Enhancing COVID Rehabilitation with Technology (ECORT): Protocol for an open-label, single site randomized controlled trial evaluating the effectiveness of electronic case management for individuals with persistent COVID-19 symptoms.

Enhancing COVID Rehabilitation with Technology (ECORT): Protocol for an open-label, single site randomized controlled trial evaluating the effectiveness of electronic case management for individuals with persistent COVID-19 symptoms. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Enhancing COVID Rehabilitation with Technology (ECORT): Protocol for an open-label, single site randomized controlled trial evaluating the effectiveness of electronic case management for individuals with persistent COVID-19 symptoms. Simon Hatcher, Joel Werier, Nicole E Edgar, James Booth, William J Cameron, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1723719/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Background : As of May 2022, Ontario has seen more than 1.3 million cases of COVID-19. While the majority of individuals will recover from infection within four weeks, a significant subset experience persistent and often debilitating symptoms, known as “post-COVID syndrome” or “Long COVID”. Those with Long COVID experience a wide array of symptoms, with variable severity, including fatigue, cognitive impairment, and shortness of breath. Further, the prevalence and duration of Long COVID is unclear, nor is there evidence on the best course of rehabilitation for individuals to return to their desired level of function. Previous work with chronic conditions has suggested that the addition of electronic case management (ECM) may help to improve outcomes. These platforms provide enhanced connection with care providers, detailed symptom tracking and goal setting, and access to relevant resources. In this study, our primary aim is to determine if the addition of ECM with health coaching improves Long COVID outcomes at three months compared to health coaching alone. Methods : The trial is an open-label, single site, randomized controlled trial of ECM with health coaching (ECM+) compared to health coaching alone (HC). Both groups will continue to receive usual care. Participants will be randomized equally to receive health coaching (+/- ECM) for a period of 8 weeks and a 12-week follow-up. Our primary outcome is the WHO Disability Assessment Scale (WHODAS), 36-item self-report total score. Participants will also complete measures of cognition, fatigue, breathlessness, and mental health. Participants and care providers will be asked to complete a brief qualitative interview at the end of the study to evaluate acceptability and implementation of the intervention. Discussion : There is currently little evidence about the optimal treatment of Long COVID patients or the use of digital health platforms in this population. The results of this trial could result in rapid, scalable, and personalized care for people with Long COVID which will decrease morbidity after an acute infection. Results from this study will also inform decision making in Long COVID and treatment guidelines at provincial and national levels. Trial registration : ClinicalTrials.gov, NCT05019963, Registered on 25 August 2021, https://clinicaltrials.gov/ct2/show/NCT05019963 COVID-19 SARS-CoV-2 Long-COVID Post-COVID rehabilitation Blended Care Electronic Case Management Figures Figure 1 Administrative information Note: The numbers in curly brackets in this protocol refer to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist item numbers. The order of the items has been modified to group similar items (see http://www.equator-network.org/reporting-guidelines/spirit-2013-statement-defining-standardprotocol-items-for-clinical-trials/). Title {1} Enhancing COVID Rehabilitation with Technology (ECORT): An open-label, single site randomized controlled trial evaluating the effectiveness of electronic case management for individuals with persistent COVID-19 symptoms. Trial registration {2a and 2b}. ClinicalTrials.gov NCT05019963 Protocol version {3} Version 23 Feb 2022 Funding {4} This study is funded by the Canadian Institutes of Health Research (CIHR). The funders have no role in the design or conduct of the study or the decision to publish results. Author details {5a} (1) Clinical Epidemiology Program, Ottawa Hospital Research Institute (2) Department of Psychiatry, University of Ottawa (3) Department of Mental Health, The Ottawa Hospital, (4) Department of Surgery, The Ottawa Hospital (5) Ontario Workers Network, The Ottawa Hospital (6) No affiliation (7) Division of Infectious Disease, University of Ottawa (8) School of Epidemiology and Public Health, University of Ottawa (9) Department of Medicine, University of Ottawa (10) Centre of Infection, Immunity, and Inflammation, University of Ottawa (11) Department of Pharmacy, The Ottawa Hospital (12) School of Pharmaceutical Sciences, University of Ottawa (13) Division of Physical Medicine and Rehabilitation, University of Ottawa (14) Bruyere Research Institute (15) Parkinson’s Disease and Movement Disorders Center, Division of Neurology, Department of Medicine, The Ottawa Hospital (16) Neuroscience Program, Ottawa Hospital Research Institute (17) University of Ottawa Brain and Mind Institute (18) Department of Psychology, The Ottawa Hospital (19) School of Psychology, University of Ottawa (20) Public Health Agency of Canada (21) Department of Medicine, The Ottawa Hospital (22) Department of Biochemistry, Microbiology and Immunology, University of Ottawa Name and contact information for the trial sponsor {5b} Trial Sponsor: Ottawa Hospital Research Institute (OHRI) Contact name: Dr. Duncan Stewart Address: 501 Smyth Road, Ottawa, ON K1H 8L6 Telephone: (613) 798-5555, ext.79017 Email: [email protected] Role of sponsor {5c} The sponsor (OHRI) had no role in the design of this study and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results. Introduction Background and rationale {6a} In March 2020, the World Health Organization (WHO) declared the novel coronavirus (COVID-19) a global pandemic. At the time of writing this protocol in February 2022, Ontario had confirmed more than 628,000 cases of SARS-CoV-2 since testing began. Most recently, estimates in May 2022 show this number has climbed to 1.3 million cases.(1) For most of these patients, symptoms resolve within 4 weeks of onset. However, it is becoming apparent that a significant subset of infected patients are experiencing symptoms that persist long after the typical course of acute viral infection. These individuals experience a wide constellation of symptoms, with variable intensity over time and often varying from initial acute presentation.(2–6) Currently, the prevalence and duration is unclear, nor is there evidence on the best course of rehabilitation for individuals to return to their desired level of function. 1.1 What is post-COVID syndrome ? The National Institute for Healthcare and Excellence (NICE) defines two distinct groups: ongoing symptomatic COVID (symptoms for 4-12 weeks) and post-COVID syndrome, which describes those with ongoing symptoms, not better explained by another diagnosis, for 12 weeks and longer.(7) The most common symptom experienced is persistent fatigue, followed by dyspnea, cognitive issues such as “brain fog” and cardiothoracic issues. (2,5,6,8) Other symptoms include headaches, muscle and joint pain, persistent cough and psychiatric conditions. (2,6,8,9) An early study found that nearly half of the sample had also experienced a decrease in their quality of life.(6) It is unclear who is most at risk for developing post-COVID syndrome. While severe illness or long time to acute recovery is predictably associated with poor long term outcomes, more than 35% of individuals with mild illness failed to return to baseline health status.(10) Women(2,4) and ethnic minorities (11) may also be at higher risk. Previous research from the SARS pandemic also suggests that social disadvantage, such as job loss or social stigma, were also risk factors for long-term symptoms.(12) The heterogeneous nature of symptoms and risk factors suggest that an “organ-based” or classification approach will not provide optimal outcomes for these patients. An integrated model for rehabilitation, including interdisciplinary care, enhanced case management and screening tools, should be examined.(13,14) 1.1.1 Nomenclature There are at least four terms employed to describe persistent COVID symptoms, including “Long COVID”, “COVID-19 syndrome”, “post COVID-19 syndrome” or “post-acute sequelae of SARS- CoV-2 infection”.(2) We have chosen to refer to the condition as Long COVID as this seems to be the term most preferred by patients.(15) 1.2 Case Management in COVID-19 Rehabilitation Previous work with chronic conditions has suggested that using digital health platforms can improve outcomes.(16,17) These platforms usually have a patient facing app and a clinician facing dashboard and allow personalization of information and resources to the user; the tracking of symptoms, often assisted by the smartphone’s biometric sensors; contain educational resources; allow for goal setting and monitoring; facilitate collaborative care; and, create a connection between the patient and their clinician.(18) Although the size of the effect varies by condition and intervention(16,17), these platforms are often low burden to disseminate and adaptable to individual schedules, and may increase access to specialized care to patients across rural and remote regions. Despite the explosion in e-health and coaching platforms available, a recent systematic review found there were few high quality trials examining the effectiveness of the intervention or its individual components.(19) These platforms have been used across multiple disorders including diabetes(20–22), mental health(23–25) and cancer recovery.(26,27) These e-health platforms also offer the opportunity for improved communication between the patient, caregivers and care providers, increasing both understanding of and adherence to treatment protocols.(18,25,28,29) In the case of Long COVID, the addition of a case management platform may prove particularly beneficial. As information is changing rapidly, patients may have more questions about their health concerns and their treatment plan. With electronic case management, clinicians can readily push new resources and information to patients and offer caregivers a more meaningful role. 1.3 Rationale The most comprehensive relevant guideline regarding Long COVID is the NICE “COVID-19 rapid guideline; managing the long-term effects of COVID-19” published in December 2020.(7) The guideline made key recommendations for research including “What is the clinical effectiveness of different service models of multimodality/multidisciplinary post-COVID-19 syndrome rehabilitation in improving patient-reported outcomes (such as quality of life)”. The NICE guideline also recommended that patients use symptom diaries or a tracking app to monitor their goals, recovery and any changes in their symptoms. This proposal directly addresses this recommendation, as the NICE guidelines provide no research to support this approach.(7) We aim to utilize these recommendations to evaluate what possible service models incorporating electronic case management (ECM) will improve outcomes in this population. Objectives {7} Primary Objective The primary objective of this trial is to determine if adding ECM with health coaching to usual care improves participant quality of life after three months for patients who present to hospital outpatient clinics experiencing Long COVID. We hypothesize that adding ECM with health coaching to usual care will improve outcomes at three months compared to usual care alone. Secondary Objectives The key secondary objectives of this study are to determine: 1) the cost-effectiveness of adding ECM to usual care for Long COVID patients; 2) what factors predict outcomes at 3 months in patients with Long COVID; 3) if the addition of ECM affects Long COVID symptoms; and 4) how a personalized rehabilitation program supported by a digital platform could be implemented for individuals with Long COVID. We hypothesize that adding ECM to usual care will be cost-effective from a public-payer’s perspective. We also hypothesize that people with Long COVID who had severe acute COVID infections, or adverse childhood experiences or recent negative life events, or a strong sense of injustice at baseline will have poorer outcomes at 3 months. Lastly, we hypothesize that those with ECM will show more improvement across outcome measures at 12 weeks. Following the Medical Research Council guidance on developing and evaluating complex interventions (30) we will conduct a process evaluation guided by the RE-AIM implementation framework.(31) Trial design {8} The proposed study is a 12-month open label, parallel group, randomized controlled trial. Participants will be allocated 1:1 into either electronic case management (ECM) with health coaching plus usual care or health coaching plus usual care alone. Due to the nature of the of the intervention, it will not be possible to blind clinicians or patients to the allocation. Methods: Participants, interventions and outcomes Study setting {9} This single-site study will be conducted at the Ottawa Hospital Research Institute (OHRI). Recruitment will occur through two different streams to increase the diversity of participants. The first stream is a clinic that sees Ontario workers who were infected by SARS-CoV-2 at their worksite, who have made a claim to the Ontario Workplace Safety and Insurance Board (WSIB) and are assessed by the Ontario Workers Network (OWN) based at The Ottawa Hospital (TOH). The second stream are clinics within TOH which are seeing patients with Long COVID. These are clinics specifically for people with Long COVID, for example within the rehabilitation service, or specialist clinics that are seeing people with Long COVID such as respirology, infectious diseases or psychiatry. Eligibility criteria {10} Participants will be recruited from TOH. Participants will be approached by an individual in their circle of care if they meet the eligibility criteria outlined in Table 1. Table 1. Eligibility Criteria Inclusion Criteria Participants must: 1. Be 18 years of age or older 2. Have a confirmed diagnosis of COVID-19 with a PCR test at least 12 weeks prior OR a confirmed Rapid Antigen Test at least 12-weeks prior OR meet Ottawa Public Health guidance for a suspected COVID-19 case (Table 2) 3. Have at least one ongoing symptom consistent with Long COVID as measured by the WHO Post COVID Case Report Form (CRF) 4. Have a minimum WHO Disability Assessment Scale (WHODAS) self-report (36 item) sum score of 15 5. Be willing to use email for study activities 6. Be able and willing to use an electronic platform, either on smartphone or computer web browser, for the duration of the trial 7. Be able to read and understand English or French. 8. Be willing and able to provide informed consent. Exclusion Criteria Participants must not: 1. Have any significant functional impairment (for example. advanced dementia, heart or lung disease) as judged by the assessing clinician 2. Participate in another long-COVID trial where treatment is required in the protocol (pharmacological or behavioural). Observational studies will be allowed. 3. Have symptoms consistent with Long COVID that are better explained by an alternative diagnosis COVID-19 Testing Eligibility Effective December 30 th , 2021 the government of Ontario significantly restricted the eligibility for PCR testing. The general public is no longer eligible for symptomatic PCR testing ( https://news.ontario.ca/en/backgrounder/1001387/updated-eligibility-for-pcr-testing-and-case-and-contact-management-guidance-in-ontario ). Rapid Antigen Tests (RAT) are also significantly limited in Ontario and these results are not officially reported to any health agency. Additionally, in early 2020 testing was unavailable or highly limited. A previously approved, but not implemented, version of this protocol limited eligibility to PCR test only. To ensure that we are able to enroll individuals, inclusion criteria for testing will not be limited to PCR. The preferred confirmation of eligibility will remain a PCR test 12 weeks prior. Second line of eligibility confirmation will be a positive RAT 12 weeks prior. Third line will be for the participant to confirm a suspected case of COVID-19 indicating they were experiencing symptoms at least 12 weeks prior. Determination of a suspected case will follow the Ottawa Public Health Guidelines ( https://www.ottawapublichealth.ca/en/public-health-topics/resources/Documents/Self-Isolation-Flowchart_EN.pdf ) summarized in Table 2. Table 2. Suspected COVID-19 Eligibility Criteria If you experienced one of: If you experienced two or more of: Fever/Chills Cough Shortness of Breath Decrease/Loss of Smell or Taste Sore Throat Headache Runny Nose/Nasal Congestion Extreme Fatigue Muscle/Joint Pains GI Symptoms (Vomiting, Diarrhea) Potential Participants will be asked to confirm that symptoms were a minimum of twelve weeks ago and the delegated research staff will document the date and the list of symptoms experienced. The Principal Investigator will then make the final determination about inclusion in the study. Access to Technology Participants are not required to have a smartphone with a data plan in order to participate in the intervention arm. Participants will be able to access their patient dashboard from their computer or tablet with internet access. Participants who do not have any available options to access the platform and are randomized to the intervention arm will be provided with one pre-paid smartphone with voice and data services for the duration of their study participation. Provision of a second phone in the event of loss or theft will be evaluated on a case-by-case basis. Who will take informed consent? {26a} All informed consent discussions will be completed by a site-delegated study staff member, such as a research coordinator or research assistant. Additional consent provisions for collection and use of participant data and biological specimens {26b} As per Institutional guidelines, participants will be asked to complete a “Consent to Communicate by Email” form prior to completing the informed consent discussion. Participants will be asked permission to share their de-identified trial data in an open access database, in line with Canadian Institutes of Health Research (CIHR) best practice. This trial does not involve collecting biological specimens for storage. Interventions Explanation for the choice of comparators {6b} Utilizing the NICE COVID-19 treatment guideline, we have selected a comparator group that will be able to answer the question “What is the clinical effectiveness of different service models of multimodality/multidisciplinary post-COVID-19 syndrome rehabilitation in improving patient-reported outcomes (such as quality of life)”. The comparator group will receive usual care and health coaching as required. We chose to compare this to health coaching plus electronic case management in the intervention group as this addresses one of the recommended research questions in the NICE guidelines “ What is the clinical effectiveness of different service models of multimodality/multidisciplinary post‑COVID‑19 syndrome rehabilitation in improving patient‑reported outcomes (such as quality of life)?” . Intervention description {11a} Control Arm: Health Coaching Plus Usual Care Assessment. Participants randomized to the control arm will be offered assessment by a clinician, guided by the WHO Post COVID-19 CRF ( https://www.who.int/publications/i/item/global-covid-19-clinical-platform-case-report-form-(crf)-for-post-covid-conditions-(post-covid-19-crf-) . This is a clinical tool developed by the WHO to guide and document the sequelae of COVID-19 and to ensure that clinical and rehabilitation needs are identified. Investigation. Clinician judgement will be used to decide on further testing needed for clinical care. Management. Control participants will receive a rehabilitation plan developed with their health professional that will be implemented in the eight weeks after their initial consultation (baseline visit) and access to a personal health coach. The implementation will involve face to face or virtual care from a registered health professional provided by the clinic or research staff. This may be a combination of, but not limited to, occupational therapy, physical therapy and/or social work/counselling services. The frequency of treatment visits will depend on the individual treatment plan after assessment. All participants will receive access to a health coach. Experimental Arm: Electronic Case Management Plus Usual Care Participants randomized to the experimental arm will receive assessment, investigation and management as outlined in 3.4.1 (Control) plus access to an electronic case management platform – NexJ Connected Wellness ( https://nexjhealth.com/ ), supported by a personal health coach and which complements the rehabilitation plan. This would include, for example, setting targets for activity that would be monitored with NexJ; educational materials; and support with medication adherence by reminders. The design of the application is outlined in Appendix 4. The NexJ platform will include the following sections: Case Plans with Educational Workbooks, Trusted Educational Content (Health Library), Symptom Tracking, Goal Setting and Reporting. Timing of Sessions All participants will receive health coaching sessions up to once a week. Participants who are using NexJ will have assigned content between sessions. Due to the heterogeneous nature of Long-COVID presentation, timing of clinical rehabilitation sessions will be individualized based on the treatment plan. This information will be recorded for each participant. Criteria for discontinuing or modifying allocated interventions {11b} Decisions about modifying individual rehabilitation care or health coaching will be made in collaboration with the most responsible healthcare provider and the Principal Investigator. No predefined criteria will be used with respect to modifying individual interventions. The trial will be stopped if more than 25% of participants in the intervention group experience at least a 20% increase in severity in their WHODAS sum score. There will be no stopping criteria for benefit given the short duration of the study. Strategies to improve adherence to interventions {11c} No particular strategy will be implemented to improve adherence to the intervention as this is an outcome of the study. As part of the process evaluation, we are examining factors affecting adherence to the intervention. We will evaluate any differences in adherence between the treatment and intervention groups. Relevant concomitant care permitted or prohibited during the trial {11d} As outlined in Table 1, only other trials providing treatment for Long COVID will be prohibited. All other concomitant care is permitted and will be documented. Provisions for post-trial care {30} In the event of a study-related injury or illness, participants will be provided with appropriate medical treatment and care. Financial compensation for lost wages, disability, or discomfort due to an injury or illness is not generally available. After study completion, participants will not have access to the NexJ Connected Wellness platform as this is not publicly available. The participants’ most responsible care provider will ensure a transition back to or continuation of standard care, as required. Outcomes {12} Primary Outcome To evaluate the primary outcome, improvement in quality of life, we will use the total sum score of the WHO Disability Assessment Scale (WHODAS 2.0) self-assessment. The WHODAS is the 36-item self-report questionnaire measuring health and disability from the previous 30 days across six domains of functioning: cognition, mobility, self-care, getting along, life activities and participation. Responses are scored on a 5 point Likert scale: None [0], Mild [1], Moderate [2], Severe [3], and Extreme/Cannot Do [4].(32) The WHODAS 2.0 has been validated using a cross-cultural approach in 19 countries and within 4 subgroups (general population, populations with physical problems, populations with mental or emotional problems, and populations with problems related to substance use). The WHODAS 2.0 showed excellent overall test-retest reliability (ICC=0.98) and internal consistency (Cronbach’s alpha= 0.98). The survey also showed good cross-cultural sensitivity and concurrent validity.(32) 3.5.2 Secondary Outcomes Long COVID Characteristics To describe the population and their experience with Long COVID, we will administer the WHO Post COVID Case Report Form (CRF) Modules 1,2 and 3 at baseline and only Module’s 2 and 3 at 12 weeks.(33) The CRF Module 1 captures demographics, pregnancy, pre-COVID health status, and details about the acute COVID infection. CRF Modules 2 and 3 collect vaccination status, occupational status, functioning, post-COVID symptoms, clinical tests and scales (including neurological, radiographic, blood tests, heart and lung function, mental health, function, and musculoskeletal tests), new diagnoses or complications related to COVID infection, and health service use, symptoms.(33) The CRF will be completed using health record review whenever possible, with missing information completed by interview with the participant. Currently, little is known about the long-term consequences of infection with COVID-19. In response to this, the WHO has created the WHO Post COVID Case Report Form, which will allow health care providers internationally to collect information on COVID-19 systematically. The use of this CRF will allow for the trial dataset to be aligned with the global WHO Clinical Platform and contribute to expanding our knowledge on Post-COVID-19 condition(s). All other secondary outcome measures are described in Table 3. Table 3. Secondary Outcomes Measure Description Properties Cognitive Testing Executive function, Visual attention, Task switching The Oral Trail Making Test (O-TMT) (versions A and B) will be used to evaluate executive function, visual attention and task switching in participants. During O-TMT A, participants will be asked to count out loud from 1 to 25 and is primarily a measure of processing speed and simple attention. During O-TMT B, participants will be asked to alternate saying numbers and letters (1-A, 2-B, etc.) and is a measure of mental flexibility. Time to completion as well as total errors are recorded (34,35). The use of time and error rate led to slightly improved classification rates for cognitive impairments compared to either alone.(36) Verbal learning and memory The Hopkins Verbal Learning Test-Revised (HVLT-R) will be used to evaluate verbal learning and memory capabilities in participants.(37) The HVLT consists of a 12-item word list, composed of four words from each of three semantic categories. The list is read to participants at a rate of approximately 2 words per second. Participants are then asked to free recall the list of words. This is repeated for 3 trials. After the third trial and a 20-25 minute delay (with no forewarning), participants will again be asked to free recall the 12 words and then will be read 24 words and asked to say “yes” after each word that appeared on the recall list (12 targets) and “no” after each word that did not (12 distractors).(38) The HVLT is available in 6 forms to reduce test-retest learning effects, takes no more than 10 minutes to administer and is shown to be well tolerated by participants.(37) Attention, Working memory The Digit Span subset, a component of the Working Memory Index of the Weschler’s Adult Intelligence Scale - 4 th Edition (WAIS-IV), will be used to assess attention and working memory.(39) Participants will be read a series of numbers and then asked to recall the numbers to the examiner in order (forward span), in reverse order (backward span) and in sequence (sequence span). Participants will complete spans of increasing length, with two trials at each length, until an error is made on both trials of a given length. Digit Span has shown good internal consistency and test-retest reliability across age groups.(39,40) Verbal fluency The Phonemic and Semantic Verbal Fluency (or Controlled Oral Word Association Test [COWAT]) test will be used to assess verbal fluency. Participants will be given one minute to produce as many unique words as possible: 1) within a semantic category (category fluency for Animals); and 2) starting with a given letter (letter fluency for letters F, A and S). The COWAT has been shown to have sensitivity to brain lesions and conditions with impaired cognition (e.g., traumatic brain injury). Population norms are available for the COWAT for a broad age (16-95) and education (0-21 years).(41,42) PHQ-9 Depression A 9-item questionnaire that assesses the severity of depression symptoms experienced within the last two weeks. Participants are asked to rate each symptom of depression on a Likert scale from 0 (not at all) to 3 (nearly every day), with total scores ranging from 0 (minimal depression) to 27 (severe depression). The PHQ-9 has strong methodological properties with an internal consistency of 0.89 and strong test re-test reliability.(43) GAD-7 Anxiety A 7-item questionnaire that assesses the severity of anxiety symptoms experienced within the last two weeks. The initial validation study, conducted by Spitzer et al. (2006), demonstrated high internal consistency (α=0.92) and test-retest reliability (intraclass correlation = 0.83).(44) PSQI Sleep The Pittsburgh Sleep Quality Index (PSQI) is a self-report questionnaire that assesses sleep quality in the previous month and takes 5-10 minutes to complete. It has been translated into over 50 languages. Using a threshold score of greater than 5, the PSQI showed a diagnostic sensitivity of 89.6% and specificity of 86.5% (kappa = 0.75, p < 0.001) in distinguishing “good” and “poor” sleepers.(45) PSTD Checklist 5 Post-Traumatic Stress Disorder A 20-item self-report measure that assesses the presence and severity of PTSD symptoms, corresponding with DSM-5 criteria for PTSD. PCL-5 scores exhibit strong internal consistency (α = .94), test-retest reliability (r = .82), and convergent (rs = .74 to .85) and discriminant (rs = .31 to .60) validity.(46) EQ-5D-5L Quality of Life This is a 5-item questionnaire that assesses health-related quality of life, including mobility, self-care, ability to participate in one’s usual activities, pain or discomfort, and anxiety or depression and a Visual Analogue Scale (VAS) which asks participants to evaluate their overall health on a scale from 0-100. It is available in multiple languages and there are standardised scores for patient populations in different settings. The EQ-5D-5L is able to define a unique health state based on the responses to each of the five dimensions of health described above.(47) AUDIT Alcohol Use The AUDIT questionnaire is designed to assess alcohol consumption, drinking behavior, adverse reactions, and alcohol-related problems. Among those who were known to misuse alcohol, the AUDIT successfully detected an alcohol use disorder 99% of the time (48). ASSIST Alcohol and Substance Use The ASSIST is a brief interview collecting information regarding use of tobacco, alcohol, cannabis, cocaine, amphetamine type stimulants, sedatives, hallucinogens, inhalants, opioids, and other drugs. Internal Consistency (Chronbach’s alpha) was over 0.80 for the majority of domains and good concurrent validity(49,50). FSS Fatigue The Fatigue Severity Scale is a 9-item self-report that measures the severity and functional impact of fatigue. The scale demonstrated good internal consistency (Cronbach’s α 0.88), as well good test-retest reliability and sensitivity to clinical change.(51) Fatigue Numeric Rating Scale Fatigue A single item patient reported outcome, scored on a scale of 0-10, with good test-retest reliability (ICC=0.79, p < 0.008) and sensitivity to change.(52) Pain Numeric Rating Scale Pain The Pain Numeric Rating Scale will be used to assess pain intensity using a 0–10 ranking scale, where 0 represents “no pain” and 10 “unbearable pain”. The scale shows good test-retest reliability (ICC=0.72 for single item), and sensitivity(53). Pain may be categorized using Mild (scores ≤5), Moderate (scores 6-7) or Severe (scores ≥8).(54) MRC Dyspnoea Scale Breathlessness A 5-item self report scale that evaluates statements of perceived breathlessness. The scale has good correlation to level of disability due to breathlessness.(55) WEMWBS Wellbeing The Warwick Edinburgh Mental Wellbeing Scale (WEMWBS) (short version) is a 7-item scale which measures multiple aspects of mental wellbeing(56). It has been validated in general population samples and in English and French(57), and is sensitive to change.(58) Predictors and Potential Confounders At the first assessment we will collect information on potential predictors and potential confounders as listed in Table 4. Table 4. Predictors, potential confounders and effect modifiers Predictors and potential confounders Demographic details At baseline, we will collect information on ethnicity, gender identity, education, income, employment, housing and living circumstances Past medical history This will include body mass index and past medical and mental health disorders Impact of COVID-19 infection For those who tested positive we will record details of the severity and impact of the COVID-19 infection including neurological symptoms such as anosmia and headaches, length of time self-isolating and time off work IEQ-SF The Injustice Experience Questionnaire (IEQ) is a 12-item self-report that assesses perceived injustice associated with injury. The IEQ showed good correlation with measures of catastrophic thinking (r=.75, p <.01), fear of movement/re-injury (r=.58, p<.01), depression (r=.66, p<.01), and pain severity (r=.54, P<.01).The IEQ also demonstrated good test-retest reliability.(59) Adverse childhood events questionnaire (ACE) The ACE-Q is a 17 item self-report questionnaire assessing types of adverse exposures during childhood including psychological, physical and sexual abuse as well as household dysfunction. The ACE questionnaire study found strong relationships between childhood exposure and disease conditions, health risk factors and a strong dose-response relationship between number of exposures and risk factors for death.(60) Process Evaluation To inform the implementation of the intervention beyond the clinical trial and describe the intervention process we will use the RE-AIM framework.(31) We will assess Reach by recording what proportion of eligible patients participate in the trial and comparing characteristics of participants to non-participants. Effectiveness will be assessed in the clinical trial and separately stratified by sex. We will also record dropouts by sex and severity. We will conduct qualitative interviews with participants to better understand the reasons for participating, the experience of using the NexJ app and any reasons for drop out. We will use a thematic analysis and aim to complete at least 20 user interviews and will continue until we achieve data saturation. We will gather usage data from NexJ. Adoption at the setting level will be assessed by comparing uptake in the different clinics supplemented by qualitative interviews of clinical staff. Adoption at the staff level will compare high referrers to the study to low referrers and doing qualitative interviews with staff in each group. Implementation will be assessed with a study specific-adherence scale. Maintenance at an individual and setting level will be assessed using the Consolidated Framework for Implementation Research (CFIR) to inform qualitative interviews with key stakeholders to identify barriers and facilitators to introducing NexJ in outpatient clinics. Economic Evaluation We will conduct a cost-utility analysis of an electronic case management system compared with usual care from a perspective of the publicly funded health care system. Costs and outcomes will be assessed within the follow up period of the trial. Resources and associated costs required to set up and operate a unique instance of the NexJ platform will be estimated from the budget review and staff interview. We will collect health care utilization data, such as hospitalization, emergency department visits, physician visits, prescriptions, and the efficacy of the intervention, from the concurrent trials. We will derive health utility value from the EQ-5D-5L using the Canadian validated algorithm.(61) Quality-adjusted life years (QALYs) will be estimated using the total area under the curve method.(62) Unit costs for each health care resource will be obtained from Canadian Sources. Costs will be expressed in 2021 Canadian Dollars. Participant timeline {13} Administration will occur as per Time and Events Schedule in Table 5. Clinical visits will occur as needed and will be determined during the initial assessment. Clinical visits are not outlined in the time and event schedule as these are a part of routine care. Self-report measures will be completed at home prior to each study visit using the study electronic data capture system (EDCS). Participants will be able to leave and return to the questionnaires whenever they need to complete them. It is anticipated the first and last visit will take approximately 45 minutes, while week 4 and 8 will take approximately 30 minutes. Participants will complete the WHODAS first and all responses are mandatory. All other self-report measures will be completed in a structured order. Table 5. Time and Events Schedule Measures Time to Complete (Minutes) Administration Baseline Week 4 Week 8 Week 12 WHO Post COVID CRF Module 1 Variable Chart Review X WHO Post COVID CRF Module 2 Variable Chart Review X X WHO Post COVID CRF Module 3 Variable Chart Review X X Demographics <5 Self-Report X ACE-Q 5 Self-Report X Injustice Experience Questionnaire (IEQ-SF) <5 Self-Report X WHODAS (36) 5 Self-Report X X X X PHQ-9 <5 Self-Report X X X X GAD-7 <5 Self-Report X X X X PCL-5 5 Self-Report X X X X EQ-5D-5L <5 Self-Report X X X X AUDIT <5 Self-Report X X ASSIST 5-10 Interview X X Fatigue Severity Scale <5 Self-Report X X X X PSQI 5 Self-Report X X X X Warwick Edinburgh Mental Wellbeing Scale (WEMWBS) 5 Self-Report X X Pain Numeric Rating Scale <5 Self-Report X X X X MRC Dyspnoea Scale <5 Self-Report X X X X Cognition (Trailmaking, Hopkins Verbal Learning, Digit Span, Phonemic/Semantic Verbal Fluency) 30 Interview X X Qualitative Interview (Optional) 30 Interview X Sample size {14} We have based the sample size calculation on the sum of domain scores of the WHODAS 36, as the recommended assessment for Long COVID patients.(33) At the time of writing this protocol, there were no published scores of the WHODAS 36 in people with Long COVID. Therefore, we have based our sample size calculation on WHODAS 36 scores from 25 randomly selected patients attending an existing clinic for Long COVID at TOH run by OWN. These patients had a mean sum of domain scores of 17 (SD=4). The minimally important clinical difference on the WHODAS is about a 10% change in scores.(32) Using these assumptions, we need to recruit at least 126 participants (63 in each group) to have 80% power to detect a 10% change in scores assuming an alpha of 0.05. Allowing for 20% drop out would mean a recruitment target of 152 (76 in each group) people. Recruitment {15} Participants will be recruited at TOH through two potential recruitment streams. The first clinic sees Ontario workers who were infected by SARS-CoV-2 at their worksite, who have made a claim to the Ontario WSIB and are assessed by the OWN based at TOH. The second stream is any clinics within TOH which are seeing patients with Long COVID. These are either clinics specifically for people with Long COVID, for example within respirology, infectious diseases or psychiatry. The anticipated flow of recruitment is outlined in Figure 1 below. Assignment of interventions: Allocation Sequence generation {16a} Randomization will be done remotely by the Ottawa Methods Centre (OMC) through an electronic randomization system. Participants will be randomized at enrollment by a delegated study staff member. As participants are created in the electronic data capture system (EDCS), they are automatically randomized. The delegated study staff member will be informed of the allocation at the time of randomization. Allocation will be a 1:1 ratio into the treatment arms. Participants will be stratified by sex and duration of symptoms. The reasons for stratification by sex are that the mortality rate in males is higher than in females and that outcomes may be affected by gendered occupations.(63–66) We will stratify by the duration of symptoms into two groups: (1) those who at enrolment have had symptoms since the onset of their index illness for 12 to 23 weeks, and (2) those who have had symptoms at enrolment for 24 weeks or longer, which is consistent with the classification of Long COVID in the NICE guidelines. We are stratifying for duration of illness as this is one of the main determinants of outcomes. Concealment mechanism {16b} Not applicable. Since the interventions are assigned through random computer generation, allocations are not visible in advance, and no concealment is required. Implementation {16c} Once participants have consented and completed screening determining eligibility, they will be registered in the study electronic data capture and randomization system by the delegated research staff member. Once the participant is registered, the system will automatically allocate the participant to the intervention. Assignment of interventions: Blinding Who will be blinded {17a} Due to the nature of the intervention, a behavioural intervention where both patient and clinician must use an electronic platform, it is not possible to blind either group to their allocation. Data analysts and manuscript writers will be blind to the identity of the two groups which will be referred to as group A and group B. Once initial manuscript preparation is complete, the groups will be unblinded. We will also assess potential bias in recruitment during an interim analysis. Procedure for unblinding if needed {17b} Not applicable – all participants and treating clinicians are unblinded to the intervention. Data collection and management Plans for assessment and collection of outcomes {18a} All self-reported outcome measures will be administered via the EDCS for all study visits. Interview measures, when done remotely, will be completed using a videoconferencing platform. Information from the WHO Post-COVID Assessment CRF will be entered by delegated study staff into the EDCS. Cognitive assessments will be administered by a trained research staff member. The delegated study staff member will receive direct training from an experienced Psychologist, including rehearsal and independent evaluation, prior to administration with participants. Plans to promote participant retention and complete follow-up {18b} A major difficulty in all clinical research is ensuring participants attend their visits and stay enrolled in the study. Efforts will be made to minimize the time between being approached about the study and the baseline visit. We anticipate lost to follow-up to be no more than 20%. While there is currently no available literature on the lost to follow up rates for Long COVID rehabilitation, the case management platform we are using has demonstrated significantly higher levels of retention in difficult to treat populations.(24) For those participants in the intervention arm, daily and weekly reminders will be programmed into the NexJ Connected Wellness platform to encourage regular use and increase connectedness with the platform, increasing retention. We will implement an escalated approach if contact is lost with individuals between study visits. The appropriate response will be determined in collaboration with the Principal Investigator, particularly if there is a potential safety concern. If contact is made with the participant and they are no longer interested in participating, the delegated study staff member will make every effort to ascertain why they are withdrawing their consent. Participants will be sent the link to complete their self-report questionnaires at each time point unless they have withdrawn their consent for participation. Data management {19} All study outcome data will be directly entered into an EDCS. Data will be automatically coded and the code will be described using a data dictionary. Range checks will be included for illogical entries. Missing items will be flagged for self-entry, however, participants can bypass the warning. A delegated study staff member will follow-up on the missing entry to confirm if the question was missed or the participant is refusing to answer. The EDCS is a username and password protected web-based system. All network, server security and privacy settings are regularly tested and comply with Health Canada recommendations and Good Clinical Practice (GCP) for secured data management services.(67,68) The EDCS is hosted on a physical server, not in the cloud, that is located at TOH data centre in a secure server room with limited access to authorized personnel behind lock doors. The web/database server is behind the TOH firewalls. The OHRI web site is secured with the highest rating from Entrust SSL virtual test. The data transfer between the client and server is protected with Entrust SSL 256-bit encryption. All data transfers between the client computers/browsers and the server/database are encrypted via https. Confidentiality {27} All records will automatically be assigned a unique Participant ID during randomization. The Participant ID will be recorded on a master linking log. The master linking log will be password protected and stored with limited access as per institutional policy. The Participant ID will appear on all documentation included in a participant’s research chart, including study forms and correspondence, in order to maintain participant confidentiality. All correspondence with participants will be de-identified, removing names and other potentially identifying information, prior to being included in the study chart. Some documentation will remain identifiable including the Informed Consent Form, the Participant Information Form and the Emergency Contact Form. These will not be stored with documentation identified with a Participant ID. Hard copy documentation will be stored in a double locked area (e.g. locked cabinet and secure office space). Study documents will be password protected and a log kept separately from the documents so that access to the files is not lost in the event of staff turnover or during the archiving period. Electronic documents will not be stored on mobile devices (such as a USB or directly on a laptop). Documents requiring de-identification must use an approved method. Electronic documents must be redacted so that the information removed cannot be recovered at a later time utilizing a tool such as Adobe Pro “Redact” feature, permanently obscuring the data. Hardcopy documentation will be redacted using only a “china marker”, which completely obscures the data. Sharpie, pen and other writing tools are not permitted as they do not permanently obscure/destroy the data. Participants’ study information will not be released unless a delegated study staff member obtains written permission from the participant or where required by law. Participants will not be identified in study presentations or publications. Once all study activities are complete all study records and data exports will be archived at a secure storage facility for a period of ten years, as per the applicable N2 SOP and GCP regulations. The ten-year period will begin from the date the last informed consent form is signed. Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33} Not applicable. There are currently no ancillary trials planned. Statistical methods Statistical methods for primary and secondary outcomes {20a} The OMC will complete all data analyses. Baseline characteristics will be presented as means (or medians) with associated measures of variation for continuous variables, or frequencies and proportions for categorical data. We will use an intention-to-treat analysis based on all randomized participants. Additionally, we will analyze the primary and secondary outcomes based on the treatment received. Analyses will utilize a GBA+ focused Health Equity Impact Assessment (HEIA)(69) approach to examine how sex and gender interact with socioeconomic status, age, race/ethnicity and rural/urban residence. Analysis of primary and secondary outcomes will use relative risks and mean differences and be calculated and presented with 95% CIs. We will include subgroup analyses of participants by age, sex, and severity of Long COVID. The effects of group (control vs. experimental), Long COVID severity, and adverse childhood events on the linear change over time in the primary outcome (measured at 4 time points) will be analyzed using hierarchical regression. Bivariate associations between primary and secondary outcomes (and among secondary outcomes) measured at baseline and at the end of the study will be estimated with Pearson correlation coefficients (or Spearman correlation coefficients for non-parametric data). Economic Evaluation Results of a cost-utility analysis will be presented as incremental cost per QALY gained. The incremental cost and incremental outcome will be estimated using generalized linear models that explicitly allow for the modelling of normal and non-normal distributional forms of data. The incremental cost-effectiveness ratio will be obtained through the difference in the mean costs of the two strategies divided by the difference in the mean QALYs for each strategy as denoted by the coefficient of the intervention indicator variables. Uncertainty in the analysis will be addressed by estimating 95% confidence intervals using a non-parametric bootstrapping method. For this study, we will obtain 10,000 estimates of costs and outcomes for each strategy. Results from the bootstrapping exercise will also be used to show cost-effectiveness acceptability curves, which represent the probability of NexJ being cost-effective over a range of willingness to pay values that the health system may be willing to pay for an additional unit of QALY. Interim analyses {21b} We will do a health equity impact assessment at six months to ensure the study has addressed potential health inequities in recruitment, treatment, and assessment using the Ontario Health Equity Impact Assessment (HEIA) tool.(69) Methods for additional analyses (e.g. subgroup analyses) {20b} Not applicable. There are currently no planned subgroup analyses. Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c} Efforts will be made to minimize missing data, although it is possible that some amount of missing data may occur. We will examine the pattern of missing data by comparing characteristics of participants with missing data to those of participants with complete data to examine the assumption of Missing at Random. In the case of substantial missingness (e.g., >5%), missing covariates and outcomes will be imputed using multiple imputation with m=10 imputed data sets prior to analysis. Plans to give access to the full protocol, participant level-data and statistical code {31c} The Principal Investigator will retain ownership of the dataset through the 10-year archiving period. The protocol will be made available open-access and will be published, at a minimum, on an open-science platform such as Open Science Framework or medRXiv. The anonymized data set will be shared on an open science platform, such as Open Science Framework or Zenodo. The anonymized dataset may also be shared with the WHO to facilitate global post-COVID-19 research and treatment efforts. Oversight and monitoring Composition of the coordinating centre and trial steering committee {5d} Committee Responsibilities Membership Trial Steering Committee Approval of the final protocol; Reviewing and advise on progress of study; facilitation of study conduct; end point evaluation; manuscript coordination, knowledge translation Investigators as listed, other members as outlined in the Trial Steering Committee charter. Trial Management Committee (Coordinating Centre responsibilities) Protocol management, study documentation, ethics, contracts, study planning, day-to-day activities, budgets, monitoring, data verification, randomization, support study registered health professionals, investigator support for trial activities, liaise with platform service provider; organize steering committee meetings, implement steering committee action items Principal Investigator, co-Principal Investigator, Clinical Research Program Manager, Clinical Research Coordinator, Clinical Research Assistant Composition of the data monitoring committee, its role and reporting structure {21a} An independent Data and Safety Monitoring Committee (DSMC) has been convened to assess the progress of the clinical trial, the integrity of the data, the safety of all participants and to provide recommendations to the Principal Investigator(s). The members of the DSMC serve in an individual capacity and provide their expertise and recommendations. The DSMC will review cumulative study data to evaluate safety, study conduct, scientific validity, and data integrity of the study. A charter will outline the full responsibilities of the DSMC. At a minimum, the general responsibilities of the DSMC will be: To evaluate any reports of safety-related events in the study to ensure the ongoing safety of participants; To consider factors external to the study when relevant information becomes available, such as scientific or therapeutic developments that may have an impact on the safety of the participants or the ethics of the study; To review the conduct of the study; To make recommendations to continue, modify, or terminate the study. Membership will be comprised of four independent, interdisciplinary members. Possible fields of expertise include statistics/biostatistics, epidemiology, methodology, psychiatry and the ethics of clinical trials. Members will be identified in the DSMC charter. Adverse event reporting and harms {22} Participant well-being and safety will be monitored by the Investigators and Registered Health Professionals (RHPs), within the restrictions of their respective professional colleges. Adverse Events will be collected at each study visit. Standard operating procedures (SOPs) will be developed for escalation of participant safety concerns, for example by setting a threshold increase on mental health scales where the Principal Investigator, or appropriate most responsible care provider, is notified for follow-up. If a significant worsening of symptoms occurs, the individual notified or Principal Investigator will follow-up with the participant and will provide intervention as necessary. Reporting of Adverse Events and Serious Adverse Events will follow institutional procedures as laid out in SOPs and Research Ethics Board (REB) guidance. Participants may find some questions in the questionnaires uncomfortable. Participants may refuse to answer any questions to which they do not want to respond. Expected adverse events include worsening fatigue, decline in symptoms reported at baseline related to the study intervention, and eye strain/fatigue from using the smartphone application. Frequency and plans for auditing trial conduct {23} An internal study monitor will be selected prior to the start of the trial. The monitor will not be involved in data collection activities and will be one step removed from the clinical trial. Before the launch of recruitment, the internal monitor will ensure that appropriate training has been completed and documented for all delegated study staff. After enrollment of the first participant, the internal study monitor will review all documentation for this participant to ensure any errors or challenges are identified and resolved before being carried through subsequent participants. Throughout the duration of the study, the internal monitor will perform monitoring visits on a minimum quarterly basis, or more frequently as needed based on recruitment rates. An internal monitoring plan will guide the process and materials to be reviewed at each visit, as well as follow-up procedures. At the end of study, the monitor will lead the study close out activities in collaboration with the study staff to ensure that all study records and essential documentation are complete and ready for analysis, REB closure and archiving. Throughout the study, the Ottawa Hospital Research Institute (OHRI) Clinical Facilitators may also audit the study. These audits may be planned or unplanned. If an audit is requested, the study team will assist the OHRI in completing their review of the study. If the internal monitor discovers significant or repeated issues in their monitoring visits, they may request the assistance of the OHRI Clinical Facilitators for their recommendations. Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25} Any subsequent modifications to the study protocol, including changes to study objectives, study design, patient population, sample sizes, study procedures, or significant administrative changes will be agreed upon by the Investigators and submitted to the REB of record for review and approval prior to implementation. Participants will be informed in writing of any modifications or new information that may impact their willingness to participate in the study. If required, participants may also be asked to sign a Consent Update Form, as approved by the REB. Dissemination plans {31a} We plan to take a diverse approach to our knowledge mobilization and dissemination plan. We have engaged the Public Health Agency of Canada (PHAC) as Knowledge Users in our study. PHAC will work with the investigator team to identify relevant targets of knowledge exchange activities within the federal health portfolio, as well as with national and international stakeholders. Primary outcomes publications refer to any presentation or publication that presents data on the primary outcome measure as detailed in this protocol. The primary outcome publication will be submitted within 6 months of the completion of data collection. The primary outcomes publication will be open-access and any secondary publications will be made open-access whenever possible. All study results will be released to study participants, the general medical community, the general public and other identified stakeholders. Other forms of dissemination include academic publications, conference presentations, stakeholder meetings and presentations to the general public. Lay knowledge products will be designed in collaboration with lived experience partners to ensure that dissemination is impactful and relevant to the community. Discussion There is currently little evidence about the optimal treatment of Long COVID patients or the use of digital health platforms in this population. There are currently no systematic reviews of treatment for Long COVID and much of the existing literature is considered low quality evidence. Important operational issues relate to the privacy and confidentiality of any information stored on the app, however the study team has ensured safeguards are in place to minimize this risk. Additionally, navigating virtual visits and fluctuating lockdowns poses variable challenges throughout the duration of the study. The protocol has been designed to be delivered hybrid or fully virtual, if required, to seamlessly accommodate any changes in access to in-person resources. The results of this trial could result in rapid, scalable, and personalized care for people with Long COVID which will decrease morbidity after an acute infection. Results from this study will also inform decision making in Long COVID and treatment guidelines at provincial and national levels. Trial status This study received initial approval by the OHSN-REB in September 2021, with an amended protocol approved (protocol version date 23 Feb 2022). Recruitment was opened in May 2022. At the time of writing this manuscript, one participant had been enrolled. The estimated completion date for primary data collection is May 2023. Abbreviations ACE-Q; Adverse Childhood Events Questionnaires; ASSIST; Alcohol, Smoking and Substance Interview Screening Test; AUDIT; Alcohol Use Disorders Identification Test; CIHR; Canadian Institutes of Health Research; COWAT; Controlled Oral Word Association Test; CRF; Case Report Form; DSMC; Data and Safety Monitoring Committee; ECM; Electronic Case Management; EDCS; Electronic Data Capture System; FNRS; Fatigue Numeric Rating Scale; FSS; Fatigue Severity Scale; GAD-7; Generalized Anxiety Disorder 7-item scale; HEIA; Health Equity Impact Assessment; HVLT-R; Hopkins Verbal Learning Test Revised; GCP; Good Clinical Practice; IEQ-SF; Injustice Experience Questionnaire – Short Form; NICE; National Institute for Healthcare and Excellence; OHRI; Ottawa Hospital Research Institute; OHSN-REB; Ottawa Health Sciences Network Research Ethics Board; OMC; Ottawa Methods Centre; OWN; Ontario Workers Network; PCL-5; PTSD Checklist-5; PCR; polymerase chain reaction; PHAC; Public Health Agency of Canada; PHQ-9; Patient Health Questionnaire 9-item scale; PNRS; Pain Numeric Rating Scale; PSQI; Pittsburgh Sleep Quality Index; QALY; Quality Adjusted Life Years; RAT; Rapid Antigen Test; REB; Research Ethics Board; RHP; Registered Health Professional; O-TMT; Oral Trail Making Test; TOH; The Ottawa Hospital; WAIS-IV; Weschler’s Adult Intelligence Scale - 4 th Edition; WEMWBS; Warwick Edinburgh Mental Wellbeing Scale; WHO; World Health Organization; WHODAS; WHO Disability Assessment Scale; WSIB; Workplace Safety and Insurance Board. Declarations Acknowledgements Not applicable. Authors’ contributions {31b} SH is the Principal Investigator; he conceived the study, led the proposal and protocol development. JW is the co-Principal Investigator; he conceived the study, contributed to development of the proposal and protocol. NE is the Clinical Research Program Manager; she drafted the proposal and the protocol. KT is a co-Investigator and Health Economist; she designed the cost effectiveness analysis plan. DC is a co-Investigator and biostatistician; he developed the statistical analysis plan. All authors contributed to the proposal, refinement of the study protocol, and all authors read and approved the final manuscript. Funding {4} This study is funded by the Canadian Institutes of Health Research (CIHR). The funders have no role in the design or conduct of the study or the decision to publish results. Availability of data and materials {29} The Principal Investigator will retain ownership of the dataset through the 10 year archiving period. Once the primary outcomes manuscript is published, the anonymized data set will be shared on an open access platform, such as Open Science Framework or Zenodo. Prior to this, any data required to support the protocol can be supplied upon request to the Principal Investigator (SH). Ethics approval and consent to participate {24} Ethics approval for this study has been granted by the Ottawa Health Sciences Network Research Ethics Board (OHSN-REB) (Protocol ID: 20210533-01H). Written, informed consent to participate will be obtained from all participants. Consent for publication {32} Model consent form available from corresponding author on request. Competing interests {28} MK has consulting or speaking fees, unrelated to this trial or intervention, from HLS, Janssen, Otsuka, Lundbeck in last 2 years. 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Wittkampf KA, Naeije L, Schene AH, Huyser J, van Weert HC. Diagnostic accuracy of the mood module of the Patient Health Questionnaire: A systematic review. Gen Hosp Psychiatry. 2007;29(5):388–95. Robert L Spitzer, Kurt Kroenke, Janet B W Williams, Bernd Lowe. A brief measure for assessing generalized anxiety disorder. Arch Intern Med. 2006;166(10):1092–7. Buysse Charles F Reynolds Ill DJ, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research [Internet]. Vol. 28, Psychiatry Research. Available from: https://journals-scholarsportal-info.proxy.bib.uottawa.ca/pdf/01651781/v28i0002/193_tpsqiaifppar.xml Blevins CA, Weathers FW, Davis MT, Witte TK, Domino JL. The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): Development and initial psychometric evaluation. J Trauma Stress. 2015 Dec;28(6):489–98. Rabin R, de Charro F. EQ-5D: A measure of health status from. Ann Med. 2001;33:337–43. Carey KB, Carey MP, Chandra PS. Psychometric evaluation of the Alcohol Use Disorders Identification Test and Short Drug Abuse Screening Test with psychiatric patients in India. J Clin Psychiatry. 2003 Jul;64(7):767–74. Humeniuk R, Ali R, WHO ASSIST Phase II Study Group. Validation of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and Pilot Brief Intervention. Geneva; 2006. Humeniuk R, Ali R, Babor TF, Farrell M, Formigoni ML, Jittiwutikarn J, et al. Validation of the alcohol, smoking and substance involvement screening test (ASSIST). Addiction. 2008 Jun;103(6):1039–47. Krupp LB, Larocca NG, Muir Nash J, Steinberg AD. The fatigue severity scale: Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989;46(10):1121–3. Minnock P, Kirwan J, Bresnihan B. Fatigue is a reliable, sensitive and unique outcome measure in rheumatoid arthritis. Rheumatology. 2009;48(12):1533–6. Jensen MP, Turner JA, Romano JM, Fisher LD. Comparative reliability and validity of chronic pain intensity measures. Pain. 1999;83(2):157–62. Boonstra AM, Stewart RE, Köke AJA, Oosterwijk RFA, Swaan JL, Schreurs KMG, et al. Cut-off points for mild, moderate, and severe pain on the Numeric Rating Scale for Pain in patients with chronic musculoskeletal pain: Variability and influence of sex and catastrophizing. Front Psychol [Internet]. 2016;7:1466. Available from: https://www.frontiersin.org/articles/10.3389/fpsyg.2016.01466/full Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax. 1999;54(7):581–6. Tennant R, Hiller L, Fishwick R, Platt S, Joseph S, Weich S, et al. The Warwick-Dinburgh mental well-being scale (WEMWBS): Development and UK validation. Health Qual Life Outcomes. 2007; Trousselard M, Steiler D, Dutheil F, Claverie D, Canini F, Fenouillet F, et al. Validation of the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) in French psychiatric and general populations. Psychiatry Res. 2016;245:282–90. Maheswaran H, Weich S, Powell J, Stewart-Brown S. Evaluating the responsiveness of the Warwick Edinburgh Mental Well-Being Scale (WEMWBS): Group and individual level analysis. Health Qual Life Outcomes. 2012;10(156). Sullivan MJL, Adams H, Horan S, Maher D, Boland D, Gross R. The role of perceived injustice in the experience of chronic pain and disability: Scale development and validation. J Occup Rehabil. 2008;18(3):249–61. Felitti VJ, Anda RF, Nordenberg D, Williamson DF, Spitz AM, Edwards V, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: The adverse childhood experiences (ACE) study. Am J Prev Med. 1998; Xie F, Pullenayegum E, Gaebel K, Bansback N, Bryan S, Ohinmaa A, et al. A time trade-off-derived value set of the EQ-5D-5L for Canada. Med Care. 2016;54(1):98–105. Manca A, Hawkins N, Sculpher MJ. Estimating mean QALYs in trial-based cost-effectiveness analysis: The importance of controlling for baseline utility. Health Econ. 2005;14(5):487–96. Bai F, Tomasoni D, Falcinella C, Barbanotti D, Castoldi R, Mulè G, Augello M, Mondatore D, Allegrini M, Cona A, Tesoro D, Tagliaferri G, Viganò O, Suardi E, Tincati C, BerBai F, Tomasoni D, Falcinella C, Barbanotti D, Castoldi R, Mulè G, Augello M, Mondat MA, ingheli T, Varisco B, Battistini CL, Piscopo K, Vegni E, Tavelli A, Terzoni S, Marchetti G MA. Female gender is associated with long COVID syndrome: a prospective cohort study. Clin Microbiol Infect. 2021;S1198-743X. Izcovich A, Ragusa MA, Tortosa F, Marzio MAL, Agnoletti C, Bengolea A, et al. Prognostic factors for severity and mortality in patients infected with COVID-19: A systematic review. PLoS One. 2020;15(11):e0241955. Rovere-Querini P, De Lorenzo R, Conte C, Brioni E, Lanzani C, Yacoub MR, et al. Post-COVID-19 follow-up clinic: Depicting chronicity of a new disease. Acta Biomed. 2020;91(9-S):22–8. Sudre CH, Murray B, Varsavsky T, Graham MS, Penfold RS, Bowyer RC, et al. Attributes and predictors of long COVID. Nat Med. 2021;27:626–31. Government of Canada. Safeguarding your Research [Internet]. 2021. Available from: https://www.ic.gc.ca/eic/site/063.nsf/eng/h_97955.html International Council for Harmonisation of Tecnical Requirements for Pharmaceuticals for Human Use. Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) [Internet]. 2016. Available from: https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf Ministry of Health. Health Equity Impact Assessment Tool (HEIA) [Internet]. Governemnt of Ontario. 2008 [cited 2021 Jul 12]. Available from: https://www.health.gov.on.ca/en/pro/programs/heia/tool.aspx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 19 Jul, 2022 Reviewers invited by journal 19 Jul, 2022 Editor assigned by journal 16 Jun, 2022 First submitted to journal 03 Jun, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1723719","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":122305931,"identity":"941879b9-9aa4-4101-89b3-29b25e8de9aa","order_by":0,"name":"Simon 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1","display":"","copyAsset":false,"role":"figure","size":192284,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePatient flow\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1723719/v1/9a1cd171c162accdcb067fc9.jpg"},{"id":24367885,"identity":"05f51056-a4b6-482f-af32-64d2d001b32b","added_by":"auto","created_at":"2022-07-26 19:15:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1057466,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1723719/v1/1e46f5d2-214d-416c-b1b0-f032088e1426.pdf"}],"financialInterests":"","formattedTitle":"Enhancing COVID Rehabilitation with Technology (ECORT): Protocol for an open-label, single site randomized controlled trial evaluating the effectiveness of electronic case management for individuals with persistent COVID-19 symptoms.","fulltext":[{"header":"Administrative information","content":"\u003cp\u003eNote: The numbers in curly brackets in this protocol refer to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist item numbers. The order of the items has been modified to group similar items (see http://www.equator-network.org/reporting-guidelines/spirit-2013-statement-defining-standardprotocol-items-for-clinical-trials/). \u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.11580594679186%\"\u003e\n \u003cp\u003eTitle {1}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"65.88419405320813%\"\u003e\n \u003cp\u003eEnhancing COVID Rehabilitation with Technology (ECORT): An open-label, single site randomized controlled trial evaluating the effectiveness of electronic case management for individuals with persistent COVID-19 symptoms.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.11580594679186%\"\u003e\n \u003cp\u003eTrial registration {2a and 2b}.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"65.88419405320813%\"\u003e\n \u003cp\u003eClinicalTrials.gov\u003cbr\u003e NCT05019963\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.11580594679186%\"\u003e\n \u003cp\u003eProtocol version {3}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"65.88419405320813%\"\u003e\n \u003cp\u003eVersion 23 Feb 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.11580594679186%\"\u003e\n \u003cp\u003eFunding {4}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"65.88419405320813%\"\u003e\n \u003cp\u003eThis study is funded by the Canadian Institutes of Health Research (CIHR). The funders have no role in the design or conduct of the study or the decision to publish results.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.11580594679186%\"\u003e\n \u003cp\u003eAuthor details {5a}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"65.88419405320813%\"\u003e\n \u003cp\u003e(1) Clinical Epidemiology Program, Ottawa Hospital Research Institute (2) Department of Psychiatry, University of Ottawa (3) Department of Mental Health, The Ottawa Hospital, (4) Department of Surgery, The Ottawa Hospital (5) Ontario Workers Network, The Ottawa Hospital (6) No affiliation (7) Division of Infectious Disease, University of Ottawa (8) School of Epidemiology and Public Health, University of Ottawa (9) Department of Medicine, University of Ottawa (10) Centre of Infection, Immunity, and Inflammation, University of Ottawa (11) Department of Pharmacy, The Ottawa Hospital (12) School of Pharmaceutical Sciences, University of Ottawa (13) Division of Physical Medicine and Rehabilitation, University of Ottawa (14) Bruyere Research Institute (15) Parkinson\u0026rsquo;s Disease and Movement Disorders Center, Division of Neurology, Department of Medicine, The Ottawa Hospital (16) Neuroscience Program, Ottawa Hospital Research Institute (17) University of Ottawa Brain and Mind Institute (18) Department of Psychology, The Ottawa Hospital (19) School of Psychology, University of Ottawa (20) Public Health Agency of Canada (21) Department of Medicine, The Ottawa Hospital (22) Department of Biochemistry, Microbiology and Immunology, University of Ottawa \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.11580594679186%\"\u003e\n \u003cp\u003eName and contact information for the trial sponsor {5b}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"65.88419405320813%\"\u003e\n \u003cp\u003eTrial Sponsor: Ottawa Hospital Research Institute (OHRI)\u003c/p\u003e\n \u003cp\u003eContact name: Dr. Duncan Stewart\u003c/p\u003e\n \u003cp\u003eAddress: 501 Smyth Road, Ottawa, ON K1H 8L6\u003c/p\u003e\n \u003cp\u003eTelephone: (613) 798-5555, ext.79017\u003c/p\u003e\n \u003cp\u003eEmail: [email protected] \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.11580594679186%\"\u003e\n \u003cp\u003eRole of sponsor {5c}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"65.88419405320813%\"\u003e\n \u003cp\u003eThe sponsor (OHRI) had no role in the design of this study and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Introduction","content":"\u003cp\u003e\u003cstrong\u003eBackground and rationale {6a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn March 2020, the World Health Organization (WHO) declared the novel coronavirus (COVID-19) a global pandemic. At the time of writing this protocol in February 2022, Ontario had confirmed more than 628,000 cases of SARS-CoV-2 since testing began. Most recently, estimates in May 2022 show this number has climbed to 1.3 million cases.(1) For most of these patients, symptoms resolve within 4 weeks of onset. However, it is becoming apparent that a significant subset of infected patients are experiencing symptoms that persist long after the typical course of acute viral infection. These individuals experience a wide constellation of symptoms, with variable intensity over time and often varying from initial acute presentation.(2\u0026ndash;6) Currently, the prevalence and duration is unclear, nor is there evidence on the best course of rehabilitation for individuals to return to their desired level of function. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003e\u003cstrong\u003e1.1 What is post-COVID syndrome ?\u003c/strong\u003e\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe National Institute for Healthcare and Excellence (NICE) defines two distinct groups: ongoing symptomatic COVID (symptoms for 4-12 weeks) and post-COVID syndrome, which describes those with ongoing symptoms, not better explained by another diagnosis, for 12 weeks and longer.(7) The most common symptom experienced is persistent fatigue, followed by dyspnea, cognitive issues such as \u0026ldquo;brain fog\u0026rdquo; and cardiothoracic issues. (2,5,6,8) Other symptoms include headaches, muscle and joint pain, persistent cough and psychiatric conditions. (2,6,8,9) An early study found that nearly half of the sample had also experienced a decrease in their quality of life.(6) It is unclear who is most at risk for developing post-COVID syndrome. While severe illness or long time to acute recovery is predictably associated with poor long term outcomes, more than 35% of individuals with mild illness failed to return to baseline health status.(10) Women(2,4) and ethnic minorities (11) may also be at higher risk. Previous research from the SARS pandemic also suggests that social disadvantage, such as job loss or social stigma, were also risk factors for long-term symptoms.(12) The heterogeneous nature of symptoms and risk factors suggest that an \u0026ldquo;organ-based\u0026rdquo; or classification approach will not provide optimal outcomes for these patients. An integrated model for rehabilitation, including interdisciplinary care, enhanced case management and screening tools, should be examined.(13,14)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003e1.1.1 Nomenclature\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThere are at least four terms employed to describe \u0026nbsp;persistent COVID symptoms, including \u0026ldquo;Long COVID\u0026rdquo;, \u0026ldquo;COVID-19 syndrome\u0026rdquo;, \u0026ldquo;post COVID-19 syndrome\u0026rdquo; or \u0026ldquo;post-acute sequelae of SARS- CoV-2 infection\u0026rdquo;.(2) We have chosen to refer to the condition as Long COVID as this seems to be the term most preferred by patients.(15)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003e\u003cstrong\u003e1.2 Case Management in COVID-19 Rehabilitation\u003c/strong\u003e\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003ePrevious work with chronic conditions has suggested that using digital health platforms can improve outcomes.(16,17) These platforms usually have a patient facing app and a clinician facing dashboard and allow personalization of information and resources to the user; the tracking of symptoms, often assisted by the smartphone\u0026rsquo;s biometric sensors; contain educational resources; allow for goal setting and monitoring; facilitate collaborative care; and, create a connection between the patient and their clinician.(18) Although the size of the effect varies by condition and intervention(16,17), these platforms are often low burden to disseminate and adaptable to individual schedules, and may increase access to specialized care to patients across rural and remote regions. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDespite the explosion in e-health and coaching platforms available, a recent systematic review found there were few high quality trials examining the effectiveness of the intervention or its individual components.(19) These platforms have been used across multiple disorders including diabetes(20\u0026ndash;22), mental health(23\u0026ndash;25) and cancer recovery.(26,27) These e-health platforms also offer the opportunity for improved communication between the patient, caregivers and care providers, increasing both understanding of and adherence to treatment protocols.(18,25,28,29) In the case of Long COVID, the addition of a case management platform may prove particularly beneficial. As information is changing rapidly, patients may have more questions about their health concerns and their treatment plan. With electronic case management, clinicians can readily push new resources and information to patients and offer caregivers a more meaningful role.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003e\u003cstrong\u003e1.3 Rationale\u003c/strong\u003e\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe most comprehensive relevant guideline regarding Long COVID is the NICE \u0026ldquo;COVID-19 rapid guideline; managing the long-term effects of COVID-19\u0026rdquo; published in December 2020.(7) The guideline made key recommendations for research including \u0026ldquo;What is the clinical effectiveness of different service models of multimodality/multidisciplinary post-COVID-19 syndrome rehabilitation in improving patient-reported outcomes (such as quality of life)\u0026rdquo;. The NICE guideline also recommended that patients use symptom diaries or a tracking app to monitor their goals, recovery and any changes in their symptoms. This proposal directly addresses this recommendation, as the NICE guidelines provide no research to support this approach.(7) We aim to utilize these recommendations to evaluate what possible service models incorporating electronic case management (ECM) will improve outcomes in this population. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives {7}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003ePrimary Objective\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe primary objective of this trial is to determine if adding ECM with health coaching to usual care improves participant quality of life after three months for patients who present to hospital outpatient clinics experiencing Long COVID. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe hypothesize that adding ECM with health coaching to usual care will improve outcomes at three months compared to usual care alone.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eSecondary Objectives\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe key secondary objectives of this study are to determine:\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e1) the cost-effectiveness of adding ECM to usual care for Long COVID patients; 2) what factors predict outcomes at 3 months in patients with Long COVID; 3) if the addition of ECM affects Long COVID symptoms; and 4) how a personalized rehabilitation program supported by a digital platform could be implemented for individuals with Long COVID.\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe hypothesize that adding ECM to usual care will be cost-effective from a public-payer\u0026rsquo;s perspective. We also hypothesize that people with Long COVID who had severe acute COVID infections, or adverse childhood experiences or recent negative life events, or a strong sense of injustice at baseline will have poorer outcomes at 3 months. Lastly, we hypothesize that those with ECM will show more improvement across outcome measures at 12 weeks.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFollowing the Medical Research Council guidance on developing and evaluating complex interventions (30) we will conduct a process evaluation guided by the RE-AIM implementation framework.(31)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial design {8}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe proposed study is a 12-month open label, parallel group, randomized controlled trial. Participants will be allocated 1:1 into either electronic case management (ECM) with health coaching plus usual care or health coaching plus usual care alone. Due to the nature of the of the intervention, it will not be possible to blind clinicians or patients to the allocation.\u003c/p\u003e"},{"header":"Methods: Participants, interventions and outcomes","content":"\u003cp\u003e\u003cstrong\u003eStudy setting {9}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis single-site study will be conducted at the Ottawa Hospital Research Institute (OHRI). Recruitment will occur through two different streams to increase the diversity of participants. The first stream is a clinic that sees Ontario workers who were infected by SARS-CoV-2 at their worksite, who have made a claim to the Ontario Workplace Safety and Insurance Board (WSIB) and are assessed by the Ontario Workers Network (OWN) based at The Ottawa Hospital (TOH). The second stream are clinics within TOH which are seeing patients with Long COVID. These are clinics specifically for people with Long COVID, for example within the rehabilitation service, or specialist clinics that are seeing people with Long COVID such as respirology, infectious diseases or psychiatry. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEligibility criteria {10}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants will be recruited from TOH. Participants will be approached by an individual in their circle of care if they meet the eligibility criteria outlined in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1. Eligibility Criteria\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003eInclusion Criteria\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003eParticipants must:\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"4.216867469879518%\"\u003e\n \u003cp\u003e1.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"95.78313253012048%\"\u003e\n \u003cp\u003eBe 18 years of age or older\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"4.216867469879518%\"\u003e\n \u003cp\u003e2.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"95.78313253012048%\"\u003e\n \u003cp\u003eHave a confirmed diagnosis of COVID-19 with a PCR test at least 12 weeks prior OR a confirmed Rapid Antigen Test at least 12-weeks prior OR meet Ottawa Public Health guidance for a suspected COVID-19 case (Table 2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"4.216867469879518%\"\u003e\n \u003cp\u003e3.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"95.78313253012048%\"\u003e\n \u003cp\u003eHave at least one ongoing symptom consistent with Long COVID as measured by the WHO Post COVID Case Report Form (CRF)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"4.216867469879518%\"\u003e\n \u003cp\u003e4.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"95.78313253012048%\"\u003e\n \u003cp\u003eHave a minimum WHO Disability Assessment Scale (WHODAS) self-report (36 item) sum score of 15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"4.216867469879518%\"\u003e\n \u003cp\u003e5.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"95.78313253012048%\"\u003e\n \u003cp\u003eBe willing to use email for study activities\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"4.216867469879518%\"\u003e\n \u003cp\u003e6.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"95.78313253012048%\"\u003e\n \u003cp\u003eBe able and willing to use an electronic platform, either on smartphone or computer web browser, for the duration of the trial\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"4.216867469879518%\"\u003e\n \u003cp\u003e7.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"95.78313253012048%\"\u003e\n \u003cp\u003eBe able to read and understand English or French.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"4.216867469879518%\"\u003e\n \u003cp\u003e8.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"95.78313253012048%\"\u003e\n \u003cp\u003eBe willing and able to provide informed consent.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003eExclusion Criteria\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003eParticipants must not:\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"4.216867469879518%\"\u003e\n \u003cp\u003e1.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"95.78313253012048%\"\u003e\n \u003cp\u003eHave any significant functional impairment (for example. advanced dementia, heart or lung disease) as judged by the assessing clinician\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"4.216867469879518%\"\u003e\n \u003cp\u003e2.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"95.78313253012048%\"\u003e\n \u003cp\u003eParticipate in another long-COVID trial where treatment is required in the protocol (pharmacological or behavioural). Observational studies will be allowed.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"4.216867469879518%\"\u003e\n \u003cp\u003e3.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"95.78313253012048%\"\u003e\n \u003cp\u003eHave symptoms consistent with Long COVID that are better explained by an alternative diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003cem\u003eCOVID-19 Testing Eligibility\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eEffective December 30\u003csup\u003eth\u003c/sup\u003e, 2021 the government of Ontario significantly restricted the eligibility for PCR testing. The general public is no longer eligible for symptomatic PCR testing (\u003ca href=\"https://news.ontario.ca/en/backgrounder/1001387/updated-eligibility-for-pcr-testing-and-case-and-contact-management-guidance-in-ontario\"\u003ehttps://news.ontario.ca/en/backgrounder/1001387/updated-eligibility-for-pcr-testing-and-case-and-contact-management-guidance-in-ontario\u003c/a\u003e). Rapid Antigen Tests (RAT) are also significantly limited in Ontario and these results are not officially reported to any health agency. Additionally, in early 2020 testing was unavailable or highly limited. A previously approved, but not implemented, version of this protocol limited eligibility to PCR test only. To ensure that we are able to enroll individuals, inclusion criteria for testing will not be limited to PCR. The preferred confirmation of eligibility will remain a PCR test 12 weeks prior. Second line of eligibility confirmation will be a positive RAT 12 weeks prior. Third line will be for the participant to confirm a suspected case of COVID-19 indicating they were experiencing symptoms at least 12 weeks prior. Determination of a suspected case will follow the Ottawa Public Health Guidelines (\u003ca href=\"https://www.ottawapublichealth.ca/en/public-health-topics/resources/Documents/Self-Isolation-Flowchart_EN.pdf\"\u003ehttps://www.ottawapublichealth.ca/en/public-health-topics/resources/Documents/Self-Isolation-Flowchart_EN.pdf\u003c/a\u003e) summarized in Table 2.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Suspected COVID-19 Eligibility Criteria\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"46.53284671532847%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIf you experienced one of:\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"53.46715328467153%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIf you experienced two or more of:\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"46.53284671532847%\"\u003e\n \u003cp\u003eFever/Chills\u003c/p\u003e\n \u003cp\u003eCough\u003c/p\u003e\n \u003cp\u003eShortness of Breath\u003c/p\u003e\n \u003cp\u003eDecrease/Loss of Smell or Taste\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"53.46715328467153%\"\u003e\n \u003cp\u003eSore Throat\u003c/p\u003e\n \u003cp\u003eHeadache\u003c/p\u003e\n \u003cp\u003eRunny Nose/Nasal Congestion\u003c/p\u003e\n \u003cp\u003eExtreme Fatigue\u003c/p\u003e\n \u003cp\u003eMuscle/Joint Pains\u003c/p\u003e\n \u003cp\u003eGI Symptoms (Vomiting, Diarrhea)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;Potential Participants will be asked to confirm that symptoms were a minimum of twelve weeks ago and the delegated research staff will document the date and the list of symptoms experienced. The Principal Investigator will then make the final determination about inclusion in the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAccess to Technology\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eParticipants are not required to have a smartphone with a data plan in order to participate in the intervention arm. Participants will be able to access their patient dashboard from their computer or tablet with internet access. Participants who do not have any available options to access the platform and are randomized to the intervention arm will be provided with one pre-paid smartphone with voice and data services for the duration of their study participation. Provision of a second phone in the event of loss or theft will be evaluated on a case-by-case basis.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWho will take informed consent? {26a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll informed consent discussions will be completed by a site-delegated study staff member, such as a research coordinator or research assistant.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional consent provisions for collection and use of participant data and biological specimens {26b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs per Institutional guidelines, participants will be asked to complete a \u0026ldquo;Consent to Communicate by Email\u0026rdquo; form prior to completing the informed consent discussion. Participants will be asked permission to share their de-identified trial data in an open access database, in line with Canadian Institutes of Health Research (CIHR) best practice. This trial does not involve collecting biological specimens for storage.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInterventions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExplanation for the choice of comparators {6b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUtilizing the NICE COVID-19 treatment guideline, we have selected a comparator group that will be able to answer the question \u0026ldquo;What is the clinical effectiveness of different service models of multimodality/multidisciplinary post-COVID-19 syndrome rehabilitation in improving patient-reported outcomes (such as quality of life)\u0026rdquo;. The comparator group will receive usual care and health coaching as required. We chose to compare this to health coaching plus electronic case management in the intervention group as this addresses one of the recommended research questions in the NICE guidelines \u003cem\u003e\u0026ldquo;\u003c/em\u003e\u003cem\u003eWhat is the clinical effectiveness of different service models of multimodality/multidisciplinary post‑COVID‑19 syndrome rehabilitation in improving patient‑reported outcomes (such as quality of life)?\u0026rdquo;\u003c/em\u003e .\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntervention description {11a}\u003c/strong\u003e\u003cbr\u003e\u003cem\u003eControl Arm: Health Coaching Plus Usual Care\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAssessment.\u003c/u\u003e Participants randomized to the control arm will be offered assessment by a clinician, guided by the WHO Post COVID-19 CRF (\u003ca href=\"https://www.who.int/publications/i/item/global-covid-19-clinical-platform-case-report-form-(crf)-for-post-covid-conditions-(post-covid-19-crf-)\"\u003ehttps://www.who.int/publications/i/item/global-covid-19-clinical-platform-case-report-form-(crf)-for-post-covid-conditions-(post-covid-19-crf-)\u003c/a\u003e. This is a clinical tool developed by the WHO to guide and document the sequelae of COVID-19 and to ensure that clinical and rehabilitation needs are identified.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eInvestigation.\u003c/u\u003e Clinician judgement will be used to decide on further testing needed for clinical care.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eManagement.\u003c/u\u003e Control participants will receive a rehabilitation plan developed with their health professional that will be implemented in the eight weeks after their initial consultation (baseline visit) and access to a personal health coach. The implementation will involve face to face or virtual care from a registered health professional provided by the clinic or research staff. This may be a combination of, but not limited to, occupational therapy, physical therapy and/or social work/counselling services. The frequency of treatment visits will depend on the individual treatment plan after assessment. All participants will receive access to a health coach.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eExperimental Arm: Electronic Case Management Plus Usual Care\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eParticipants randomized to the experimental arm will receive assessment, investigation and management as outlined in 3.4.1 (Control) plus access to an electronic case management platform \u0026ndash; NexJ Connected Wellness (\u003ca href=\"https://nexjhealth.com/\"\u003ehttps://nexjhealth.com/\u003c/a\u003e), supported by a personal health coach and which complements the rehabilitation plan. This would include, for example, setting targets for activity that would be monitored with NexJ; educational materials; and support with medication adherence by reminders. The design of the application is outlined in Appendix 4. The NexJ platform will include the following sections: Case Plans with Educational Workbooks, Trusted Educational Content (Health Library), Symptom Tracking, Goal Setting and Reporting.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTiming of Sessions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll participants will receive health coaching sessions up to once a week. Participants who are using NexJ will have assigned content between sessions. Due to the heterogeneous nature of Long-COVID presentation, timing of clinical rehabilitation sessions will be individualized based on the treatment plan. This information will be recorded for each participant.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCriteria for discontinuing or modifying allocated interventions {11b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDecisions about modifying individual rehabilitation care or health coaching will be made in collaboration with the most responsible healthcare provider and the Principal Investigator. No predefined criteria will be used with respect to modifying individual interventions. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe trial will be stopped if more than 25% of participants in the intervention group experience at least a 20% increase in severity in their WHODAS sum score. There will be no stopping criteria for benefit given the short duration of the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrategies to improve adherence to interventions {11c}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo particular strategy will be implemented to improve adherence to the intervention as this is an outcome of the study. As part of the process evaluation, we are examining factors affecting adherence to the intervention. We will evaluate any differences in adherence between the treatment and intervention groups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRelevant concomitant care permitted or prohibited during the trial {11d}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs outlined in Table 1, only other trials providing treatment for Long COVID will be prohibited. All other concomitant care is permitted and will be documented.\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;Provisions for post-trial care {30}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the event of a study-related injury or illness, participants will be provided with appropriate medical treatment and care. Financial compensation for lost wages, disability, or discomfort due to an injury or illness is not generally available. After study completion, participants will not have access to the NexJ Connected Wellness platform as this is not publicly available. The participants\u0026rsquo; most responsible care provider will ensure a transition back to or continuation of standard care, as required.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcomes {12}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePrimary Outcome\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eTo evaluate the primary outcome, improvement in quality of life, we will use the total sum score of the WHO Disability Assessment Scale (WHODAS 2.0) self-assessment. The WHODAS is the 36-item self-report questionnaire measuring health and disability from the previous 30 days across six domains of functioning: cognition, mobility, self-care, getting along, life activities and participation. Responses are scored on a 5 point Likert scale: None [0], Mild [1], Moderate [2], Severe [3], and Extreme/Cannot Do [4].(32)\u003c/p\u003e\n\u003cp\u003eThe WHODAS 2.0 has been validated using a cross-cultural approach in 19 countries and within 4 subgroups (general population, populations with physical problems, populations with mental or emotional problems, and populations with problems related to substance use). The WHODAS 2.0 showed excellent overall test-retest reliability (ICC=0.98) and internal consistency (Cronbach\u0026rsquo;s alpha= 0.98). The survey also showed good cross-cultural sensitivity and concurrent validity.(32)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003e3.5.2 Secondary Outcomes\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eLong COVID Characteristics\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eTo describe the population and their experience with Long COVID, we will administer the WHO Post COVID Case Report Form (CRF) Modules 1,2 and 3 at baseline and only Module\u0026rsquo;s 2 and 3 at 12 weeks.(33)\u0026nbsp;The CRF Module 1 captures demographics, pregnancy, pre-COVID health status, and details about the acute COVID infection. CRF Modules 2 and 3 collect vaccination status, occupational status, functioning, post-COVID symptoms, clinical tests and scales (including neurological, radiographic, blood tests, heart and lung function, mental health, function, and musculoskeletal tests), new diagnoses or complications related to COVID infection, and health service use, symptoms.(33)\u0026nbsp;The CRF will be completed using health record review whenever possible, with missing information completed by interview with the participant.\u003c/p\u003e\n\u003cp\u003eCurrently, little is known about the long-term consequences of infection with COVID-19. In response to this, the WHO has created the WHO Post COVID Case Report Form, which will allow health care providers internationally to collect information on COVID-19 systematically. The use of this CRF will allow for the trial dataset to be aligned with the global WHO Clinical Platform and contribute to expanding our knowledge on Post-COVID-19 condition(s).\u003c/p\u003e\n\u003cp\u003eAll other secondary outcome measures are described in Table 3.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Secondary Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.399193548387096%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMeasure\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.306451612903226%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDescription\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"74.29435483870968%\"\u003e\n \u003cp\u003e\u003cstrong\u003eProperties\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" width=\"12.399193548387096%\"\u003e\n \u003cp\u003eCognitive Testing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.306451612903226%\"\u003e\n \u003cp\u003eExecutive function, Visual attention, Task switching\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"74.29435483870968%\"\u003e\n \u003cp\u003eThe Oral Trail Making Test (O-TMT) (versions A and B) will be used to evaluate executive function, visual attention and task switching in participants. During O-TMT A, participants will be asked\u0026nbsp;to count out loud from 1 to 25 and is primarily a measure of processing speed and simple attention. During O-TMT B, participants will be asked\u0026nbsp;to alternate saying numbers and letters (1-A, 2-B, etc.) and is a measure of mental flexibility. Time to completion as well as total errors are recorded\u0026nbsp;(34,35).\u0026nbsp;The use of time and error rate led to slightly improved classification rates for cognitive impairments compared to either alone.(36)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.189873417721518%\"\u003e\n \u003cp\u003eVerbal learning and memory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"84.81012658227849%\"\u003e\n \u003cp\u003eThe Hopkins Verbal Learning Test-Revised (HVLT-R) will be used to evaluate verbal learning and memory capabilities in participants.(37)\u0026nbsp;The HVLT consists of a 12-item word list, composed of four words from each of three semantic categories. The list is read to participants at a rate of approximately 2 words per second. Participants are then asked to free recall the list of words. This is repeated for 3 trials. After the third trial and a 20-25 minute delay (with no forewarning), participants will again be asked to free recall the 12 words and then will be read 24 words and asked to say \u0026ldquo;yes\u0026rdquo; after each word that appeared on the recall list (12 targets) and \u0026ldquo;no\u0026rdquo; after each word that did not (12 distractors).(38)\u0026nbsp;The HVLT is available in 6 forms to reduce test-retest learning effects, takes no more than 10 minutes to administer and is shown to be well tolerated by participants.(37)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.189873417721518%\"\u003e\n \u003cp\u003eAttention, Working memory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"84.81012658227849%\"\u003e\n \u003cp\u003eThe Digit Span subset, a component of the Working Memory Index of the Weschler\u0026rsquo;s Adult Intelligence Scale \u0026nbsp;- 4\u003csup\u003eth\u003c/sup\u003e Edition (WAIS-IV), will be used to assess attention and working memory.(39)\u0026nbsp;Participants will be read a series of numbers and then asked to recall the numbers to the examiner in order (forward span), in reverse order (backward span) and in sequence (sequence span). Participants will complete spans of increasing length, with two trials at each length, until an error is made on both trials of a given length. Digit Span has shown good internal consistency and test-retest reliability across age groups.(39,40)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.189873417721518%\"\u003e\n \u003cp\u003eVerbal fluency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"84.81012658227849%\"\u003e\n \u003cp\u003eThe Phonemic and Semantic Verbal Fluency (or Controlled Oral Word Association Test [COWAT]) test will be used to assess verbal fluency. Participants will be given one minute to produce as many unique words as possible: 1) within a semantic category (category fluency for Animals); and 2) starting with a given letter (letter fluency for letters F, A and S). The COWAT has been shown to have sensitivity to brain lesions and conditions with impaired cognition (e.g., traumatic brain injury). Population norms are available for the COWAT for a broad age (16-95) and education (0-21 years).(41,42)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.399193548387096%\"\u003e\n \u003cp\u003ePHQ-9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.306451612903226%\"\u003e\n \u003cp\u003eDepression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"74.29435483870968%\"\u003e\n \u003cp\u003eA 9-item questionnaire that assesses the severity of depression symptoms experienced within the last two weeks. Participants are asked to rate each symptom of depression on a Likert scale from 0 (not at all) to 3 (nearly every day), with total scores ranging from 0 (minimal depression) to 27 (severe depression). The PHQ-9 has strong methodological properties with an internal consistency of 0.89 and strong test re-test reliability.(43)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.399193548387096%\"\u003e\n \u003cp\u003eGAD-7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.306451612903226%\"\u003e\n \u003cp\u003eAnxiety\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"74.29435483870968%\"\u003e\n \u003cp\u003eA 7-item questionnaire that assesses the severity of anxiety symptoms experienced within the last two weeks. The initial validation study, conducted by Spitzer et al. (2006), demonstrated high internal consistency (\u0026alpha;=0.92) and test-retest reliability (intraclass correlation = 0.83).(44)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.399193548387096%\"\u003e\n \u003cp\u003ePSQI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.306451612903226%\"\u003e\n \u003cp\u003eSleep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"74.29435483870968%\"\u003e\n \u003cp\u003eThe Pittsburgh Sleep Quality Index (PSQI) is a self-report questionnaire that assesses sleep quality in the previous month and takes 5-10 minutes to complete. It has been translated into over 50 languages. Using a threshold score of greater than 5, the PSQI showed a diagnostic sensitivity of 89.6% and specificity of 86.5% (kappa = 0.75, p \u0026lt; 0.001) in distinguishing \u0026ldquo;good\u0026rdquo; and \u0026ldquo;poor\u0026rdquo; sleepers.(45)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.399193548387096%\"\u003e\n \u003cp\u003ePSTD Checklist 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.306451612903226%\"\u003e\n \u003cp\u003ePost-Traumatic Stress Disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"74.29435483870968%\"\u003e\n \u003cp\u003eA 20-item self-report measure that assesses the presence and severity of PTSD symptoms, corresponding with DSM-5 criteria for PTSD. PCL-5 scores exhibit strong internal consistency (\u0026alpha; = .94), test-retest reliability (r = .82), and convergent (rs = .74 to .85) and discriminant (rs = .31 to .60) validity.(46)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.399193548387096%\"\u003e\n \u003cp\u003eEQ-5D-5L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.306451612903226%\"\u003e\n \u003cp\u003eQuality of\u003c/p\u003e\n \u003cp\u003eLife\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"74.29435483870968%\"\u003e\n \u003cp\u003eThis is a 5-item questionnaire that assesses health-related quality of life, including mobility, self-care, ability to participate in one\u0026rsquo;s usual activities, pain or discomfort, and anxiety or depression and a Visual Analogue Scale (VAS) which asks participants to evaluate their overall health on a scale from 0-100. It is available in multiple languages and there are standardised scores for patient populations in different settings. The EQ-5D-5L is able to define a unique health state based on the responses to each of the five dimensions of health described above.(47)\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.399193548387096%\"\u003e\n \u003cp\u003eAUDIT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.306451612903226%\"\u003e\n \u003cp\u003eAlcohol Use\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"74.29435483870968%\"\u003e\n \u003cp\u003eThe AUDIT questionnaire is designed to assess alcohol consumption, drinking behavior, adverse reactions, and alcohol-related problems. Among those who were known to misuse alcohol, the AUDIT successfully detected an alcohol use disorder 99% of the time\u0026nbsp;(48).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.399193548387096%\"\u003e\n \u003cp\u003eASSIST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.306451612903226%\"\u003e\n \u003cp\u003eAlcohol and Substance Use\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"74.29435483870968%\"\u003e\n \u003cp\u003eThe ASSIST is a brief interview collecting information regarding use of tobacco, alcohol, cannabis, cocaine, amphetamine type stimulants, sedatives, hallucinogens, inhalants, opioids, and other drugs. Internal Consistency (Chronbach\u0026rsquo;s alpha) was over 0.80 for the majority of domains and good concurrent validity(49,50).\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.399193548387096%\"\u003e\n \u003cp\u003eFSS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.306451612903226%\"\u003e\n \u003cp\u003eFatigue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"74.29435483870968%\"\u003e\n \u003cp\u003eThe Fatigue Severity Scale is a 9-item self-report that measures the severity and functional\u0026nbsp;impact of fatigue. The scale demonstrated good internal consistency (Cronbach\u0026rsquo;s\u0026nbsp;\u0026alpha;\u0026nbsp;0.88), as well good test-retest reliability and sensitivity to clinical change.(51)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.399193548387096%\"\u003e\n \u003cp\u003eFatigue Numeric\u003c/p\u003e\n \u003cp\u003eRating Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.306451612903226%\"\u003e\n \u003cp\u003eFatigue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"74.29435483870968%\"\u003e\n \u003cp\u003eA single item patient reported outcome, scored on a scale of 0-10, with good test-retest\u0026nbsp;reliability (ICC=0.79, p \u0026lt; 0.008) and sensitivity to change.(52)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.399193548387096%\"\u003e\n \u003cp\u003ePain Numeric Rating Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.306451612903226%\"\u003e\n \u003cp\u003ePain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"74.29435483870968%\"\u003e\n \u003cp\u003eThe Pain Numeric Rating Scale will be used to assess pain intensity using a 0\u0026ndash;10 ranking scale, where 0 represents \u0026ldquo;no pain\u0026rdquo; and 10 \u0026ldquo;unbearable pain\u0026rdquo;. The scale shows good test-retest reliability (ICC=0.72 for single item), and sensitivity(53). Pain may be categorized using Mild (scores \u0026le;5), Moderate (scores 6-7) or Severe (scores \u0026ge;8).(54)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.399193548387096%\"\u003e\n \u003cp\u003eMRC Dyspnoea\u003c/p\u003e\n \u003cp\u003eScale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.306451612903226%\"\u003e\n \u003cp\u003eBreathlessness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"74.29435483870968%\"\u003e\n \u003cp\u003eA 5-item self report scale that evaluates statements of perceived breathlessness. The scale has\u0026nbsp;good correlation to level of disability due to breathlessness.(55)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.399193548387096%\"\u003e\n \u003cp\u003eWEMWBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.306451612903226%\"\u003e\n \u003cp\u003eWellbeing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"74.29435483870968%\"\u003e\n \u003cp\u003eThe Warwick Edinburgh Mental Wellbeing Scale (WEMWBS) (short version) is a 7-item scale which measures multiple aspects of mental wellbeing(56). It has been validated in general population samples and in English and French(57), and is sensitive to change.(58)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003ePredictors and Potential Confounders\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAt the first assessment we will collect information on potential predictors and potential confounders as listed in Table 4. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. Predictors, potential confounders and effect modifiers\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePredictors and potential confounders\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.495726495726494%\"\u003e\n \u003cp\u003eDemographic details\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"73.5042735042735%\"\u003e\n \u003cp\u003eAt baseline, we will collect information on ethnicity, gender identity, education, income, employment, housing and living circumstances\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.495726495726494%\"\u003e\n \u003cp\u003ePast medical history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"73.5042735042735%\"\u003e\n \u003cp\u003eThis will include body mass index and past medical and mental health disorders\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.495726495726494%\"\u003e\n \u003cp\u003eImpact of COVID-19 infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"73.5042735042735%\"\u003e\n \u003cp\u003eFor those who tested positive we will record details of the severity and impact of the COVID-19 infection including neurological symptoms such as anosmia and headaches, length of time self-isolating and time off work\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.495726495726494%\"\u003e\n \u003cp\u003eIEQ-SF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"73.5042735042735%\"\u003e\n \u003cp\u003eThe Injustice Experience Questionnaire (IEQ) is a 12-item self-report that assesses perceived injustice\u0026nbsp;associated with injury. The IEQ showed good correlation with measures of catastrophic thinking (r=.75, p \u0026lt;.01), fear of movement/re-injury (r=.58, p\u0026lt;.01), depression (r=.66, p\u0026lt;.01), and pain severity (r=.54, P\u0026lt;.01).The IEQ also demonstrated good test-retest reliability.(59)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.495726495726494%\"\u003e\n \u003cp\u003eAdverse childhood events questionnaire (ACE)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"73.5042735042735%\"\u003e\n \u003cp\u003eThe ACE-Q is a 17 item self-report questionnaire assessing types of adverse exposures during childhood including psychological, physical and sexual abuse as well as household dysfunction. The ACE questionnaire study found strong relationships between childhood exposure and disease conditions, health risk factors and a strong dose-response relationship between number of exposures and risk factors for death.(60)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003cem\u003eProcess Evaluation\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eTo inform the implementation of the intervention beyond the clinical trial and describe the intervention process we will use the RE-AIM framework.(31)\u0026nbsp;We will assess Reach by recording what proportion of eligible patients participate in the trial and comparing characteristics of participants to non-participants. Effectiveness will be assessed in the clinical trial and separately stratified by sex. We will also record dropouts by sex and severity. We will conduct qualitative interviews with participants to better understand the reasons for participating, the experience of using the NexJ app and any reasons for drop out. We will use a thematic analysis and aim to complete at least 20 user interviews and will continue until we achieve data saturation.\u0026nbsp;We will gather usage data from NexJ.\u0026nbsp;Adoption at the setting level will be assessed by comparing uptake in the different clinics supplemented by qualitative interviews of clinical staff. Adoption at the staff level will compare high referrers to the study to low\u0026nbsp;referrers and doing qualitative interviews with staff in each group. Implementation will be assessed with a study specific-adherence scale. Maintenance at an individual and setting level will be assessed using the Consolidated Framework for Implementation Research (CFIR) to inform qualitative interviews with key stakeholders to identify barriers and facilitators to introducing NexJ in outpatient clinics.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEconomic Evaluation\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe will conduct a cost-utility analysis of an electronic case management system compared with usual care from a perspective of the publicly funded health care system. Costs and outcomes will be assessed within the follow up period of the trial. Resources and associated costs required to set up and operate a unique instance of the NexJ platform will be estimated from the budget review and staff interview. We will collect health care utilization data, such as hospitalization, emergency department visits, physician visits, prescriptions, and the efficacy of the intervention, from the concurrent trials. We will derive health utility value from the EQ-5D-5L using the Canadian validated algorithm.(61)\u0026nbsp;Quality-adjusted life years (QALYs) will be estimated using the total area under the curve method.(62)\u0026nbsp;Unit costs for each health care resource will be obtained from Canadian Sources. Costs will be expressed in 2021 Canadian Dollars.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipant timeline {13}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAdministration will occur as per Time and Events Schedule in Table 5. Clinical visits will occur as needed and will be determined during the initial assessment. Clinical visits are not outlined in the time and event schedule as these are a part of routine care. Self-report measures will be completed at home prior to each study visit using the study electronic data capture system (EDCS). Participants will be able to leave and return to the questionnaires whenever they need to complete them. It is anticipated the first and last visit will take approximately 45 minutes, while week 4 and 8 will take approximately 30 minutes. Participants will complete the WHODAS first and all responses are mandatory. All other self-report measures will be completed in a structured order.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5. Time and Events Schedule\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMeasures\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime to Complete (Minutes)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.42056074766355%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdministration\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeek 4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeek 8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeek 12\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003eWHO Post COVID CRF Module 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eChart Review\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003eWHO Post COVID CRF Module 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eChart Review\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003eWHO Post COVID CRF Module 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eChart Review\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003eDemographics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003e\u0026lt;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eSelf-Report\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003eACE-Q\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eSelf-Report\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003eInjustice\u0026nbsp;Experience\u0026nbsp;Questionnaire (IEQ-SF)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003e\u0026lt;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eSelf-Report\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003eWHODAS (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eSelf-Report\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003ePHQ-9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003e\u0026lt;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eSelf-Report\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003eGAD-7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003e\u0026lt;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eSelf-Report\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003ePCL-5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eSelf-Report\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003eEQ-5D-5L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003e\u0026lt;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eSelf-Report\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003eAUDIT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003e\u0026lt;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eSelf-Report\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003eASSIST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003e5-10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eInterview\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003eFatigue Severity Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003e\u0026lt;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eSelf-Report\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003ePSQI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eSelf-Report\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003eWarwick Edinburgh Mental Wellbeing Scale (WEMWBS)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.74766355140187%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eSelf-Report\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003ePain Numeric Rating Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003e\u0026lt;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eSelf-Report\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003eMRC Dyspnoea Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003e\u0026lt;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eSelf-Report\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003eCognition (Trailmaking, Hopkins Verbal Learning, Digit Span, Phonemic/Semantic Verbal Fluency)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.74766355140187%\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eInterview\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.64485981308411%\"\u003e\n \u003cp\u003eQualitative Interview (Optional)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.74766355140187%\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.42056074766355%\"\u003e\n \u003cp\u003eInterview\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.968847352024921%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.034267912772586%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.59190031152648%\"\u003e\n \u003cp\u003e\u003cstrong\u003eX\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample size {14}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe have based the sample size calculation on the sum of domain scores of the WHODAS 36, as the recommended assessment for Long COVID patients.(33)\u0026nbsp;At the time of writing this protocol, there were no published scores of the WHODAS 36 in people with Long COVID. Therefore, we have based our sample size calculation on WHODAS 36 scores from 25 randomly selected patients attending an existing clinic for Long COVID at TOH run by OWN. These patients had a mean sum of domain scores of 17 (SD=4). The minimally important clinical difference on the WHODAS is about a 10% change in scores.(32)\u0026nbsp;Using these assumptions, we need to recruit at least 126 participants (63 in each group) to have 80% power to detect a 10% change in scores assuming an alpha of 0.05. Allowing for 20% drop out would mean a recruitment target of 152 (76 in each group) people.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRecruitment {15}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants will be recruited at TOH through two potential recruitment streams. The first clinic sees Ontario workers who were infected by SARS-CoV-2 at their worksite, who have made a claim to the Ontario WSIB and are assessed by the OWN based at TOH. The second stream is any clinics within TOH which are seeing patients with Long COVID. These are either clinics specifically for people with Long COVID, for example within respirology, infectious diseases or psychiatry. The anticipated flow of recruitment is outlined in Figure 1 below.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssignment of interventions: Allocation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSequence generation {16a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRandomization will be done remotely by the Ottawa Methods Centre (OMC) through an electronic randomization system. Participants will be randomized at enrollment by a delegated study staff member. As participants are created in the electronic data capture system (EDCS), they are automatically randomized. The delegated study staff member will be informed of the allocation at the time of randomization.\u003c/p\u003e\n\u003cp\u003eAllocation will be a 1:1 ratio into the treatment arms. Participants will be stratified by sex and duration of symptoms. The reasons for stratification by sex are that the mortality rate in males is higher than in females and that outcomes may be affected by gendered occupations.(63\u0026ndash;66)\u0026nbsp;We will stratify by the duration of symptoms into two groups: (1) those who at enrolment have had symptoms since the onset of their index illness for 12 to 23 weeks, and (2) those who have had symptoms at enrolment for 24 weeks or longer, which is consistent with the classification of Long COVID in the NICE guidelines. We are stratifying for duration of illness as this is one of the main determinants of outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConcealment mechanism {16b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. Since the interventions are assigned through random computer generation, allocations are not visible in advance, and no concealment is required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImplementation {16c}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOnce participants have consented and completed screening determining eligibility, they will be registered in the study electronic data capture and randomization system by the delegated research staff member. Once the participant is registered, the system will automatically allocate the participant to the intervention. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssignment of interventions: Blinding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWho will be blinded {17a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDue to the nature of the intervention, a behavioural intervention where both patient and clinician must use an electronic platform, it is not possible to blind either group to their allocation. Data analysts and manuscript writers will be blind to the identity of the two groups which will be referred to as group A and group B. Once initial manuscript preparation is complete, the groups will be unblinded. We will also assess potential bias in recruitment during an interim analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eProcedure for unblinding if needed {17b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable \u0026ndash; all participants and treating clinicians are unblinded to the intervention.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection and management\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans for assessment and collection of outcomes {18a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll self-reported outcome measures will be administered via the EDCS for all study visits. Interview measures, when done remotely, will be completed using a videoconferencing platform. Information from the WHO Post-COVID Assessment CRF will be entered by delegated study staff into the EDCS.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCognitive assessments will be administered by a trained research staff member. The delegated study staff member will receive direct training from an experienced Psychologist, including rehearsal and independent evaluation, prior to administration with participants.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans to promote participant retention and complete follow-up {18b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA major difficulty in all clinical research is ensuring participants attend their visits and stay enrolled in the study. Efforts will be made to minimize the time between being approached about the study and the baseline visit. We anticipate lost to follow-up to be no more than 20%. While there is currently no available literature on the lost to follow up rates for Long COVID rehabilitation, the case management platform we are using has demonstrated significantly higher levels of retention in difficult to treat populations.(24) For those participants in the intervention arm, daily and weekly reminders will be programmed into the NexJ Connected Wellness platform to encourage regular use and increase connectedness with the platform, increasing retention. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe will implement an escalated approach if contact is lost with individuals between study visits. The appropriate response will be determined in collaboration with the Principal Investigator, particularly if there is a potential safety concern. If contact is made with the participant and they are no longer interested in participating, the delegated study staff member will make every effort to ascertain why they are withdrawing their consent. Participants will be sent the link to complete their self-report questionnaires at each time point unless they have withdrawn their consent for participation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData management {19}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll study outcome data will be directly entered into an EDCS. Data will be automatically coded and the code will be described using a data dictionary. Range checks will be included for illogical entries. Missing items will be flagged for self-entry, however, participants can bypass the warning. A delegated study staff member will follow-up on the missing entry to confirm if the question was missed or the participant is refusing to answer.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe EDCS is a username and password protected web-based system. All network, server security and privacy settings are regularly tested and comply with Health Canada recommendations and Good Clinical Practice (GCP) for secured data management services.(67,68) The EDCS is hosted on a physical server, not in the cloud, that is located at TOH data centre in a secure server room with limited access to authorized personnel behind lock doors. The web/database server is behind the TOH firewalls. The OHRI web site is secured with the highest rating from Entrust SSL virtual test. The data transfer between the client and server is protected with Entrust SSL 256-bit encryption. All data transfers between the client computers/browsers and the server/database are encrypted via https. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConfidentiality {27}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll records will automatically be assigned a unique Participant ID during randomization. The Participant ID will be recorded on a master linking log. The master linking log will be password protected and stored with limited access as per institutional policy. The Participant ID will appear on all documentation included in a participant\u0026rsquo;s research chart, including study forms and correspondence, in order to maintain participant confidentiality. All correspondence with participants will be de-identified, removing names and other potentially identifying information, prior to being included in the study chart. Some documentation will remain identifiable including the Informed Consent Form, the Participant Information Form and the Emergency Contact Form. These will not be stored with documentation identified with a Participant ID. Hard copy documentation will be stored in a double locked area (e.g. locked cabinet and secure office space). Study documents will be password protected and a log kept separately from the documents so that access to the files is not lost in the event of staff turnover or during the archiving period. Electronic documents will not be stored on mobile devices (such as a USB or directly on a laptop). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDocuments requiring de-identification must use an approved method. Electronic documents must be redacted so that the information removed cannot be recovered at a later time utilizing a tool such as Adobe Pro \u0026ldquo;Redact\u0026rdquo; feature, permanently obscuring the data. Hardcopy documentation will be redacted using only a \u0026ldquo;china marker\u0026rdquo;, which completely obscures the data. Sharpie, pen and other writing tools are not permitted as they do not permanently obscure/destroy the data. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eParticipants\u0026rsquo; study information will not be released unless a delegated study staff member obtains written permission from the participant or where required by law. Participants will not be identified in study presentations or publications. Once all study activities are complete all study records and data exports will be archived at a secure storage facility for a period of ten years, as per the applicable N2 SOP and GCP regulations. The ten-year period will begin from the date the last informed consent form is signed.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. There are currently no ancillary trials planned.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical methods for primary and secondary outcomes {20a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe OMC will complete all data analyses. Baseline characteristics will be presented as means (or medians) with associated measures of variation for continuous variables, or frequencies and proportions for categorical data. We will use an intention-to-treat analysis based on all randomized participants. Additionally, we will analyze the primary and secondary outcomes based on the treatment received. Analyses will utilize a GBA+ focused Health Equity Impact Assessment (HEIA)(69) approach to examine how sex and gender interact with socioeconomic status, age, race/ethnicity and rural/urban residence.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAnalysis of primary and secondary outcomes will use relative risks and mean differences and be calculated and presented with 95% CIs. We will include subgroup analyses of participants by age, sex, and severity of Long COVID. The effects of group (control vs. experimental), Long COVID severity, and adverse childhood events on the linear change over time in the primary outcome (measured at 4 time points) will be analyzed using hierarchical regression. Bivariate associations between primary and secondary outcomes (and among secondary outcomes) measured at baseline and at the end of the study will be estimated with Pearson correlation coefficients (or Spearman correlation coefficients for non-parametric data).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEconomic Evaluation\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eResults of a cost-utility analysis will be presented as incremental cost per QALY gained. The incremental cost and incremental outcome will be estimated using generalized linear models that explicitly allow for the modelling of normal and non-normal distributional forms of data. The incremental cost-effectiveness ratio will be obtained through the difference in the mean costs of the two strategies divided by the difference in the mean QALYs for each strategy as denoted by the coefficient of the intervention indicator variables. Uncertainty in the analysis will be addressed by estimating 95% confidence intervals using a non-parametric bootstrapping method. For this study, we will obtain 10,000 estimates of costs and outcomes for each strategy. Results from the bootstrapping exercise will also be used to show cost-effectiveness acceptability curves, which represent the probability of NexJ being cost-effective over a range of willingness to pay values that the health system may be willing to pay for an additional unit of QALY.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInterim analyses {21b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe will do a health equity impact assessment at six months to ensure the study has addressed potential health inequities in recruitment, treatment, and assessment using the Ontario Health Equity Impact Assessment (HEIA) tool.(69)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods for additional analyses (e.g. subgroup analyses) {20b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. There are currently no planned subgroup analyses.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEfforts will be made to minimize missing data, although it is possible that some amount of missing data may occur. We will examine the pattern of missing data by comparing characteristics of participants with missing data to those of participants with complete data to examine the assumption of Missing at Random. In the case of substantial missingness (e.g., \u0026gt;5%), missing covariates and outcomes will be imputed using multiple imputation with m=10 imputed data sets prior to analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans to give access to the full protocol, participant level-data and statistical code {31c}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Principal Investigator will retain ownership of the dataset through the 10-year archiving period. The protocol will be made available open-access and will be published, at a minimum, on an open-science platform such as Open Science Framework or medRXiv. The anonymized data set will be shared on an open science platform, such as Open Science Framework or Zenodo. The anonymized dataset may also be shared with the WHO to facilitate global post-COVID-19 research and treatment efforts.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOversight and monitoring\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComposition of the coordinating centre and trial steering committee {5d}\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.205128205128204%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCommittee\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"37.03703703703704%\"\u003e\n \u003cp\u003e\u003cstrong\u003eResponsibilities\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"34.75783475783476%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMembership\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.205128205128204%\"\u003e\n \u003cp\u003eTrial Steering Committee\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"37.03703703703704%\"\u003e\n \u003cp\u003eApproval of the final protocol; Reviewing and advise on progress of study; facilitation of study conduct; end point evaluation; manuscript coordination, knowledge translation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"34.75783475783476%\"\u003e\n \u003cp\u003eInvestigators as listed, other members as outlined in the Trial Steering Committee charter.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"28.205128205128204%\"\u003e\n \u003cp\u003eTrial Management Committee (Coordinating Centre responsibilities)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"37.03703703703704%\"\u003e\n \u003cp\u003eProtocol management, study documentation, ethics, contracts, study planning, day-to-day activities, budgets, monitoring, data verification, randomization, support study registered health professionals, investigator support for trial activities, liaise with platform service provider; organize steering committee meetings, implement steering committee action items\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"34.75783475783476%\"\u003e\n \u003cp\u003ePrincipal Investigator, co-Principal Investigator, Clinical Research Program Manager, Clinical Research Coordinator, Clinical Research Assistant\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComposition of the data monitoring committee, its role and reporting structure {21a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAn independent Data and Safety Monitoring Committee (DSMC) has been convened to assess the progress of the clinical trial, the integrity of the data, the safety of all participants and to provide recommendations to the Principal Investigator(s). The members of the DSMC serve in an individual capacity and provide their expertise and recommendations. The DSMC will review cumulative study data to evaluate safety, study conduct, scientific validity, and data integrity of the study. A charter will outline the full responsibilities of the DSMC. At a minimum, the general responsibilities of the DSMC will be:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eTo evaluate any reports of safety-related events in the study to ensure the ongoing safety of participants;\u003c/li\u003e\n \u003cli\u003eTo consider factors external to the study when relevant information becomes available, such as scientific or therapeutic developments that may have an impact on the safety of the participants or the ethics of the study;\u003c/li\u003e\n \u003cli\u003eTo review the conduct of the study;\u003c/li\u003e\n \u003cli\u003eTo make recommendations to continue, modify, or terminate the study.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eMembership will be comprised of four independent, interdisciplinary members. Possible fields of expertise include statistics/biostatistics, epidemiology, methodology, psychiatry and the ethics of clinical trials. Members will be identified in the DSMC charter.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdverse event reporting and harms {22}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipant well-being and safety will be monitored by the Investigators and Registered Health Professionals (RHPs), within the restrictions of their respective professional colleges. Adverse Events will be collected at each study visit. Standard operating procedures (SOPs) will be developed for escalation of participant safety concerns, for example by setting a threshold increase on mental health scales where the Principal Investigator, or appropriate most responsible care provider, is notified for follow-up. If a significant worsening of symptoms occurs, the individual notified or Principal Investigator will follow-up with the participant and will provide intervention as necessary. Reporting of Adverse Events and Serious Adverse Events will follow institutional procedures as laid out in SOPs and Research Ethics Board (REB) guidance.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eParticipants may find some questions in the questionnaires uncomfortable. Participants may refuse to answer any questions to which they do not want to respond. Expected adverse events include worsening fatigue, decline in symptoms reported at baseline related to the study intervention, and eye strain/fatigue from using the smartphone application.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFrequency and plans for auditing trial conduct {23}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAn internal study monitor will be selected prior to the start of the trial. The monitor will not be involved in data collection activities and will be one step removed from the clinical trial. \u0026nbsp;Before the launch of recruitment, the internal monitor will ensure that appropriate training has been completed and documented for all delegated study staff.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter enrollment of the first participant, the internal study monitor will review all documentation for this participant to ensure any errors or challenges are identified and resolved before being carried through subsequent participants. Throughout the duration of the study, the internal monitor will perform monitoring visits on a minimum quarterly basis, or more frequently as needed based on recruitment rates. An internal monitoring plan will guide the process and materials to be reviewed at each visit, as well as follow-up procedures. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt the end of study, the monitor will lead the study close out activities in collaboration with the study staff to ensure that all study records and essential documentation are complete and ready for analysis, REB closure and archiving.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThroughout the study, the Ottawa Hospital Research Institute (OHRI) Clinical Facilitators may also audit the study. These audits may be planned or unplanned. If an audit is requested, the study team will assist the OHRI in completing their review of the study. If the internal monitor discovers significant or repeated issues in their monitoring visits, they may request the assistance of the OHRI Clinical Facilitators for their recommendations. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAny subsequent modifications to the study protocol, including changes to study objectives, study design, patient population, sample sizes, study procedures, or significant administrative changes will be agreed upon by the Investigators and submitted to the REB of record for review and approval prior to implementation. Participants will be informed in writing of any modifications or new information that may impact their willingness to participate in the study. If required, participants may also be asked to sign a Consent Update Form, as approved by the REB.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDissemination plans {31a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe plan to take a diverse approach to our knowledge mobilization and dissemination plan. We have engaged the Public Health Agency of Canada (PHAC) as Knowledge Users in our study. PHAC will work with the investigator team to identify relevant targets of knowledge exchange activities within the federal health portfolio, as well as with national and international stakeholders. Primary outcomes publications refer to any presentation or publication that presents data on the primary outcome measure as detailed in this protocol. The primary outcome publication will be submitted within 6 months of the completion of data collection. The primary outcomes publication will be open-access and any secondary publications will be made open-access whenever possible.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll study results will be released to study participants, the general medical community, the general public and other identified stakeholders. Other forms of dissemination include academic publications, conference presentations, stakeholder meetings and presentations to the general public. Lay knowledge products will be designed in collaboration with lived experience partners to ensure that dissemination is impactful and relevant to the community.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThere is currently little evidence about the optimal treatment of Long COVID patients or the use of digital health platforms in this population. There are currently no systematic reviews of treatment for Long COVID and much of the existing literature is considered low quality evidence. Important operational issues relate to the privacy and confidentiality of any information stored on the app, however the study team has ensured safeguards are in place to minimize this risk. Additionally, navigating virtual visits and fluctuating lockdowns poses variable challenges throughout the duration of the study. The protocol has been designed to be delivered hybrid or fully virtual, if required, to seamlessly accommodate any changes in access to in-person resources. The results of this trial could result in rapid, scalable, and personalized care for people with Long COVID which will decrease morbidity after an acute infection. Results from this study will also inform decision making in Long COVID and treatment guidelines at provincial and national levels.\u003c/p\u003e \u003cdiv id=\"Sec63\" class=\"Section2\"\u003e \u003ch2\u003eTrial status\u003c/h2\u003e \u003cp\u003eThis study received initial approval by the OHSN-REB in September 2021, with an amended protocol approved (protocol version date 23 Feb 2022). Recruitment was opened in May 2022. At the time of writing this manuscript, one participant had been enrolled. The estimated completion date for primary data collection is May 2023.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eACE-Q; Adverse Childhood Events Questionnaires; ASSIST; Alcohol, Smoking and Substance Interview Screening Test; AUDIT; Alcohol Use Disorders Identification Test; CIHR; Canadian Institutes of Health Research; COWAT; Controlled Oral Word Association Test; CRF; Case Report Form; DSMC; Data and Safety Monitoring Committee; ECM; Electronic Case Management; EDCS; Electronic Data Capture System; FNRS; Fatigue Numeric Rating Scale; FSS; Fatigue Severity Scale; GAD-7; Generalized Anxiety Disorder 7-item scale; HEIA; Health Equity Impact Assessment; HVLT-R; Hopkins Verbal Learning Test Revised; GCP; Good Clinical Practice; IEQ-SF; Injustice Experience Questionnaire \u0026ndash; Short Form; NICE; National Institute for Healthcare and Excellence; OHRI; Ottawa Hospital Research Institute; OHSN-REB; Ottawa Health Sciences Network Research Ethics Board; OMC; Ottawa Methods Centre; OWN; Ontario Workers Network; PCL-5; PTSD Checklist-5; PCR; polymerase chain reaction; PHAC; Public Health Agency of Canada; PHQ-9; Patient Health Questionnaire 9-item scale; PNRS; Pain Numeric Rating Scale; PSQI; Pittsburgh Sleep Quality Index; QALY; Quality Adjusted Life Years; RAT; Rapid Antigen Test; REB; Research Ethics Board; RHP; Registered Health Professional; O-TMT; Oral Trail Making Test; TOH; The Ottawa Hospital; WAIS-IV;\u0026nbsp;Weschler\u0026rsquo;s Adult Intelligence Scale \u0026nbsp;- 4\u003csup\u003eth\u003c/sup\u003e Edition; WEMWBS; Warwick Edinburgh Mental Wellbeing Scale; WHO; World Health Organization; WHODAS; WHO Disability Assessment Scale; WSIB; Workplace Safety and Insurance Board.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions {31b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSH is the Principal Investigator; he conceived the study, led the proposal and protocol development. JW is the co-Principal Investigator; he conceived the study, contributed to development of the proposal and protocol. NE is the Clinical Research Program Manager; she drafted the proposal and the protocol. KT is a co-Investigator and Health Economist; she designed the cost effectiveness analysis plan. DC is a co-Investigator and biostatistician; he developed the statistical analysis plan. All authors contributed to the proposal, refinement of the study protocol, and all authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding {4}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is funded by the Canadian Institutes of Health Research (CIHR). The funders have no role in the design or conduct of the study or the decision to publish results.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials {29}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Principal Investigator will retain ownership of the dataset through the 10 year archiving period. Once the primary outcomes manuscript is published, the anonymized data set will be shared on an open access platform, such as Open Science Framework or Zenodo. Prior to this, any data required to support the protocol can be supplied upon request to the Principal Investigator (SH).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate {24}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval for this study has been granted by the Ottawa Health Sciences Network Research Ethics Board (OHSN-REB) (Protocol ID: 20210533-01H). Written, informed consent to participate will be obtained from all participants.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication {32}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eModel consent form available from corresponding author on request.\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests {28}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMK has consulting or speaking fees, unrelated to this trial or intervention, from HLS, Janssen, Otsuka, Lundbeck in last 2 years. TM, unrelated to this trial or intervention, has been a consultant for CHDI, Sunovion, Valeo Pharma, Roche, Biogen, nQ Medical and has been involved in Speakers Bureaus for Abbvie and Valeo Pharma.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll other authors have no competing interests to declare.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003cstrong\u003e\u0026rsquo;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003einformation (optional)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGovernment of Ontario. All Ontario: Case numbers and spread [Internet]. 2021 [cited 2021 Jul 12]. Available from: https://covid-19.ontario.ca/data\u003c/li\u003e\n\u003cli\u003eMahmud R, Rahman M, Rassel M, Monayem F, Sayeed S, Islam M, et al. 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JAMA - J Am Med Assoc. 2020;324(6):603\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eNational Institute for Health and Care Excellence, Royal College of General Practitioners, Healthcare Improvement Scotland. COVID-19 rapid guideline : Managing the long-term effects of COVID-19 [Internet]. NICE Guidelines. 2020. Available from: https://www.nice.org.uk/guidance/ng188/resources/covid19-rapid-guideline-managing-the-longterm-effects-of-covid19-pdf-66142028400325\u003c/li\u003e\n\u003cli\u003eDavis H, Assaf G, McCorkell L, Wei H, Low R, Re\u0026rsquo;em Y, et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021;38:101019. \u003c/li\u003e\n\u003cli\u003eTaquet M, Geddes JR, Husain M, Luciano S, Harrison PJ. 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: A retrospective cohort study using electronic health records. The Lancet Psychiatry [Internet]. 2021 Apr 1 [cited 2021 Apr 12];S2215-0366(21):00084\u0026ndash;5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/33836148\u003c/li\u003e\n\u003cli\u003eTenforde MW, Kim SS, Lindsell CJ, Billig Rose E, Shapiro NI, Files DC, et al. Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health vare systems network \u0026mdash; United States, March\u0026ndash;June 2020. Morb Mortal Wkly Rep. 2020;69(30):993\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eAyoubkhani D, Khunti K, Nafilyan V, Maddox T, Humberstone B, Diamond I, et al. Post-covid syndrome in individuals admitted to hospital with covid-19: Retrospective cohort study. BMJ. 2021;372(n693). \u003c/li\u003e\n\u003cli\u003eLam MHB, Wing YK, Yu MWM, Leung CM, Ma RCW, Kong APS, et al. Mental morbidities and chronic fatigue in severe acute respiratory syndrome survivors long-term follow-up. 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J Med Internet Res. 2021;23(3):e24380. \u003c/li\u003e\n\u003cli\u003eHatcher S, Heisel M, Ayonrinde O, Campbell JK, Colman I, Corsi DJ, et al. The BEACON study: protocol for a cohort study as part of an evaluation of the effectiveness of smartphone-assisted problem-solving therapy in men who present with intentional self-harm to emergency departments in Ontario. Trials. 2020;21(1):925. \u003c/li\u003e\n\u003cli\u003eAlibhai SMH, Santa Mina D, Ritvo P, Sabiston C, Krahn M, Tomlinson G, et al. A phase II RCT and economic analysis of three exercise delivery methods in men with prostate cancer on androgen deprivation therapy. BMC Cancer. 2015;15(1):312. \u003c/li\u003e\n\u003cli\u003eRitvo P, Obadia M, Santa Mina D, Alibhai S, Sabiston C, Oh P, et al. Smartphone-enabled health coaching intervention (iMOVE) to promote long-term maintenance of physical activity in breast cancer survivors: Protocol for a feasibility pilot randomized controlled trial. 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A brief measure for assessing generalized anxiety disorder. Arch Intern Med. 2006;166(10):1092\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eBuysse Charles F Reynolds Ill DJ, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research [Internet]. Vol. 28, Psychiatry Research. Available from: https://journals-scholarsportal-info.proxy.bib.uottawa.ca/pdf/01651781/v28i0002/193_tpsqiaifppar.xml\u003c/li\u003e\n\u003cli\u003eBlevins CA, Weathers FW, Davis MT, Witte TK, Domino JL. The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): Development and initial psychometric evaluation. J Trauma Stress. 2015 Dec;28(6):489\u0026ndash;98. \u003c/li\u003e\n\u003cli\u003eRabin R, de Charro F. EQ-5D: A measure of health status from. Ann Med. 2001;33:337\u0026ndash;43. \u003c/li\u003e\n\u003cli\u003eCarey KB, Carey MP, Chandra PS. 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Thorax. 1999;54(7):581\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eTennant R, Hiller L, Fishwick R, Platt S, Joseph S, Weich S, et al. The Warwick-Dinburgh mental well-being scale (WEMWBS): Development and UK validation. Health Qual Life Outcomes. 2007; \u003c/li\u003e\n\u003cli\u003eTrousselard M, Steiler D, Dutheil F, Claverie D, Canini F, Fenouillet F, et al. Validation of the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) in French psychiatric and general populations. Psychiatry Res. 2016;245:282\u0026ndash;90. \u003c/li\u003e\n\u003cli\u003eMaheswaran H, Weich S, Powell J, Stewart-Brown S. Evaluating the responsiveness of the Warwick Edinburgh Mental Well-Being Scale (WEMWBS): Group and individual level analysis. Health Qual Life Outcomes. 2012;10(156). \u003c/li\u003e\n\u003cli\u003eSullivan MJL, Adams H, Horan S, Maher D, Boland D, Gross R. The role of perceived injustice in the experience of chronic pain and disability: Scale development and validation. J Occup Rehabil. 2008;18(3):249\u0026ndash;61. \u003c/li\u003e\n\u003cli\u003eFelitti VJ, Anda RF, Nordenberg D, Williamson DF, Spitz AM, Edwards V, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: The adverse childhood experiences (ACE) study. Am J Prev Med. 1998; \u003c/li\u003e\n\u003cli\u003eXie F, Pullenayegum E, Gaebel K, Bansback N, Bryan S, Ohinmaa A, et al. A time trade-off-derived value set of the EQ-5D-5L for Canada. Med Care. 2016;54(1):98\u0026ndash;105. \u003c/li\u003e\n\u003cli\u003eManca A, Hawkins N, Sculpher MJ. Estimating mean QALYs in trial-based cost-effectiveness analysis: The importance of controlling for baseline utility. Health Econ. 2005;14(5):487\u0026ndash;96. \u003c/li\u003e\n\u003cli\u003eBai F, Tomasoni D, Falcinella C, Barbanotti D, Castoldi R, Mul\u0026egrave; G, Augello M, Mondatore D, Allegrini M, Cona A, Tesoro D, Tagliaferri G, Vigan\u0026ograve; O, Suardi E, Tincati C, BerBai F, Tomasoni D, Falcinella C, Barbanotti D, Castoldi R, Mul\u0026egrave; G, Augello M, Mondat MA, ingheli T, Varisco B, Battistini CL, Piscopo K, Vegni E, Tavelli A, Terzoni S, Marchetti G MA. Female gender is associated with long COVID syndrome: a prospective cohort study. Clin Microbiol Infect. 2021;S1198-743X. \u003c/li\u003e\n\u003cli\u003eIzcovich A, Ragusa MA, Tortosa F, Marzio MAL, Agnoletti C, Bengolea A, et al. Prognostic factors for severity and mortality in patients infected with COVID-19: A systematic review. PLoS One. 2020;15(11):e0241955. \u003c/li\u003e\n\u003cli\u003eRovere-Querini P, De Lorenzo R, Conte C, Brioni E, Lanzani C, Yacoub MR, et al. Post-COVID-19 follow-up clinic: Depicting chronicity of a new disease. Acta Biomed. 2020;91(9-S):22\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eSudre CH, Murray B, Varsavsky T, Graham MS, Penfold RS, Bowyer RC, et al. Attributes and predictors of long COVID. Nat Med. 2021;27:626\u0026ndash;31. \u003c/li\u003e\n\u003cli\u003eGovernment of Canada. Safeguarding your Research [Internet]. 2021. Available from: https://www.ic.gc.ca/eic/site/063.nsf/eng/h_97955.html\u003c/li\u003e\n\u003cli\u003eInternational Council for Harmonisation of Tecnical Requirements for Pharmaceuticals for Human Use. Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) [Internet]. 2016. Available from: https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf\u003c/li\u003e\n\u003cli\u003eMinistry of Health. Health Equity Impact Assessment Tool (HEIA) [Internet]. Governemnt of Ontario. 2008 [cited 2021 Jul 12]. Available from: https://www.health.gov.on.ca/en/pro/programs/heia/tool.aspx\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"COVID-19, SARS-CoV-2, Long-COVID, Post-COVID rehabilitation, Blended Care, Electronic Case Management","lastPublishedDoi":"10.21203/rs.3.rs-1723719/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1723719/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: As of May 2022, Ontario has seen more than 1.3 million cases of COVID-19. While the majority of individuals will recover from infection within four weeks, a significant subset experience persistent and often debilitating symptoms, known as “post-COVID syndrome” or “Long COVID”. Those with Long COVID experience a wide array of symptoms, with variable severity, including fatigue, cognitive impairment, and shortness of breath. Further, the prevalence and duration of Long COVID is unclear, nor is there evidence on the best course of rehabilitation for individuals to return to their desired level of function. Previous work with chronic conditions has suggested that the addition of electronic case management (ECM) may help to improve outcomes. These platforms provide enhanced connection with care providers, detailed symptom tracking and goal setting, and access to relevant resources. In this study, our primary aim is to determine if the addition of ECM with health coaching improves Long COVID outcomes at three months compared to health coaching alone.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: The trial is an open-label, single site, randomized controlled trial of ECM with health coaching (ECM+) compared to health coaching alone (HC). Both groups will continue to receive usual care. Participants will be randomized equally to receive health coaching (+/- ECM) for a period of 8 weeks and a 12-week follow-up. Our primary outcome is the WHO Disability Assessment Scale (WHODAS), 36-item self-report total score. Participants will also complete measures of cognition, fatigue, breathlessness, and mental health. Participants and care providers will be asked to complete a brief qualitative interview at the end of the study to evaluate acceptability and implementation of the intervention.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e: There is currently little evidence about the optimal treatment of Long COVID patients or the use of digital health platforms in this population. The results of this trial could result in rapid, scalable, and personalized care for people with Long COVID which will decrease morbidity after an acute infection. Results from this study will also inform decision making in Long COVID and treatment guidelines at provincial and national levels.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTrial registration\u003c/strong\u003e: ClinicalTrials.gov, NCT05019963, Registered on 25 August 2021, https://clinicaltrials.gov/ct2/show/NCT05019963\u003c/p\u003e","manuscriptTitle":"Enhancing COVID Rehabilitation with Technology (ECORT): Protocol for an open-label, single site randomized controlled trial evaluating the effectiveness of electronic case management for individuals with persistent COVID-19 symptoms.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-07-26 19:15:17","doi":"10.21203/rs.3.rs-1723719/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2022-07-19T13:15:26+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-07-19T13:04:25+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-06-16T04:54:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"Trials","date":"2022-06-03T14:50:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"49afc9a5-2e43-44db-99f2-e82ff8b602e4","owner":[],"postedDate":"July 26th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-07-26T19:15:17+00:00","versionOfRecord":[],"versionCreatedAt":"2022-07-26 19:15:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1723719","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1723719","identity":"rs-1723719","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}