By the end of 2023, more than 277 million confirmed SARS-CoV-2 infections were reported in Europe [1]. According to the World Health Organization (WHO), 10% to 20% of those who have been infected develop post–COVID-19 condition, also called long COVID. This condition is defined as “individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction, and generally have an impact on everyday functioning” [2]. Long-lasting symptoms affect not only hospitalized patients, but worryingly also nonhospitalized people after a mild infection [3].

Long COVID is a complex multisystem secondary condition [4] and a new disease of partly unknown pathogenesis [5-7]. Long-term symptoms following infection are similar to those found in conditions where the central nervous system is affected [5,6] and consist of key symptoms similar to chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) [8,9]. One of the main complaints reported by patients with long COVID is impaired cognitive function [9-13], which includes self-reported fatigue, memory deficits, difficulty concentrating, and difficulty in information processing. A variety of other persistent symptoms are reported, including headache, dyspnea, cough, chest pain, myalgia, joint pain, impaired mobility, sleep disorders, depression, and anxiety [10]. Symptoms of long COVID may lead to disability in everyday life, reduced health-related quality of life (HRQoL) [14,15], strain on the health care system, and substantial socioeconomic costs [15]. Moreover, long COVID is strongly associated with a reduction in workability [16].

Different treatment options are delivered to patients with long COVID: drug interventions, dietary interventions, or behavioral interventions [17]. In patients with complex illness, behavioral interventions are often an important factor stimulating recovery [18,19]. Behavioral interventions can vary in intensity (eg, number of consultations), content (eg, graded activity or aerobic training), modality (eg, group-based or individual), and may be mono- or multidisciplinary.

Cognitive behavioral therapy (CBT) is based on the theory that our body (symptoms), thoughts, feelings, and behaviors are interconnected. Adjustments in behavior and thoughts can be helpful for somatic symptoms, and adjustments can be implemented through home-based exercises [18]. Results of a randomized controlled trial (RCT) using CBT have shown significantly less severe fatigue in patients with long COVID across follow-up assessments compared to patients receiving standard care [20]. Participants received substantial follow-ups over 17 weeks, and the control group received care as usual. All secondary outcomes, including social and physical functioning, somatic symptoms, and concentration, also favored patients receiving CBT; however, HRQoL was not evaluated. Patients in this study were mostly nonhospitalized [20]. A recent review recommends behavioral interventions based on CBT as management of long COVID [17].

A previous systematic review reported that regular physical exercises increase physical performance, neurocognitive function as well as fatigue and HRQoL [3] in patients with long COVID. In a cohort study by Daynes et al [21], patients with long COVID showed improvements in all those parameters listed above after supervised exercise training (aerobic and strength training) in combination with education and pacing advice twice a week for 6 weeks. However, this study had only 30 participants and did not include a control group.

A case-control study by Palladini et al [22] detected improved cognitive performance in hospitalized patients with long COVID, with a correlation to measures of quality of life. The study intervention included cognitive exercises of the most affected cognitive domains and counseling follow-ups for 2 months. Furthermore, cognitive exercise in patients with long COVID is supported by several other studies [5,9,23].

According to the WHO, patients with long COVID may experience worsening of symptoms following minimal cognitive, physical, emotional, and social activity, or activity that could previously be tolerated [24]. A result of this is often a behavioral challenge where patients exceed their own tolerance limit, followed by complete rest, an all-or-nothing pattern. Others may generally fear activity because it may lead to exacerbation of symptoms, also called fear-avoidance. Such patterns are often seen in CFS/ME [25]. Graded fixed incremental exercise therapy is debated in the literature because it might cause PEM, which is associated with poor health outcomes [26-29]. Pacing, on the other hand, is how to balance activities and rest to avoid exacerbation of symptoms, and thus not fixed incremental steps [24]. In patients with long COVID, individualized activity plans with education on pacing should therefore be provided. It is documented as beneficial to gradually introduce activity to restore patients to previous levels of activity, including daily routines [5,30]. Interventions that combine pacing and graded escalation of physical and cognitive activities are called graded activity [25]. A recent review (2023) found graded activity based on elements from CBT to be effective in reducing fatigue and improving physical functioning in CFS/ME [25].

Findings from previous studies indicate that long COVID is a complex condition that can be treated by a graded activity intervention. Daily routines and regular physical and cognitive exercise may be 3 important focus areas in this behavioral management of long COVID.

Evidence from recent studies supports international guidelines [24,31] in terms of individual [17], multidisciplinary, and multimodal [15,21,32] rehabilitation approaches in long COVID.

In patients with CFS/ME, a self-management program delivered as group education without follow-up consultations did not have any effect compared to usual care on fatigue and physical functioning [33]. In contrast, a recent review on CFS/ME found that individual clinical follow-ups have an effect on fatigue and physical functioning [25]. Further, a digital individual self-efficacy program based on a holistic approach showed several benefits in supporting physical health and mental well-being in patients with long COVID [34].

Telerehabilitation, including video consultations, has also shown positive results in long COVID [35-37]. To ensure continuity in the rehabilitation process and promote self-management of individual rehabilitation goals [38], mobile apps have also shown effectiveness in long COVID [37,39,40].

Until today, rehabilitation studies in patients with long COVID are limited and show a substantial heterogeneity in treatment content, modality, and outcome measures, making it difficult to conclude the effectiveness [3,15,17]. Common to many interventions is that they provide clinical follow-ups over time, from 6 to 17 weeks [3,15,20,22,35]. It is still unclear how treatment content should be combined and which modality is most effective.

Recent comprehensive reviews propose conducting high-quality RCT studies to gain more insight into strategies for structuring the rehabilitation and examining the effectiveness of the management of long COVID [3,9,15,17,41]. It is unclear what treatment option is best to achieve the goal of restoring patients with long COVID to their previous levels of functioning [3], everyday function, including HRQoL [15], cognitive function [9], and workability [5-7]. More research is warranted to evaluate cognitive symptoms in patients with long COVID, and most conducted studies have used self-reported outcome measures [8,10]. Supplementing assessments with standardized neuropsychological tests may refine research findings.

To the best of our knowledge, no RCTs have so far investigated the management of long COVID with neurocognitive complaints comparing 2 rehabilitative interventions: a graded activity intervention with tailored individual follow-ups versus a one-day group course. Both intervention groups will be recommended to use the mobile app My COVID Rehabilitation as a supplement to the intervention for self-management of personal goals. Our RCT addresses the present knowledge gap, aiming to add robust evidence on what may be an effective rehabilitation approach for long COVID. The main research question is do tailored individual follow-ups give better outcomes in patients with long COVID compared to a 1-day group course? Additionally, the study will generate important knowledge about neuropsychological function and a digital self-management tool in long COVID rehabilitation.

This is a single-center, two-armed, parallel-group, superiority RCT with a 1:1 allocation ratio. Assessments are at baseline and at 3, 6, and 12 months. Participants will receive either individual rehabilitation (intervention group) or a 1-day group course (standard treatment). The study is embedded in ordinary clinical care at the University Hospital of North Norway (UNN). No blinding is performed except for a blinded statistical evaluation.

A total of 62 adult participants will be included in this trial at the outpatient regional long COVID clinic at UNN. Patients are first thoroughly examined by their general practitioners to exclude other underlying diseases explaining current symptoms. Patients with symptoms of long COVID are referred to our regional long COVID clinic where clinical assessment is done primarily in a video consultation. The assessment is done by a bi-disciplinary team led by a doctor, supplemented by either a physiotherapist or a psychologist based on the medical history. During the video consultation, patients are briefly informed about the study, and consent for a SMS text message invitation is obtained.

Individuals will be included if they had (1) symptoms attributable to long COVID affecting daily activities according to the WHO’s definition, (2) a positive COVID-19 test via a home test or polymerase chain reaction test, (3) neurocognitive symptoms, (4) age between 18 and 65 years, and (5) ability and willingness to provide informed consent. Exclusion criteria were as follows: (1) patients who did not want to comply with the planned physical study visits, (2) patients who were unable to complete surveys in Norwegian, and (3) patients with known chronic neurocognitive disease before COVID-19 or other diseases that can explain current symptoms. The inclusion age is set to 18 to 65 years, as one of the outcome measures in the study is return to work.

After assessment in the COVID clinic, eligible patients will receive an SMS text message invitation with a link to an information sheet and consent form (Multimedia Appendix 1). Patients are encouraged to contact the research coordinator by phone for supplementary information and possibly provide oral consent. Written informed consent is collected at the first visit. Each participant has the right to withdraw from the study at any time. Any adverse events will be recorded. The research coordinator is responsible for the enrollment process.

Participants will be block randomized with the computer program Research Electronic Data Capture (REDCap) either to the intervention group (n=31) or standard treatment group (n=31), presented in Figure 1.

Standard treatment at UNN is a one-day multidisciplinary group course. The duration is 6 hours, including breaks. Each group consists of 8 to 10 participants. The aim of the course is to improve self-management of long COVID. The course provides education about (1) sustaining factors of long COVID based on elements from a CBT framework, (2) activity regulation, (3) the importance of daily routines, and the advantages of both (4) physical and (5) cognitive exercise. Information is provided by a doctor, a psychologist, and an occupational therapist or a physiotherapist. Exchange of experience between participants is also facilitated. No follow-up consultations are provided. Information about the mobile app supplement is offered; a mobile app called My COVID Rehabilitation. The participants can voluntarily download the mobile app as a supplement, and personal goals can be noted and adjusted.

The intervention in this study is delivered individually by a physiotherapist following the study instructions described in Textbox 1. The physiotherapist may consult the multidisciplinary team if necessary. The intervention begins with a physical consultation where symptoms, function in everyday life, sustaining factors, and resources are thoroughly assessed. Education about long COVID based on elements from a CBT framework [18] is provided. Tailored to the participant’s life, a personalized rehabilitation plan is created, consisting of home-based exercises to facilitate a combination of pacing and graded escalation of physical and cognitive activities. The home-based exercises have 3 focus areas: daily routine, physical activity, and cognitive training. The plan consists of weekly personal goals to guide the participant’s progress. Three video-follow-up consultations are given to support change and to encourage participants to adjust personal goals in step with recovery within the 3 focus areas. Supported by the physiotherapist, the personalized goal setting is then verbalized and adjusted during the follow-up consultations. In total, 4 consultations are given within 6‐8 weeks. Voluntarily, the participants can download the My COVID Rehabilitation mobile app as a supplement, where the goals can be noted and adjusted.

Questionnaires will be sent to participants by email and captured by REDCap. The questionnaires are web-based and answered online. Reminders will be sent, if needed, by email once, SMS text messaging twice, and phone call once to improve adherence. If the participants have any questions regarding the questionnaires, they will be offered help by the research coordinator. The questionnaires will capture patient-reported outcome measurements at baseline and at 3, 6, and 12 months, including EQ-5D-5L index, EQ-5D-5L VAS, Chalder Fatigue Scale, number of symptoms, work participation, and feasibility of mobile app. At baseline, the patient also reports demographic data and relevant background information. Data is stored securely, and only the research team has access to the data. An overview of the measures and timepoints for assessments is presented in Table 1.

The primary outcome is HRQoL at the 6-month follow-up, assessed using the well-known EQ-5D-5L that gives a total index score [43,52]. EQ-5D-5L is a validated generic scale [52] and has also been applied and shown to be responsive to long COVID [37,53,54]. The 5 dimensions include mobility, self-care, usual activity, pain and discomfort, and anxiety and depression. Each dimension is assessed with 1 question, which has 5 levels of severity (“no,” “slight,” “moderate,” “severe,” and “extreme” problems). The Norwegian score has a range from −0.453 to 1, where 0 equals death and 1 is perfect health [55].

A comprehensive neuropsychological assessment will be conducted at baseline and repeated at 6 months to evaluate 4 key cognitive domains. The following measures from standardized tests will be used to measure aspects of the 4 selected cognitive domains.

Raw test scores are standardized using age-corrected published population norms. When available, published normative data from Scandinavian populations are prioritized. Scores will be reversed where necessary (reaction time) to ensure that higher scores consistently indicate better performance. Each assessment session will last 90 minutes, and the tests will be administered by a psychologist or trained health care personnel under supervision.

As part of this study, and at the request of our user representative, a mobile app was developed. The app has been named My COVID Rehabilitation (Norwegian: Min COVID Rehabilitering). Both groups will be invited to download the mobile app. The mobile app is a digital pamphlet with relevant information, including the possibility to make personal notes and goals based on activities from the 3 focus areas. Users will receive a daily reminder of their goals. After completing the activity, a simple digital reward is provided. The mobile app is available on the App Store and Google Play, and only the participant will have access to personal notes and goals in the mobile app on their phone. The mobile app has been developed in collaboration with user representatives, the multidisciplinary health care team at UNN, and system developers at Information and Communication Technology, Northern Norway Regional Health Authority. In the development process, feedback was given at several time points and adjustments made on both content, phrasing, and visual presentation.

This trial is embedded in ordinary clinical care at UNN with the last author (M Wilhelmsen) as project leader. At the same time, the study is part of a national research collaboration called ReCover. Participants are therefore invited to participate in voluntary supplement investigations at baseline and at 6-month follow-up. Written informed consent, including the collection, storage, and use of participant data, is obtained at the first visit. Explorative investigations of immunological, inflammatory, and metabolic changes of markers in plasma/serum and whole blood RNA and EEG/MRI are done to explore changes in brain volume, density of white matter fiber tracts, and brain activity. The ReCover study will explore if immune profile and changes in the brain are modulated by the intervention. Details on these supplementary investigations will be provided in other articles from the ReCover research group.

The Regional Committee for Medical and Health Research Ethics in northern Norway (number 587293) approved this study based on protocol version 5, April 12, 2024.

The study has been registered at ClinicalTrials.gov under the identifier NCT06085911. This study will be conducted according to the ethical principles of the Declaration of Helsinki (2013) [65]. Written informed consent will be obtained from all included participants before baseline assessments. Consent and personal data are stored using a linkage key with deidentified data on a secure, closed research server. All personal data will be deidentified during analysis and dissemination of results. Participants do not receive any compensation for participating in the project, and they can unconditionally withdraw at any time.