Primary Outcomes

Description: Percent of participants randomized to PEER who attend at least three group sessions

Measure: Intervention engagement

Time: 12 weeks

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Description: Percent of sampled PEER group sessions in which the peer coaches were adequately adherent (i.e., average score equal to "acceptable" and no items scored as "unacceptable") on the PEER fidelity measure

Measure: Intervention fidelity

Time: 12 weeks

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Description: Attendance- mean number of supervised fitness training sessions attended

Measure: Attendance- mean number of supervised fitness training sessions attended

Time: 12 weeks

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Description: Weekly step-counts will be measured by pedometer

Measure: Change from baseline in Ambulatory Physical Activity

Time: 12 weeks

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Description: Maximum rate of oxygen consumption as measured during incremental exercise on a motorized treadmill

Measure: Change from baseline in Maximal Aerobic Capacity (Vo2Max)

Time: 12 weeks

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Primary Outcomes

Description: data from National registers

Measure: Changes in degree of sick leave

Time: From 2 years prior to intervention - to 4 years after intervention

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Description: data from patients self-report

Measure: Changes in degree of sick leave

Time: From 2 years prior to intervention - to 4 years after intervention

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Description: Changes in depressive symptoms measured by Beck Anxiety Inventory (BAI)

Measure: Changes in anxiety symptoms

Time: From pre treatment, to post treatment (12 weeks), 6 months and 1 year follow-up

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Description: Changes in depressive symptoms measured by Beck Depression Inventory II (BDI-II)

Measure: Changes in depressive symptoms

Time: From pre treatment, to post treatment (12 weeks), 6 months 1 year follow-up

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Secondary Outcomes

Description: Changes in metacognitions symptoms measured by the Metacognitions Questionnaire 30 (MCQ-30)

Measure: Changes in metacognitions

Time: From pre treatment, to post treatment (12 weeks), 6 months and 1 year follow-up

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Description: Changes in symptoms measured by Subjective Health Complaints

Measure: Changes in subjective health complaints

Time: From pre treatment, to post treatment (12 weeks), 6 months and 1 year follow-up

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Description: Changes in measured Negative Acts Questionnaire

Measure: Changes in bullying and victimisation at work

Time: From pre treatment, to post treatment (12 weeks), 6 months and 1 year follow-up

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Description: Changes measured with Return to work self-efficacy

Measure: Changes in self-efficacy

Time: From pre treatment, to post treatment (12 weeks), 6 months and 1 year follow-up

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Description: Changes measured with The resilience scale for adults (RSA)

Measure: Changes in resilience

Time: From pre treatment, to post treatment (12 weeks), 6 months and 1 year follow-up

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Description: Changes measured with EQ-5D-5L

Measure: Changes in quality of life

Time: From pre treatment, to post treatment (12 weeks), 6 months and 1 year follow-up

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Description: Diagnostic evaluations using MINI - International Neuropsychiatric Interview

Measure: MINI - diagnostic interview

Time: From pre treatment, to post treatment (12 weeks)

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Other Outcomes

Description: Sub-analyses taking into consideration the onset of Covid-19 in Norway by mid March 2020

Measure: Secondary analysis related to the onset of Covid-19

Time: From pre treatment, to post treatment (12 weeks), 6 months and 1 year follow-up

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Primary Outcomes

Description: The 6-minute walk test (6MWT) will be used to measure cardiorespiratory fitness (CRF) during which individuals will be asked to walk continuously for six minutes on a flat, indoor surface around cones (separated by 100ft). The possible distance range is 400 meters to 650 meters. Higher scores reflect better outcomes (greater physical fitness).

Measure: Difference in Participant's Total Distance During 6-minute Walk

Time: Baseline and the last study visit (Up to 20 weeks)

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Secondary Outcomes

Description: Mean difference in overall minutes spent walking per week from baseline to last study visit (up to 20 minutes). This information will be obtained from the participant's Fitbit. Higher scores reflect more minutes walking.

Measure: Mean Difference in Minutes Spent Walking

Time: Baseline and the last study visit (up to 20 weeks)

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Description: Mean difference in daily steps from baseline to last study visit (up to 20 weeks). This information will be obtained from the participants Fitbit. Higher scores reflect more daily steps.

Measure: Mean Difference in Daily Steps

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Mean difference in overall score from baseline to last study visit (up to 20 weeks). The UCLA Loneliness scale is a 20 item scale. Answers are on a 4 point scale with options "I often feel this way," "I sometimes feel this way," "I rarely feel this way," and "I never feel this way." Possible scores range from 20 to 80. Higher scores reflect worse outcomes (greater feelings of loneliness).

Measure: Mean Difference Overall UCLA Loneliness Scale Score

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Mean difference in the overall score from baseline to last study visit (up to 20 weeks). The PANSS is a semi-structured interview using a 30-item scale to evaluate the presence, absence and severity of Positive, Negative and General Psychopathology symptoms of schizophrenia. All 30 items are rated on a 7-point scale (1 = absent; 7 = extreme). Possible scores range from 30 to 210. Higher scores reflect worse outcomes (i.e. greater symptoms of psychosis).

Measure: Mean Difference Overall PANSS Score

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Mean difference in body weight change from baseline to last study visit (up to 20 weeks). Expected normal BMI ranges from 14 to 54. Higher scores reflect worse outcomes (i.e. greater body mass).

Measure: Mean Difference in Body Weight Change

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Mean difference in blood pressure change from baseline to last study visit (up to 20 weeks).

Measure: Mean difference in blood pressure change

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Mean difference in resting heart rate change from baseline to last study visit (up to 20 weeks). Expected normal heart rate ranges from 40 to 120. Higher scores reflect worse outcomes (poorer heart condition).

Measure: Mean Difference in Resting Heart Rate Change

Time: Baseline and the last study visit (Up to 20 weeks)

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Other Outcomes

Description: Mean difference in composite motivation score from baseline to last study visit (up to 20 weeks). The BREQ-2 is a 19 item self-report scale. Answers are on a 5 point Likert scale ranging from 0 to 4. 0 corresponds to "not true for me" and 4 corresponds to "very true for me." Possible scores range from 0 to 46. Higher scores reflect better outcomes (higher autonomous motivation to exercise).

Measure: Mean Difference in Composite Motivation Score on the Behavioral Regulation Exercise Questionnaire (BREQ-2)

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Mean difference in composite score from baseline to last study visit (up to 20 weeks). The BPNE is an 11 item self-report scale. Answers are on a 5 point Likert scale ranging from "I don't agree at all" to "I completely agree." Possible scores range from 11 to 55. Higher scores reflect better outcomes (i.e. more psychological needs being met through exercise).

Measure: Mean Difference in Composite Score on the Basic Psychological Needs in Exercise Scale (BPNES)

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Mean difference in composite score from baseline to last study visit (up to 20 weeks). 2. The PACES is an 18 item self-report scale. Answers are on a 7-point scale. Possible scores range from 18 to 126. Higher scores reflect better outcomes (greater enjoyment of physical activity).

Measure: Mean Difference in Composite Score on the Physical Activity Enjoyment Scale (PACES)

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Mean difference in composite score from baseline to last study visit (up to 20 weeks). The BPNS is a 21 item self-report scale. Answer are on a 7-point Likert scale ranging from "not at all true" to "very true." Possible scores range from 21 to 147. Higher scores reflect better outcomes (better autonomy, competence, and relatedness).

Measure: Mean Difference in Composite Score on the Basic Psychological Needs Scale (BPNS)

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Mean difference in composite score from mid-treatment to last study visit (up to 20 weeks). The Autonomy Scale is a 6 item self-report scale. Answers are made using a 7-point scale. Possible scores range from 7 to 46. Higher scores reflect better outcomes (better relationship between research participant and staff.

Measure: Mean Difference in Composite Score on the Autonomy Support Scale

Time: Baseline and the last study visit (Up to 20 weeks)

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Description: Total score at Post treatment visit only (16 weeks). The End of Study survey measures participant's satisfaction and feedback with the PACE-Life trial. The survey is a 18 item self-report scale, consisting of both Likert scale and open-ended items. Answers are made using a 5-point Likert scale. Possible scores range from 18-90. Higher scores reflect higher levels of satisfaction and enjoyment in the study.

Measure: End of Study Survey

Time: Post treatment only (16 weeks)

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Primary Outcomes

Description: WSAS is a simple and reliable measure of impaired functioning. Scores range from 0-40, with lower scores representing better functioning, scores 0-10 are considered subclinical, 11-20 associated with significant functional impairment but less severe clinical symptomology, and >20 suggest moderately severe functional impairment (Mundt et al. 2002).

Measure: Change from baseline Work and Social Adjustment Scale (WSAS) score at week 9 of study

Time: Measure completed at baseline (start of week 1) and week 9.

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Secondary Outcomes

Description: Social recovery will be measured using an adapted versions of the Time Use Survey (TUS) Structured Hours, which has been previously validated for use as a social recovery measure by Hodgekins, Fowler and colleagues, and utilised in the National EDEN study (Hodgekins et al. 2015; Hodgekins 2012; Fowler et al. 2009). This will be adapted to a reduced interview to include only those areas relevant to the social recovery measure, hence the Time Use Survey-Structured Hours (TUS-SH).

Measure: Time Use Survey - Structured Hours (TUS-SH)

Time: Measure completed in weeks 1, 5, 9, 13 and 17.

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Description: PHQ-9 is a self-administered measure of depression, which scores all 9 of the DSM-IV criteria for depression. Scores range from 0-27, with 5-9 indicating minimal symptoms, 10-14 minor depression, 15-19 moderately severe major depression and ≥20 severe major depression.

Measure: Patient Health Questionnaire (PHQ-9)

Time: Measure completed in weeks 1, 5, 9, 13 and 17.

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Description: iPad delivered cognitive test of sustained attention.

Measure: Rapid Visual Information Processing (RVP) / CANTAB Cognitive Test

Time: Measure completed in weeks 1, 5, 9, 13 and 17.

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Description: iPad delivered cognitive test of visual episodic memory.

Measure: Paired Associates Learning (PAL) / CANTAB Cognitive Test

Time: Measure completed in weeks 1, 5, 9, 13 and 17.

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Description: iPad delivered cognitive test of working memory and strategy.

Measure: Spatial Working Memory (SWM) / CANTAB Cognitive Test

Time: Measure completed in weeks 1, 5, 9, 13 and 17.

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Description: iPad delivered cognitive test of emotional recognition.

Measure: Emotion Recognition Task (ERT) / CANTAB Cognitive Test

Time: Measure completed in weeks 1, 5, 9, 13 and 17.

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Description: GAF is an assessment of psychological, social and occupational functioning along a hypothetical continuum of mental health/illness. It is suggested that symptom scale for degree of severity be considered to cover the past 3 days prior to assessment but time frames can be varied based on the intention of use (Aas 2011). However by utilising the split version of this measure, the symptom and function scores can be evaluated and considered independently. This has been shown to be highly consistent across experienced raters, so sufficient training and utilisation may be fundamental to its efficacy (Pedersen et al. 2007). Scores range from 0-100 with higher scores representing better functioning across symptomatic and functional domains (Hall 1995).

Measure: Global Assessment of Functioning (GAF) (split version / subscales GAF-D & GAF-S)

Time: Measure completed in weeks 1, 9 and 17.

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Description: WSAS is a simple and reliable measure of impaired functioning. Scores range from 0-40, with lower scores representing better functioning, scores 0-10 are considered subclinical, 11-20 associated with significant functional impairment but less severe clinical symptomology, and >20 suggest moderately severe functional impairment (Mundt et al. 2002).

Measure: Change from baseline Work and Social Adjustment Scale (WSAS) score at week 17

Time: Measure completed at baseline (start of week 1) and week 17.

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Description: WSAS is a simple and reliable measure of impaired functioning. Scores range from 0-40, with lower scores representing better functioning, scores 0-10 are considered subclinical, 11-20 associated with significant functional impairment but less severe clinical symptomology, and >20 suggest moderately severe functional impairment (Mundt et al. 2002).

Measure: Change from baseline Work and Social Adjustment Scale (WSAS) score at week 5, to correct for confounding in mediation analysis

Time: Measure completed at baseline (start of week 1) and week 5.

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Description: WSAS is a simple and reliable measure of impaired functioning. Scores range from 0-40, with lower scores representing better functioning, scores 0-10 are considered subclinical, 11-20 associated with significant functional impairment but less severe clinical symptomology, and >20 suggest moderately severe functional impairment (Mundt et al. 2002).

Measure: Change from baseline Work and Social Adjustment Scale (WSAS) score at week 13, to correct for confounding in mediation analysis

Time: Measure completed at baseline (start of week 1) and week 13.

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Other Outcomes

Description: SCI-8 this measure is validated against DSM-5 criteria for insomnia, including sleep quality and daytime function over the previous week. It is utilised within the Sleepio intervention and was the primary outcome measure for the OASIS randomised controlled trial (Freeman et al. 2017). This eight-item assessment questionnaire includes: 'concerns about getting to sleep, remaining asleep, sleep quality, daytime functioning, daytime performance, duration of sleep problem, nights per week having a sleep problem and extent troubled by poor sleep'(Espie, Kyle, Hames, et al. 2014). It has a robust internal consistency (α≥0.86) and showed convergent validity with the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) (Espie, Kyle, Hames, et al. 2014). Scores range from 0-32 with higher scores indicating better sleep, scores below 17 identifying insomnia in 89% of cases (Espie, Kyle, Hames, et al. 2014; Freeman et al. 2017).

Measure: Sleep Condition Indicator (SCI-8)

Time: Measure completed in weeks 1, 5, 9, 13 and 17.

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Description: ISI is a measure specifically designed as a brief self-administered measure of insomnia and outcomes for use in their treatment within research. It corresponds to the DSM-IV criteria for insomnia and measures perception and severity of symptoms within the previous 2 weeks. Scores range from 0-28, 0-7 indicating no significant insomnia, 8-14 sub threshold insomnia, 15-21 moderate clinical insomnia, and 22-28 severe clinical insomnia (Smith & Wegener 2003; Bastien et al. 2001). It has been validated as a web-based measure with internal consistency of ≥88% (Thorndike et al. 2011).

Measure: Insomnia Severity Index (ISI)

Time: Measure completed in weeks 1, 9 and 17.

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Description: PSQI is a self-report 19-item measure that retrospectively measures sleep quality and disturbances over the previous month. The domains of sleep quality included are: sleep wake patterns, duration of sleep, sleep latency, the frequency and severity of specific sleep-related problems and impact on daytime function. Scores range from 0-21, with higher scores indicating poorer sleep quality. The empirically derived cut-off score is >5 to distinguish poor sleepers with severe difficulties in at least 2 domains, or moderate difficulties in more than 3 domains. This cut-off correctly identifies 88.5% of patients, with a sensitivity of 89.6% and specificity of 86.5% (Buysse et al. 1989; Smith & Wegener 2003).

Measure: Pittsburgh Sleep Quality Index (PSQI)

Time: Measure completed in weeks 1, 9 and 17.

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Description: Nightly sleep diaries will be reported online using the Sleepio.com online diary. GENEActive actigraphy watch will collect raw data of activity. Which will record sleep patterns objectively. This will be compared with sleep diaries for consistency of subjective measure with objective measure. The actigraphy data will be considered for L5 (lowest 5 hours of activity) M10 (highest 10 hours of activity) and relative amplitude (ratio between L5 and M10). This will then be compared with the nightly sleep diaries for the same period to determine percentage of consistency of reporting.

Measure: Validation of Sleep Diaries by comparison with actigraphy activity data

Time: Monitoring will be done for a complete week just prior to week 1, during week 8 and 16. Sleep diaries are collected nightly during this same period.

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Description: This is a short 7 question (3 minute) survey to allow us to collect basic data on the impact of the ongoing pandemic on participants.

Measure: COVID-19 Brief Questionnaire (COVID-19-B)

Time: Measure completed in weeks 1, 5, 9, 13 and 17.

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Primary Outcomes

Description: The prevalence and incidence changes of common mental disorders (i.e. depression, anxiety, and PTSD) in a representative sample of Chinese adolescents

Measure: The prevalence and incidence changes of common mental disorders

Time: 15 Oct 2020 - 15 Nov 2020

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Secondary Outcomes

Description: To identify demographics (e.g. age, gender, education, family background, and residence) the major psychosocial factors (i.e. exposure to traumatic events, religious belief, social media exposure, loneliness, and perceived social support) contributing to prevalence and incidence of mental disorders

Measure: Mental disorders and its' correlates

Time: 15 Oct 2020 - 15 Nov 2020

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Primary Outcomes

Description: The 12-item version of the General Health Questionnaire (GHQ-12) is a self-reported instrument that measures symptoms of anxiety and depression. It provides cut-off points to identify people at risk of anxiety and/or depression, which differ slightly between countries

Measure: Anxiety and depressive symptoms

Time: 12 months

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Secondary Outcomes

Description: Ad hoc survey on experiences, fears, and concerns about Covid-19

Measure: Experiences, fears and concerns about the Covid-19

Time: Baseline

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Description: Ad hoc survey on experiences, fears, and concerns about Covid-19

Measure: Experiences, fears and concerns about the Covid-19

Time: 3 months

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Description: Ad hoc survey on experiences, fears, and concerns about Covid-19

Measure: Experiences, fears and concerns about the Covid-19

Time: 6 months

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Description: Ad hoc survey on experiences, fears, and concerns about Covid-19

Measure: Experiences, fears and concerns about the Covid-19

Time: 12 months

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Description: Ad hoc survey on Covid-19 training and resource prioritization

Measure: Training and resource prioritization

Time: Baseline

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Description: Ad hoc survey on Covid-19 training and resource prioritization

Measure: Training and resource prioritization

Time: 3 months

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Description: Ad hoc survey on Covid-19 training and resource prioritization

Measure: Training and resource prioritization

Time: 6 months

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Description: Ad hoc survey on Covid-19 training and resource prioritization

Measure: Training and resource prioritization

Time: 12 months

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Description: Item from the Columbia Suicide Severity Rating Scale (C-SSRS) that measures suicidal ideation with a dichotomous answer (presence/absence)

Measure: Suicide ideation (presence)

Time: Baseline

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Description: Item from the Columbia Suicide Severity Rating Scale (C-SSRS) that measures suicidal ideation with a dichotomous answer (presence/absence)

Measure: Suicide ideation (presence)

Time: 3 months

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Description: Item from the Columbia Suicide Severity Rating Scale (C-SSRS) that measures suicidal ideation with a dichotomous answer (presence/absence)

Measure: Suicide ideation (presence)

Time: 6 months

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Description: Item from the Columbia Suicide Severity Rating Scale (C-SSRS) that measures suicidal ideation with a dichotomous answer (presence/absence)

Measure: Suicide ideation (presence)

Time: 12 months

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Description: 5-point Likert item from the Columbia Suicide Severity Rating Scale (C-SSRS). Higher scores indicate higher frequency.

Measure: Suicide ideation (frequency)

Time: Baseline

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Description: 5-point Likert item from the Columbia Suicide Severity Rating Scale (C-SSRS). Higher scores indicate higher frequency.

Measure: Suicide ideation (frequency)

Time: 3 months

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Description: 5-point Likert item from the Columbia Suicide Severity Rating Scale (C-SSRS). Higher scores indicate higher frequency.

Measure: Suicide ideation (frequency)

Time: 6 months

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Description: 5-point Likert item from the Columbia Suicide Severity Rating Scale (C-SSRS). Higher scores indicate higher frequency.

Measure: Suicide ideation (frequency)

Time: 12 months

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Description: Ad hoc 3-item survey to evaluate acute stress disorder. Higher values of the 5-points Likert scales suggest higher frequency of symptoms

Measure: Acute stress symptoms

Time: Baseline

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Description: Ad hoc 3-item survey to evaluate acute stress disorder. Higher values of the 5-points Likert scales suggest higher frequency of symptoms

Measure: Acute stress symptoms

Time: 3 months

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Description: Ad hoc 3-item survey to evaluate acute stress disorder. Higher values of the 5-points Likert scales suggest higher frequency of symptoms

Measure: Acute stress symptoms

Time: 6 months

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Description: Ad hoc 3-item survey to evaluate acute stress disorder. Higher values of the 5-points Likert scales suggest higher frequency of symptoms

Measure: Acute stress symptoms

Time: 12 months

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Description: Ad hoc survey on support network. The answers to the multiple items will be adjusted so higher values indicate higher levels of psychological and social support

Measure: Psycho/social support and network

Time: Baseline

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Description: Ad hoc survey on support network. The answers to the multiple items will be adjusted so higher values indicate higher levels of psychological and social support

Measure: Psycho/social support and network

Time: 3 months

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Description: Ad hoc survey on support network. The answers to the multiple items will be adjusted so higher values indicate higher levels of psychological and social support

Measure: Psycho/social support and network

Time: 6 months

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Description: Ad hoc survey on support network. The answers to the multiple items will be adjusted so higher values indicate higher levels of psychological and social support

Measure: Psycho/social support and network

Time: 12 months

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Description: The Brief Resilience Scale (BRS) is a 6-item self-reported instrument that measures resilience. The range of scores is 6-30. Higher scores indicate higher resilience levels.

Measure: Resilience

Time: Baseline

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Description: The Brief Resilience Scale (BRS) is a 6-item self-reported instrument that measures resilience. The range of scores is 6-30. Higher scores indicate higher resilience levels.

Measure: Resilience

Time: 3 months

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Description: The Brief Resilience Scale (BRS) is a 6-item self-reported instrument that measures resilience. The range of scores is 6-30. Higher scores indicate higher resilience levels.

Measure: Resilience

Time: 6 months

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Description: The Brief Resilience Scale (BRS) is a 6-item self-reported instrument that measures resilience. The range of scores is 6-30. Higher scores indicate higher resilience levels.

Measure: Resilience

Time: 12 months

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Description: The 12-item version of the General Health Questionnaire (GHQ-12) is a self-reported instrument that measures symptoms of anxiety and depression. It provides cut-off points to identify people at risk of anxiety and/or depression, which differ slightly between countries

Measure: Anxiety and depressive symptoms

Time: Baseline

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Description: The 12-item version of the General Health Questionnaire (GHQ-12) is a self-reported instrument that measures symptoms of anxiety and depression. It provides cut-off points to identify people at risk of anxiety and/or depression, which differ slightly between countries

Measure: Anxiety and depressive symptoms

Time: 3 months

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Description: The 12-item version of the General Health Questionnaire (GHQ-12) is a self-reported instrument that measures symptoms of anxiety and depression. It provides cut-off points to identify people at risk of anxiety and/or depression, which differ slightly between countries

Measure: Anxiety and depressive symptoms

Time: 6 months

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Primary Outcomes

Description: The CAPS is a 32-item self-report scale designed to measure perceptual anomalies and hallucinatory experience that has already been validated in clinical and nonclinical populations. Each of the 32 items involves a question related to a specific hallucinatory experience to which the participant can answer 'yes' or 'no'. If the participant answers 'yes' they are asked to rate how distressing, how intrusive and how often the experience occurs on separate 1-5 rated Likert scales. The scale total is calculated as the total number items responded to with 'yes' (possible range 0-32) and the subscale totals are calculated as the total of the subscale items (possible range 0-160)

Measure: Total score of the Cardiff Anomalous Perceptions Scale (CAPS)

Time: inclusion, 1 week after inclusion and 1 month after inclusion

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Secondary Outcomes

Description: Paranoia Scale : this self-report scale is widely used in the assessment of paranoia in the general population. The scale is comprised of a set of 20 items, answered in a Likert-like scale ranging from 1 (never) to 5 (always). Scores can vary between 20 and 100, where higher scores indicate greater paranoid ideation

Measure: Paranoia Scale

Time: inclusion, 1 week after inclusion and 1 month after inclusion

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Primary Outcomes

Description: Significant differences among groups in the mean Perceived Stress Scale (PSS) score, which measures the stress severity perceived by the subjects in the last month. The scale is constituted by 10 items that are self-rated by the subject on a 0-4 Likert scale. The scale minimum total score is 0, the maximum is 40. Higher total scores indicate a worse outcome

Measure: Perceived Stress Scale (PSS) outcome

Time: 10 days

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Secondary Outcomes

Description: Significant differences among groups in the mean Generalized Anxiety Disorder (GAD-7) scale score, which measures anxiety symptoms' severity in the last two weeks. The scale is constituted by 7 items that are self-rated by the subject on a 0-3 Likert scale. The scale minimum total score is 0, the maximum is 21. Higher total scores indicate a worse outcome

Measure: Generalized Anxiety Disorder (GAD-7) scale outcome

Time: 10 days

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Description: Significant differences among groups in the mean Patient Health Questionnaire (PHQ-9) scale score, which measures depressive symptoms' severity in the last two weeks. The scale is constituted by 9 items that are self-rated by the subject on a 0-3 Likert scale. The scale minimum total score is 0, the maximum is 21. Higher total scores indicate a worse outcome

Measure: Patient Health Questionnaire (PHQ-9) scale outcome

Time: 10 days

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Description: Significant differences among groups in the mean Specific Psychotic Experiences Questionnaire (SPEQ) - Paranoia subscale score. The SPEQ scale is designed for the assessment of current sub-threshold psychotic symptoms in multiple domains. The Paranoia subscale measures persecutory/reference ideas and is constituted by 15 items that are self-rated by the subject on a 0-5 Likert scale. The subscale minimum total score is 0, the maximum is 75. Higher total scores indicate a worse outcome

Measure: Specific Psychotic Experiences Questionnaire (SPEQ) - Paranoia subscale outcome

Time: 10 days

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Description: Significant differences among groups in the mean Specific Psychotic Experiences Questionnaire (SPEQ) - Grandiosity subscale score. The Grandiosity subscale measures grandiosity/megalomaniac ideas and is constituted by 8 items that are self-rated by the subject on a 0-3 Likert scale. The subscale minimum total score is 0, the maximum is 24. Higher total scores indicate a worse outcome

Measure: Specific Psychotic Experiences Questionnaire (SPEQ) - Grandiosity subscale outcome

Time: 10 days

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Description: Significant correlations between mean Zarit Burden Interview (ZBI) and mean scores on the Perceived Stress Scale (PSS). The ZBI is designed for the assessment of caregiver burden. The scale is constituted by 22 items that are self-rated by the subject on a 0-4 Likert scale. The scale minimum total score is 0, the maximum is 88. Higher total scores indicate a worse outcome

Measure: Caregiver Burden

Time: 10 days

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Primary Outcomes

Description: total severity score from the Impact of Event Scale-Revised (IES-R)

Measure: impact of the COVID-19 pandemic on psychiatric symptomatology

Time: through study completion, an average of 2 year

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Primary Outcomes

Description: Hospitalization over a one month period. The primary outcome will be collected by a phone call from a medical student to the patient 1 month after randomization date. Hospitalizations (date, location, length, if available, and reason) will be collected. Because there will be many patients to be called for each practitioner, we expect these phone call to occur within a few days after day 28.

Measure: Hospitalization(s) at 1 month

Time: 1 month

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Secondary Outcomes

Description: In the experimental group only: proportion of patients for whom the practitioner had to call back after the medical student had phoned (just after allocation of the practice to the experimental group) at 1 month.

Measure: Phone-call from the general practitioner (in the experimental group only)

Time: 1 month

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Description: Mortality will be reported after checking with the city of the patient's home if there is no response to the phone call

Measure: Mortality at 1 month

Time: 1 month

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Description: Number of general practitioner consultations and teleconsultations (and time of general practitioner consultation, i.e. during the containment period or not) using data from the French Health National (SNDS) Database

Measure: Use of primary care

Time: 6 months

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Description: Number of consultations with another medical specialist (and time of consultation, i.e. during the containment period or not) using data from the French Health National (SNDS) Database

Measure: Use of secondary care

Time: 6 months

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Description: Number of prescriptions related to the chronic disease that were dispensed by the pharmacy using data from the French Health National (SNDS) Database

Measure: Number of prescriptions related to the chronic disease dispensed by the pharmacy

Time: 6 months

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Description: Number of hospitalizations using data from the French Health National (SNDS) Database

Measure: Number of hospitalization(s)

Time: 6 months

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Description: Time to hospitalization using data from the French Health National (SNDS) Database

Measure: Time to hospitalization(s)

Time: 6 months

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Description: Hospitalization duration using data from the French Health National (SNDS) Database

Measure: Hospitalization(s)' durations

Time: 6 months

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Description: Reason for hospitalization using data from the French Health National (SNDS) Database

Measure: Reasons for hospitalization(s)

Time: 6 months

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Description: Number of deaths using data from the French Health National (SNDS) Database

Measure: Mortality at 6 months

Time: 6 months

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Description: Only for patients in the COVIQuest_CV sub-trial: Cardiovascular events (MACE): nonfatal stroke, nonfatal myocardial infarction, cardiovascular death and hospitalization for heart failure using data from the French Health National (SNDS) Database

Measure: Cardiovascular events (MACE)

Time: 6 months

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Description: Only for patients in the COVIQuest_MH sub-trial: Psychotropic drugs consumption using data from the French Health National (SNDS) Database

Measure: Psychotropic drugs

Time: 6 months

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Primary Outcomes

Description: Frequency of central or peripheral neurological or psychiatric symptoms observed in patients with COVID-19

Measure: Central or peripheral neurological symptoms or psychiatric symptoms observed in patients with Covid-19

Time: 12 months

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Secondary Outcomes

Description: Impact on neurological or psychiatric disease trajectories assessed by severity scores or subjective progression (improved, stable, impaired) during and after COVID-19 pathology in patients with pre-existing neurological and psychiatric diseases

Measure: Progression of pre-existing neurological or psychiatric pathologies

Time: 12 months

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Primary Outcomes

Description: Cohen's Perceived Stress Scale (scores ranged from 0 to 40, higher scores indicating worse stress)

Measure: Mental health - Stress

Time: through study completion, estimated to 8 months

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Description: Generalized Anxiety Disorder Scale (scores ranged from 0 to 21, higher scores indicating worse anxiety)

Measure: Mental health - Anxiety

Time: through study completion, estimated to 8 months

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Description: Quick Inventory of Depressive Symptomatology-Self-report, short version (scores ranged from 0 to 27, higher scores indicating worse depression)

Measure: Mental health - Depression

Time: through study completion, estimated to 8 months

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Secondary Outcomes

Description: Measure of Moral Distress - Healthcare Professionals (scores ranged from 0 to 432, higher scores indicating worse moral distress)

Measure: Moral distress in healthcare workers

Time: through study completion, estimated to 8 months

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Description: Rushton Moral Resilience Scale (scores ranged from 1 to 4, higher scores indicating more resiliency)

Measure: Moral resilience in healthcare workers

Time: through study completion, estimated to 8 months

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Description: Frequency of interacting with other people (daily, weekly, monthly, less often than monthly)

Measure: Social life

Time: through study completion, estimated to 8 months

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Description: Fever, Cough, Difficulty breathing or shortness of breath, Tiredness, Aches and pains, Nasal congestion, Runny nose, Sore throat, Diarrhea (Mild Moderate, Severe, N/A)

Measure: COVID-9 symptoms

Time: through study completion, estimated to 8 months

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Description: Mortality (Yes/No): https://datadictionary.ices.on.ca/Applications/DataDictionary/Default.aspx

Measure: Adverse health long-term outcome

Time: 5 years before the outbreak and two years after

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Description: Hospitalizations (total number): https://datadictionary.ices.on.ca/Applications/DataDictionary/Default.aspx

Measure: Health care utilization - Inpatient

Time: 5 years before the outbreak and two years after

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Description: Emergency Department visits (Total number): https://datadictionary.ices.on.ca/Applications/DataDictionary/Default.aspx

Measure: Health care utilization - ER

Time: 5 years before the outbreak and two years after

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Description: Outpatient visits: https://datadictionary.ices.on.ca/Applications/DataDictionary/Default.aspx

Measure: Health care utilization - Outpatient

Time: 5 years before the outbreak and two years after

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Description: Pittsburgh Sleep Quality Index (scores ranged from 0 to 21, higher scores indicating worse sleep disturbances)

Measure: Sleep

Time: through study completion, estimated to 8 months

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Primary Outcomes

Description: number of perception distortions

Measure: number of perception distortions

Time: 1 day

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Secondary Outcomes

Description: Recall number of deaths

Measure: Recall number of deaths

Time: 1 day

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Primary Outcomes

Description: Depression, anxiety and stress scales (DASS21). Score range: 0 (worst outcome) to 21 (best outcome)

Measure: Depression, anxiety and stress

Time: 2 weeks

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Secondary Outcomes

Description: Davidson Trauma Scale (DTS). The DTS is a 17-item, Likert-scale, self-report instrument that assesses the 17 DSM-IV symptoms of PTSD. Both a frequency and a severity score can be determined. The DTS yields a frequency score (ranging from 0 to 68), severity score (ranging from 0 to 68), and total score (ranging from 0 to 136). Higher scores are indicative a worse outcome.

Measure: Post-traumatic stress syndrome

Time: 2 weeks

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Description: Insomnia Severity Index. Score range: 0 (best outcome) to 28 (worst outcome)

Measure: Insomnia

Time: 2 weeks

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Description: General Self-Efficacy Scale. Score range: 10 (worst outcome) to 40 (best outcome)

Measure: Self Efficacy

Time: 2 weeks

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Primary Outcomes

Description: Number of intrusive memories of traumatic events recorded by participants in a daily pen and and paper diary.

Measure: Frequency of intrusive memories

Time: Baseline weeks 1-3, throughout the duration of the intervention phase (approximately 5 weeks), post-intervention weeks 1-2 and for 1 week 2 months post-intervention. Change is assessed from baseline to post-intervention.

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Secondary Outcomes

Description: A brief bespoke measure of concentration adapted from that used previously with refugees (Holmes et al., 2017). It has three questions about disruption to concentration from intrusive memories. A higher score on each question means a worse outcome.

Measure: Concentration

Time: Baseline, 2-weeks post-intervention and 2-months post-intervention

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Description: Developed by Woodfield Trauma Service. The measure asks how many hours the person has spent doing various activities in the past two weeks (for example, domestic chores, exercise, cultural activities). A higher score means a better outcome.

Measure: Social and Occupational Activity Tally (SOAT)

Time: Baseline, 2-weeks post-intervention and 2-months post-intervention

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Description: Four items from the Dissociative Experiences Scale II - items two, three, 14 and 20 (DES II; Carlson, & Putnam, 1993). Each item asks how often (from 0% to 100% of the time) the dissociative experience described happens to the individual. A higher score on each question means a worse outcome.

Measure: Dissociation

Time: Baseline, 2-weeks post-intervention and 2-months post-intervention

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Description: The PCL-5 (Weathers, Litz, Keane, Palmieri, Marx, & Schnurr, 2013) is a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. Total scores can range from 0 to 80, with higher scores meaning a worse outcome.

Measure: Post-Traumatic Stress Disorder (PTSD) Checklist for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (PCL-5)

Time: Baseline and 2-weeks post-intervention

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Description: The PHQ-9 (Kroenke, Spitzer & Williams, 2001) is a nine-item self-report measure that assesses the nine DSM-IV symptoms of depression. Total scores can range from 0 to 27, with higher scores meaning a worse outcome.

Measure: Patient Health Questionnaire (PHQ-9)

Time: Baseline and 2-weeks post-intervention

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Description: The WHO DAS 2.0 (World Health Organisation, 2010) is a measure of health and disability. Total scores can range from 0 to 48, with higher scores meaning a worse outcome.

Measure: World Health Organisation Disability Assessment Schedule 2.0 (WHO DAS 2.0) 12 item version

Time: Baseline and 2-weeks post-intervention

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Other Outcomes

Description: A bespoke measure to assess adherence to self-guided practice of the intervention. It includes four questions to assess how often, and for how long, the person played Tetris after experiencing intrusive memories during the previous week.

Measure: Self-Guided Intervention Adherence Questionnaire

Time: Time Frame: Intervention sessions 2-5, 1 week post-intervention, 2 weeks post-intervention and 2 months post-intervention.

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Description: A bespoke questionnaire to gain feedback on the intervention. It includes 16 questions to assess acceptability and usefulness of the intervention with a variety of response options including yes/no, visual analogue scales and open responses.

Measure: Feedback Questionnaire

Time: 1-week post-intervention.

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Primary Outcomes

Description: Number of intrusive memories of traumatic events recorded by participants in a pen and and paper diary.

Measure: Frequency of intrusive memories

Time: Daily through study completion, an average of 3 months. Change is assessed from baseline to post-intervention.

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Secondary Outcomes

Description: A brief bespoke measure of concentration adapted from that used previously with refugees (Holmes et al., 2017). It has three questions about disruption to concentration from intrusive memories. A higher score on each question means a worse outcome.

Measure: Concentration

Time: Baseline and 2-weeks post-intervention

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Description: Developed by Woodfield Trauma Service. The measure asks how many hours the person has spent doing various activities in the past two weeks (for example, domestic chores, exercise, cultural activities). A higher score means a better outcome.

Measure: Social and Occupational Activity Tally (SOAT)

Time: Baseline and 2-weeks post-intervention

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Description: Four items from the Dissociative Experiences Scale II - items two, three, 14 and 20 (DES II; Carlson, & Putnam, 1993). Each item asks how often (from 0% to 100% of the time) the dissociative experience described happens to the individual. A higher score on each question means a worse outcome.

Measure: Dissociation

Time: Baseline and 2-weeks post-intervention

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Description: The PCL-5 (Weathers, Litz, Keane, Palmieri, Marx, & Schnurr, 2013) is a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. Total scores can range from 0 to 80, with higher scores meaning a worse outcome.

Measure: Post-Traumatic Stress Disorder (PTSD) Checklist for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (PCL-5)

Time: Baseline and 2-weeks post-intervention

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Description: The PHQ-9 (Kroenke, Spitzer & Williams, 2001) is a nine-item self-report measure that assesses the nine DSM-IV symptoms of depression. Total scores can range from 0 to 27, with higher scores meaning a worse outcome.

Measure: Patient Health Questionnaire (PHQ-9)

Time: Baseline and 2-weeks post-intervention

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Description: The WHO DAS 2.0 (World Health Organisation, 2010) is a measure of health and disability. Total scores can range from 0 to 48, with higher scores meaning a worse outcome.

Measure: World Health Organisation Disability Assessment Schedule 2.0 (WHO DAS 2.0) 12 item version

Time: Baseline and 2-weeks post-intervention

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Other Outcomes

Description: A bespoke measure to assess adherence to self-guided practice of the intervention. It includes four questions to assess how often, and for how long, the person played Tetris after experiencing intrusive memories during the previous week.

Measure: Self-Guided Intervention Adherence Questionnaire

Time: Intervention weeks 2-5, 1 week post-intervention and 2 weeks post-intervention

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Description: A bespoke questionnaire to gain feedback on the intervention. It includes 16 questions to assess acceptability and usefulness of the intervention with a variety of response options including yes/no, visual analogue scales and open responses.

Measure: Feedback Questionnaire

Time: 1-week post-intervention.

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Primary Outcomes

Description: The Impact of Event Scale - Revised (IES-R). IES-R is a 22-item scale with possible scores ranging from 0 - 88. Scores higher than 24 are of concern indicating possible health and well-being consequences.

Measure: Emotional Impact

Time: 7 days

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Secondary Outcomes

Description: Patient Health Questionaire (PHQ-9). The PHQ-9 has a range from 0 - 27. PHQ-9 scores of 5, 10, 15, and 20 represents mild, moderate, moderately severe and severe depression.

Measure: Depression

Time: 2 weeks

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Description: Generalized Anxiety Disorder 7-item (GAD-7). Scores range from 0 - 21. When screening for anxiety disorders, a score of 8 or greater represents a reasonable cut-point for identifying probable cases of generalized anxiety disorder.

Measure: Anxiety

Time: 2 weeks

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Description: The ISI7 is a 7-item instrument designed to assess the nature, severity, and impact of insomnia in adults. Scores range from 0 - 28. Higher scores indicate increased likelihood of sleep disturbances.

Measure: Insomnia

Time: 1 week

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Description: Brief Resilience Scale (BRS) is a 6-item scale with scores ranging from 6-30 with higher scores indicating greater resilience.

Measure: Resilience

Time: 2 Weeks

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Description: The Crisis Support Scale (CSS) is a 7-item instrument developed to measure received social support. Scores range from 7 - 98, with higher scores correlating with increased social support.

Measure: Crisis Support Scale

Time: 2 weeks

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Primary Outcomes

Description: Brief Symptom Inventory-18 with higher scores meaning a worse outcome (more depression, anxiety and somatization); Each item is weighted on a 0-4 interval scale; Minimum = 0, Maximum = 72)

Measure: Global symptom load (Anxiety, Somatisation, Depression, Global Symptom Index)

Time: 1 year

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Description: Beck Depression Inventory-II with higher scores mean a worse Outcome (more depressive Symptoms; each item is weighted on a 0-3 interval scale; Minimum = 0, Maximum = 63)

Measure: Depressive symptoms

Time: 1 year

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Description: Pittsburgh Sleep Quality Index (PSQI) with higher scores mean a worse Outcome (more sleeping disturbances; Each item is weighted on a 0-3 interval scale; Minimum = 0, Maximum = 63)

Measure: Sleep disorders and Sleep Quality

Time: 1 year

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Secondary Outcomes

Description: Lifestyle Questions including physical activity, eating behavior, substance use, smoking

Measure: Life style changes

Time: 1 year

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Description: Food Craving Inventory (FCI) with higher scores mean a worse Outcome (more Food craving; Each item is weighted on a 0-4 interval scale; Minimum = 0, Maximum = 112)

Measure: Food Craving

Time: 1 year

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Description: COVID-19 questionnaire with higher scores meaning a worse Outcome (more fears and negative emotions; each item is weighted on a 0-10 interval scale)

Measure: COVID-19 associated fears and emotional responses to the pandemic

Time: 1 year

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Primary Outcomes

Description: COVID-19's Patients mortality all cause: incidence proportion.

Measure: Mortality

Time: 12 months.

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Description: COVID-19's Patients suicide: incidence proportion.

Measure: Mortality-suicide

Time: 12 months.

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Secondary Outcomes

Description: In-hospital COVID-19's Patients oxygen invasive ventilation or high flow oxygen devices :incidence proportion of Brescia COVID-19 respiratory Severity Scale Index (Levels 0-3 worse outcome) cutoff Level ≥ 2 -

Measure: Incidence of hospitalization for respiratory failure of COVID-19's Patients-

Time: 1 months.

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Description: Homecare interventions for anxiety and depression requiring drugs treatment: incidence proportion.

Measure: Incidence of al home professional psychiatric-psychological interventions for mental disorder.

Time: 12 months.

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Description: Scoring system for depression and anxiety requiring drugs treatment: incidence proportion of BDI-II aggregate components score 0- 63 ( worse outcome) , cutoff > 29.

Measure: Incidence of mental disorder: Beck Depression Inventory-Second Edition (BDI-II).

Time: 12 months.

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Description: Scoring system for sleep disorders requiring drugs treatment: incidence proportion of aggregate PSQI score 0-21 (worse outcome) , cutoff > 8.

Measure: Incidence od spleep disorder:Pittsburgh Sleep Quality Index (PSQI).

Time: 12 months.

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Primary Outcomes

Description: Number of hospitalized patients From March 12th to April 09th

Measure: Number of hospitalized patients

Time: 1 months

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Secondary Outcomes

Description: Primary psychiatric diagnostic From March 12th to April 09th

Measure: Cause of hospitalization

Time: 1 months

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Other Outcomes

Description: Patients without psychiatric antecedent (number) From March 12th to April 09th

Measure: Lengh of hospitalization

Time: 1 months

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Description: Presence of absence of history of treatment interruption leading to the hospitalization From March 12th to April 09th

Measure: Treatment interruption

Time: 1 months

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Description: Number of hospitalized patients living alone (opposed to those living with family) From March 12th to April 09th

Measure: Number of hospitalized patients living alone

Time: 1 months

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Description: Number of patients using drugs From March 12th to April 09th

Measure: Use of drugs

Time: 1 months

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Primary Outcomes

Description: Recovery Assesment Scale (RAS). This is a 24-item questionnaire with 5-point Likert scales (1-2-3-4-5). Higher scores are positively correlated with higher levels of recovery. Minimum score = 24 : maximum score = 120.

Measure: Assessment of patients' current status : recovery (personal recovery)

Time: 12 weeks

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Description: Participating patients will fill out the Citizenship Measure (CM). This is a 23-item questionnaire with 5-point Likert scales (1-2-3-4-5). Higher scores are positively correlated with higher levels of citizenship. Minimum score = 23 : maximum score = 115.

Measure: Assessment of patients' current status : citizenship (personal recovery)

Time: 12 weeks

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Description: Participating with 5-point Likert scales (0-1-2-3-4). Higher scores are positively correlated with higher levels of COVID-related levels of stress. Minimum score = 0 : maximum score = 144.

Measure: Assessment of patients' current status : COVID-19 Stress Scales

Time: 12 weeks

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Secondary Outcomes

Description: Participating patients will fill out the Anxiety State-Trait Anxiety Inventory Form Y6 (STAI-Y6). This is a 6-item questionnaire with 4-point Likert scales (1-2-3-4). Higher scores are positively correlated with higher levels of anxiety. Minimum score = 6 : maximum score = 24.

Measure: Assessment of patients' current status : anxiety (clinical recovery)

Time: 12 weeks

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Description: Participating patients will fill out the Depression Patient Health Questionnaire (PHQ-9). This is a 9-item questionnaire with 4-point Likert scales (0-1-2-3). Higher scores are positively correlated with higher levels of depression. Minimum score = 0 : maximum score = 27.

Measure: Assessment of patients' current status : depression (clinical recovery)

Time: 12 weeks

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Description: Participating patients will fill out the Alcohol Use Disorders Identification Test (AUDIT-10). This is a 10-item questionnaire with 5-point Likert scales (0-1-2-3-4). Higher scores are positively correlated with higher levels of alcohol dependence. Minimum score = 0 : maximum score = 40.

Measure: Assessment of patients' current status : alcohol dependence (clinical recovery)

Time: 12 weeks

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Description: Participating patients will fill out the Drug Abuse Screening Test (DAST-10). This is a 10-item questionnaire with noyes answers (0-1). Higher scores are positively correlated with higher levels of drog dependence. Minimum score = 0 : maximum score = 10.

Measure: Assessment of patients' current status : drug dependence (clinical recovery)

Time: 12 weeks

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Description: Psychosis Screening Questionnaire (PSQ 12 items) with no-unsure-yes answers (1-2-3). Higher scores are positively correlated with higher levels of psychosis. Minimum score = 12 : maximum score = 36.

Measure: Assessment of patients' current status : psychosis (clinical recovery)

Time: 12 weeks

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Description: Participating patients will fill out the World Health Organization Disability Assessment Schedule (WHODAS 2.0). This is a 12-item questionnaire with 5-point Likert scales (0-1-2-3-4). Lower scores are positively correlated with higher levels of social functioning. Minimum score = 0 : maximum score = 48.

Measure: Assessment of patients' current status : social functioning (clinical recovery)

Time: 12 weeks

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Primary Outcomes

Description: Quantitative online questionnaire Survey using UniPark

Measure: Interest in digital interventions (attitudes, behavioral intentions, behavioral experiences)

Time: T1 (prior/beginning of rehab/clinic stay); T2 (end of rehab/clinic stay approx. 5 weeks after T1)

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Description: Quantitative online questionnaire Survey using UniPark

Measure: Usability and effectiveness of digital interventions

Time: T1 (prior/beginning of rehab/clinic stay); T2 (end of rehab/clinic stay approx. 5 weeks after T1)

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Description: Quantitative online questionnaire Survey using UniPark

Measure: Stressors and barriers due to Covid-19

Time: T1 (prior/beginning of rehab/clinic stay); T2 (end of rehab/clinic stay approx. 5 weeks after T1)

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Primary Outcomes

Description: Feasibility will be determined by the following measures: Able to recruit >30% of eligible patients approached Complete early EMDR intervention programme in 75% or more of trial participants randomised to intervention. Protocol adherence Assignment of causality of serious events will be assessed by the chief investigator. Events attributable to trial procedures will be reviewed by trial management board, study sponsor and the research ethics committee, in order to determine ongoing feasibility. Outcome measures completed in 75% or more of trial participants

Measure: Feasibility of recruitment, intervention adherence, incidence of treatment related adverse events and trial completion to final assessment timepoints

Time: 12 months

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Secondary Outcomes

Description: The PTSD Checklist-Civilian Version (PCL-C) is a validated, standardised self-reporting questionnaire for PTSD comprising of 17 items that correspond to key PTSD symptoms

Measure: Post-Traumatic stress disorder

Time: 6 months post-hospital discharge

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Description: Hospital Anxiety and Depression Scale (HADS) is a 14-item, self-reported measure with 7-items relating to symptoms of anxiety and 7-items relating to depression

Measure: Anxiety and depression

Time: 6 months

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Description: Montreal Cognitive Assessment (MoCA) is a validated tool, used to detect cogntive impairment

Measure: Cognitive function

Time: 6 months post-hospital discharge

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Description: EQ5D -5L comprises five quality-of-life dimensions; mobility, self-care, usual activities, pain/discomfort andanxiety/depression.

Measure: Health Related Quality of Life

Time: 6 months post-hospital discharge

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Description: WHODAS 2.0 is a generic assessment tool that produces standarised disability levels and profiles

Measure: Health and disability

Time: 6 months post-hospital discharge

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Description: Wrist worn physical activity monitoring

Measure: Physical activity

Time: 6 months post-hospital discharge

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Description: Patient generated subjective global assessment

Measure: Nutritional status

Time: 6 months post-hospital discharge

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Primary Outcomes

Measure: Percentage of Participants with Adverse Events in Part 1

Time: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort)

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Measure: Percentage of Participants with Adverse Events in Part 2

Time: From randomization up to 8 weeks

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Measure: Part 2: Change in suicide risk assessed using the Columbia Suicide Severity Rating Scale (C-SSRS)

Time: From randomization up to 8 weeks

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Secondary Outcomes

Measure: Part 1: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

Time: Day 1

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Measure: Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

Time: Day 1

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Measure: Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Terminal Elimination Phase Half-Life (T1/2) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Area Under the Concentration-Time Curve from Time 0 to 12 hours (AUC(0-12h)) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Area Under the Concentration-Time Curve from Time Extrapolated to Infinity (AUC (0-inf)) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Apparent Clearance (CL/F) of RO6953958 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Apparent Volume of Distribution (V/F) of RO6953958 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Cumulative Amount of Unchanged Drug Excreted into the Urine (Ae) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Fraction of the Administered Drug Excreted into the Urine (Fe) of RO6953958 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Part 1: Renal Clearance of the Drug from Urine (CLR) of RO6953958 in Fasted and Fed state

Time: Day 1 to Day 5

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Measure: Parts 2: Cmax of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 and Day 10

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Measure: Parts 2: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Cmax of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 and Day 10

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Measure: Parts 2: Average Plasma Concentration (Cavg) of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 to Day 14

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Measure: Part 2: Tmax of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 and Day 10

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Measure: Part 2: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 to Day 14

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Measure: Part 2: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 to Day 14

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Measure: Part 2: T1/2 of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 to Day 14

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Measure: Part 2: CL/F of RO6953958

Time: Day 1 to Day 14

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Measure: Part 2: V/F of RO6953958

Time: Day 1 to Day 14

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Measure: Part 2: Ae of RO6953958

Time: Day 1 to Day 14

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Measure: Part 2: Fe of RO6953958

Time: Day 1 to Day 14

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Measure: Part 2: CLR of RO6953958

Time: Day 1 to Day 14

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Measure: Part 2: Trough Plasma Concentration (Ctrough) of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 to Day 14

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Measure: Part 2: Accumulation Ratio based on AUC (Rauc) of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 to Day 14

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Measure: Part 2: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 to Day 14

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Measure: Part 2: Accumulation Ratio based on Ctrough (RCtrough) of RO6953958 and its Metabolites RO7021594 and RO7045755

Time: Day 1 to Day 14

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Primary Outcomes

Description: measure of psychological and psychiatric difficulties in connection with the pandemic and confinement. This will allow a rapid implementation of a course of care adapted and specific to the difficulties presented by each child, by Quantitative and qualitative assessments :

Measure: diagnosis of possible psychological and psychiatric difficulties at baseline

Time: at baseline Day 0

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Secondary Outcomes

Description: measure of psychological and psychiatric difficulties in connection with the pandemic and confinement. This will allow a rapid implementation of a course of care adapted and specific to the difficulties presented by each child, by Quantitative and qualitative assessments

Measure: follow up of psychological and psychiatric difficulties at V2

Time: at one month after baseline

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Description: measure of psychological and psychiatric difficulties in connection with the pandemic and confinement. This will allow a rapid implementation of a course of care adapted and specific to the difficulties presented by each child, by Quantitative and qualitative assessments

Measure: follow up of psychological and psychiatric difficulties at V3

Time: at one week after the end of the containment

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Description: measure of psychological and psychiatric difficulties in connection with the pandemic and confinement. This will allow a rapid implementation of a course of care adapted and specific to the difficulties presented by each child, by Quantitative and qualitative assessments

Measure: follow up of psychological and psychiatric difficulties at V4

Time: at one month after the end of the containment

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Description: measure by Post-Traumatic Stress Disorder (PTSD) scale: The frequency and intensity of PTSD symptoms will be assessed using the Young Child PTSD Checklist (YCP) for children aged 3 months to 6 years and 11 months; or the Child PTSD checklist (CPC) for children aged 7 years to 17 years and 11 months ; or with the Post-Traumatic Stress Disorder ( PTSD) checklist 5 (PCL 5 ) for adults

Measure: impact of traumatic history prior to confinement

Time: at one week after baseline and at one month after the end of the containment

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Description: measure by Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS): This is a semi-directed interview for children over the age of 7. It is done by interviewing the parent and the child. The interview covers both current issues.

Measure: impact of other previous psychiatric disorders

Time: at one month after baseline and at one month after the end of the containment

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Description: measure by Parenting stress index-short form (PSI-SF) that measures the extent of parental stress, as well as stress in the relationship between parent and child, and parents' difficulties in the day-to-day management of children.

Measure: parental reaction

Time: at one week after baseline and at one week after the end of the containment

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Primary Outcomes

Description: It will be assessed with the 4-item version of the PTSD checklist for DSM-5 (PCL-5), which evaluates the presence and severity of 4 DSM-5 Criteria symptoms of PTSD over the past month (0 = not at all to 4 = extremely) and has been shown to generate diagnoses that closely parallel those of the full PCL-5 (AUC>0.9), making it well-suited for screening. The Spanish version is available.

Measure: Post-traumatic stress disorder

Time: 6 months

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Description: It will be evaluated with the Patient Health Questionnaire 8-item version (PHQ-8) with a 2-week recall period. Items have four response categories on frequency of the symptom that can be summed up to obtain a severity score, with cut-points of 5, 10, and 15 representing mild, moderate, and severe levels of depression, respectively, showing good diagnostic accuracy for depressive disorder (AUC>0.90) and high reliability (>0.8).

Measure: Depression

Time: 6 months

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Description: It will be screened with the seven-item Generalized Anxiety Disorder scale (GAD-7). Cut-points of 5, 10, and 15 represent mild, moderate, and severe levels of anxiety, respectively, with AUC>0.8 for the detection of anxiety. The Spanish versions of the PHQ and GAD-7 have been developed (https://www.phqscreeners.com).

Measure: Generalized Anxiety Disorder

Time: 6 months

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Description: It will be evaluated with a modified version of the Columbia Suicide Severity Rating Scale, including passive suicidal ideation ("wish you were dead or would go to sleep and never wake up"), active suicidal ideation ("have thoughts of killing yourself"), suicide plans ("think about how you might kill yourself [e.g., taking pills, shooting yourself] or work out a plan of how to kill yourself"), and suicide attempt ("make a suicide attempt [i.e., purposefully hurt yourself with at least some intent to die]).It has been translated into Spanish showing good discrimination ability for suicidal behavior.

Measure: Suicidal thoughts and behaviors

Time: 6 months

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Secondary Outcomes

Description: It will be evaluated with the CAGE questionnaire, that consists of 4 items focusing on Cutting down, Annoyance by criticism, Guilty feeling, and Eye-openers and have proved useful in helping to make a diagnosis of alcoholism.Item responses on the CAGE questions are scored 0 for "no" and 1 for "yes" answers, with a higher score being an indication of alcohol problems. A total score of two or greater is considered clinically significant. The questionnaire has been adapted into Spanish.

Measure: Alcohol and drug use problems

Time: 6 months

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Description: It will be assessed with item taken and adapted from the CIDI Screening Scales("Panic or anxiety attacks are sudden, strong feelings of fear or anxiety that reach their peak within a few minutes and are usually accompanied by physical reactions like racing heart, sweating, shortness of breath, feeling faint, or feeling sick to your stomach. People who have panic attacks sometimes feel like they might lose control, go crazy, or suddenly die. With this definition in mind, about how many panic attacks did you have since the onset of COVID-19 outbreak?")

Measure: Panic attacks

Time: 6 months

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Description: It will be assessed with the 5-level version of the EQ-5D-5L, for which a Spanish version is available showing good validity.

Measure: Health-related Quality of Life

Time: 6 months

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Description: It will be evaluated with a single item assessing general health, ''In general, how would you rate your health'' with response options of ''excellent, very good, good, fair, or poor''), which has shown to have a strong association with negative health outcomes, including mortality [10.1111/j.1525-1497.2005.0291.x]. The Spanish version of the item has provided similar results .

Measure: Overall Perceived Health

Time: 6 months

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Description: It will be assessed using an adapted version of the Sheehan Disability Scale that assessed impairment separately in each of four role domains: home management/chores, work roles, close personal relationships, and social life.

Measure: Role limitation

Time: 6 months

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