of comorbidities	0.03	0.81	1.03	(0.74-1.44)
Loss of taste and smell	0.08	0.70	1.08	(0.71-1.64)
Anxiety	0.04	0.92	1.04	(0.42-2.57)
Depression	0.92	0.037*	2.52	(1.05-5.99)
Dream Enactment Behavior
Time of COVID illness onset	0.04	0.83	1.04	(0.70-1.54)
Requirement of oxygen	0.83	0.006*	2.29	(1.27-4.12)
Presence of comorbidities	0.25	0.20	1.28	(0.87-1.88)
Loss of taste and smell	0.36	0.18	1.43	(0.83-2.45)
Anxiety	0.20	0.70	1.23	(0.42-3.56)
Depression	−0.04	0.93	0.95	(0.33-2.74)

A number of studies have reported poor sleep quality during the COVID-19 pandemic in a variety of populations ranging from the general population to special populations like healthcare workers and subjects suffering from SARS-CoV-2 infection.[2345625] These studies have shown that the proportion of poor sleep quality ranges from 34% to 44%.[2345625] In the present study, the proportion of poor sleep quality was comparable to the figures of the studies that were conducted during the COVID-19 pandemic, and was greater than the population prevalence seen before COVID-19 pandemic in the same geographical area (18.4%).[26]

Only a few studies have assessed the effect of the pandemic and SARS-CoV-2 infection on insomnia.[89101112] These studies showed that prevalence of insomnia ranged between 15% and 42% during the pandemic.[89101112] The studies included used the Insomnia Severity Index[27] or Athens Insomnia Scale[28] which are primarily measures of severity of insomnia and included a variety of populations, such as the general population,[812] patients having SARS-CoV-2 infection,[910] and patients who recovered from SARS-CoV-2 infection.[11] These studies showed a higher prevalence of insomnia among all groups: general population, frontline and healthcare workers, as well as, among patients currently experiencing or recovered from SARS-CoV-2 infection compared to pre-pandemic time.[891011] Results of these studies suggested that the proportion of insomnia was highest among admitted patients followed by COVID-19 survivors and was lowest in the general population. In the present study, using an online structured questionnaire based on the most recent diagnostic criteria for insomnia (however, not validated), also reported that the prevalence of insomnia has increased since pre-pandemic time[19] and that it was higher among those who had experienced SARS-CoV-2 infection compared to ‘‘No SARS-CoV-2 infection” group [Table 1]; these are similar to the results of previous reports.[89101126] Multiple regression analysis in this study showed that oxygen therapy, comorbidity and other medical disorders increased the risk of insomnia [Table 3], which were not reported in the above-mentioned studies. These factors could have played a role in the occurrence of insomnia in a multitude of pathways. For example, these factors are indirectly related to greater respiratory distress, damage to lung parenchyma, hospitalization particularly in high dependency units or intensive care units and complexity of medical management, which are known risk factors of insomnia.[29] Directly, hypoxemia can also increase the risk of insomnia among patients who have sleep disordered breathing and cardiovascular illness, especially when 1.5% of sleep time was spent below the oxygen saturation of 90%.[30] Hypoxia is known to increase sleep onset latency, frequent awakenings from sleep and disrupt the circadian clock.[313233] All of these factors can contribute to insomnia and DEB.[16]

To the best of our knowledge, the effect of SARS-CoV-2 infection and the COVID-19 pandemic on RLS and DEB have not been assessed, so far. The present study reported that one-fourth of the respondents reported RLS and 17% reported DEB. Proportion of RLS in the present study was nearly ten times higher than the prevalence of RLS in the general population from the same geographical area.[3435] Franco et al.,[36] in a theoretical review, suggested that depression and reduced physical activity during the pandemic may initiate or exacerbate RLS. Though physical activity was not examined in the present study, depressive symptoms were found to increase the risk of RLS, as suggested in the above theoretical review [Table 3]. Though the prevalence of DEB is not available from the geographical area of the present study, data from a population in United States of America has shown that DEB is commoner than what was previously thought.[37] However, disrupted sleep and hypoxemia are known risk factors of DEB, and the present study confirms findings of previous studies.[16]

Available literature suggests that the number of factors, e.g., anxiety, change in life style, altered circadian rhythm, lack of exercise and absence of structured routine are associated with insomnia, RLS and DEB.[891011121636] A previous study from the geographic area identical to the present study reported similar findings.[7] It is therefore possible that participants included in the present study were experiencing similar changes in routine and hence, experienced either worsening or appearance of these sleep disorders [Figure 1]. In addition, the pandemic has been associated with a change in dream content as well as associated emotions, which can pave way for DEB.[1316] Though this has not been investigated in the present study, in view of available literature, authors opine that it could have also played a role in reported occurrence of DEB in the present study.

Besides other factors discussed above, SARS-CoV-2-related systemic inflammation could have also played a role in the occurrence of insomnia and RLS.[38394041] However, markers of systemic inflammation were not examined in the present study.

Like any other scientific investigations, the present study also had some methodological limitations. First, the study sample included in the present study had all of the limitations that are common to online survey- absence of randomization, selection bias (survey could be filled by only participants who had access to internet), response bias (possibility of selective response by the participants who were experiencing sleep disturbances), recall bias. Second diagnosis of sleep disorders was based on online questionnaires rather than clinical diagnosis. Further studies should be planned, that include clinical and laboratory assessment of these disorders to improve the strength of evidence. Third, the survey was distributed through social media; hence, subjects who do not have access to the social media could not be included in the study. This limits generalization of the findings to the whole population. Fourth, being a survey, other factors that could have contributed to the sleep disorders, such as psychiatric disorders, neurological disorders and substance use disorders, were excluded through self-report. Fifth, other factors that contribute to DEB, RLS and insomnia (viz., family history) could not be assessed in the present study. This is an important area and requires further investigation. However, this study had a number of strengths. Contrary to earlier studies, where insomnia was diagnosed using cutoff scales that capture data for 1–2 week, diagnosis of insomnia in the present study was made using clinical criteria.[9101112] Secondly, at times, subjects may mistakenly report restlessness associated with anxiety as RLS. Logistic regression analysis suggested that this was not the case in the present study. Third, the effect of medications on sleep disorders was carefully investigated. Fourth, this study included subjects from all corners of a large nation.

In conclusion, the present study reports that SARS-CoV-2-related factors, in association with environmental factors (hospitalization, emotional stress, medications to name a few), have increased the prevalence of insomnia, DEB and RLS. Though this was a preliminary study with several methodological limitations, the results suggest that a systematic, well-designed investigation should be carried out in this area, especially when reports are appearing in scientific literature mentioning a high prevalence of psychiatric morbidities, sleep disorders and long-term consequences of SARS-CoV-2 infection. Moreover, with multiple variants of SARS-CoV-2 virus appearing, the pandemic does not appear to end soon.

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Conflicts of interest

There are no conflicts of interest.

Prescription of hypnotics among subjects having insomnia (N=1596)