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Abstract

Long COVID symptoms include cognitive and physical deficits impacting one’s functional performance and quality of life. Limited evidence examines the use of cognitive interventions provided by occupational therapists in treating long COVID symptoms among adults. This systematic review summarizes existing studies on cognitive interventions and rehabilitation to treat long COVID symptoms and discusses their potential use within the scope of occupational therapy practice. We identified literature from 2021 to 2023 through searches of MEDLINE, CINAHL, PsycINFO, Cochrane Trials, and Scopus databases. Nineteen articles met inclusion criteria and were categorized into five types of intervention: (a) cognitive training, (b) cognitive behavioral therapy, (c) neurostimulation, (d) neurostimulation combined with cognitive training, and (e) multi-component rehabilitation programs. Strong evidence supports cognitive training, moderate supports cognitive behavioral training and low-level evidence supports other interventions provided by occupational therapists to target long COVID cognitive symptoms in adults.

Plain Language Summary

Long COVID Occupational Therapy Options: Systematic Review

Long COVID is defined as COVID symptoms continuing for 1 to 3 months or more, which affects the mental, cognitive, and physical systems, impacting the quality of life and ability to participate in meaningful activities. Few research studies have examined the effectiveness of treatments used by occupational therapists for adult clients with long COVID symptoms involving cognitive problems. This review summarizes research studies on these treatments and discusses their potential use in occupational therapy practice. Of the 338 potential research articles identified; 19 met the search criteria and five types of occupational therapy cognitive interventions to address long COVID symptoms in adults were found. Research about the interventions ranged from low-level to strong evidence.

Keywords

cognitive impairment cognitive rehabilitation systematic review treatment effectiveness

Beginning in 2019, COVID-19 infected more than 770 million people globally (World Health Organization [WHO], n.d.) and continues to infect people worldwide (WHO, n.d.). Many people continue to experience symptoms after their acute COVID-19 infections subside. This condition is referred to in the literature as post-acute sequelae of COVID, long-haul COVID, and long COVID (Centers for Disease Control and Prevention [CDC], 2023). Studies show that 10% to 20% of people with COVID go on to develop long COVID (Vahratian et al., 2024).

Long COVID is defined as an infection-associated chronic condition that occurs after SARSCoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems (National Academies of Sciences, Engineering, and Medicine [NASEM], 2024). Being a new diagnosis, the required duration for diagnostic purposes varies between health care professionals and researchers. For this review, we will operationally define it as COVID-19 symptoms persisting for at least 1 month. Symptoms of long COVID may include fatigue, “brain fog,” shortness of breath, pain, cognitive deficits, dizziness, sleep dysfunction, depression, and anxiety (CDC, 2023). These symptoms can negatively affect a person’s ability to participate in desired activities, impacting the integration of thinking and processing skills to complete everyday activities in various settings (American Occupational Therapy Association [AOTA], 2021). Cognitive rehabilitation has been used to address other cognitive conditions and may be effective for treating long COVID symptoms, which will be explored in this review (Giles et al., 2019).

Cognitive rehabilitation refers to interventions that aim to achieve changes in functional performance through remedial and compensatory approaches (Chester & Ruff, 2014). Since cognitive rehabilitation is tailored for each person, these diverse interventions have provided evidence for addressing a variety of conditions, such as traumatic brain injuries (TBI) and cerebral vascular accidents (CVAs; Giles et al., 2019). The use of cognitive rehabilitation for long COVID is emerging as a group of evidence-based treatments to address these functional impairments.

Certain cognitive interventions aim to reduce the impact of deficits in memory, learning, perception, language, thinking, and reasoning have been used to increase blood flow to the brain (Beaumont, 2004). Because some long COVID symptoms may result from insufficient blood flow to the brain, these interventions may be viable options to reduce those symptoms (Sabel et al., 2021).

A previous systematic review found evidence supporting cognitive interventions and rehabilitation approaches as more beneficial than conventional rehabilitation when addressing neurocognitive impairment and functional limitations following conditions, such as TBI and CVA (Cicerone et al., 2011). Understanding their effect on long COVID and its unique symptomology is essential for the rehabilitation field and those affected by long COVID.

The multi-system symptoms of long COVID contribute to decreased quality of life, impaired capacity to work, reduced endurance, and significant disability among adults (O’Mahony et al., 2022). These changes in function can contribute to decreased independence in everyday activities and reduced quality of life and life expectancy, so prioritizing resources for mitigating the burden of these functional disabilities may increase quality of life and life expectancy (McGrath et al., 2019). Following a debilitating loss of function, occupational therapy practitioners can facilitate regaining the activities, roles, and routines that are meaningful to individuals with long-term symptoms of COVID. Occupational therapists use holistic approaches to develop cognitive rehabilitation strategies that address these long COVID symptoms. This review aims to provide health care professionals with an examination of current evidence supporting approaches to improve functional performance in basic activities of daily living, instrumental activities of daily living, functional cognition, social participation, leisure, and rest and sleep for adults with long COVID. This information aims to equip health care professionals with effective client-centered care throughout rehabilitation. The purpose of this systematic review is to examine the current evidence surrounding cognitive rehabilitation interventions and approaches to support persons with long COVID.

Method

Protocol

This systematic review used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Page et al., 2021). In 2023, this study was registered in the International Prospective Register of Systematic Reviews (PROSPERO Registration No. CRD42023452504).

Search Strategy

MeSH and broad key terms were used to conduct a systematic literature search across five databases on July 25, 2023: MEDLINE (Ovid), CINAHL, PsycINFO (Ovid), Cochrane Trials, and Scopus. The complete search strategy for Scopus used Boolean combinations of the following key terms included: Index terms (“Post-Acute COVID-19 Syndrome”) OR title/abstract/key terms ((“post-acute” OR post OR long OR persistent* OR post-acute OR long-haul OR sequelae OR survivor) within three words of (covid* OR sars-cov-2)) AND index terms (“Occupational Therapy”) OR title/abstract/keyterms (ergotherap* OR “occupational therap*”) OR index terms (“Cognitive Behavioral Therapy”) OR index terms (“Cognitive Training”) OR title/abstract/key terms ((cognitive OR cognition) within three words of (intervention* OR program* OR therap* OR rehab* OR train* OR psychotherap*)). A similar search string was used for the other databases, depending on their specific subject headings. The search strategy was devised with the assistance of a reference librarian at the University of Texas Medical Branch Moody Medical Library. Hand searches were conducted through MEDLINE (PubMed), MEDLINE (Ovid), and article reference lists to prevent the omission of relevant studies.

Selection Criteria

Selected records were screened with Covidence software using predetermined selection criteria by the review team. Selection criteria considered study participants, interventions and rehabilitation strategies, and targeted outcomes. Participants were 18+ years old and had been diagnosed with long COVID. Symptoms included fatigue, “brain fog,” shortness of breath, pain, cognitive deficits, dizziness, sleep dysfunction, depression, and anxiety. Long COVID diagnoses were determined from self-report assessments or clinical assessments. Interventions or program participation included cognitive interventions aimed to reduce the impact of deficits in memory, learning, perception, language, thinking, and reasoning. Cognitive rehabilitation strategies were systematic, functionally oriented services of therapeutic activities based on assessment and understanding of brain-behavioral deficits. These strategies also addressed non-cognitive symptoms, such as fatigue and sleep difficulties, which can benefit from using cognitive interventions and rehabilitation strategies. All outcomes targeting symptoms of long COVID were included. Due to limited articles that met inclusion criteria, all intervention studies, including case studies, were included to examine existing research on treating long COVID. The exclusion criteria were: (a) people currently infected with COVID-19, (b) people not experiencing continuing or new symptoms, (c) children, and (d) study designs consisting of protocols, systematic reviews, meta-analyses, and expert opinions.

Data Collection

Data collection was independently completed by the first five authors using Covidence software to manage and screen articles that met inclusion criteria. Those meeting the inclusion criteria received a full-text appraisal. Two votes were required to include or exclude an article. If discrepancies in votes occurred, a third author would perform an additional screening to finalize the decision.

Quality Assessment

The articles meeting all inclusion criteria were evaluated for scientific rigor and risk of bias. The selected studies were assessed and assigned appropriate levels of evidence as created by the Oxford Center for Evidence-Based Medicine (OCEBM Levels of Evidence Working Group, 2009). The risk of bias in the studies was assessed using AMSTAR, A Measurement Tool to Assess Systematic Reviews (Shea et al., 2017), and the Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group (National Heart Lung and Blood Institute, 2014). The strength of evidence was assessed using guidelines from the U.S. Preventive Services Task Force (2012).

Results

Final Studies

After the initial search, 338 articles were retrieved and screened according to the inclusion criteria, with 268 excluded. A full-text review was completed on 70 articles, and 19 were included in the final review. The PRISMA flowchart diagram depicting the review process is presented in Figure 1. Risk of bias results obtained using the AMSTAR and Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group reflect a moderate risk of bias in 18 of the 19 studies and a high risk of bias in one study because blinding of the participants and outcome measures were unachievable. See Tables 1 and 2 for details.

Figure 1.

Search Flow Diagram.

Table 1.

Risk of Bias for Randomized and Non-Randomized Control Trials.

Citation	Selection bias (risk of bias arising from randomization process)			Performance bias (effect of assignment to intervention)		Detection bias		Attrition bias	Reporting bias	Overall risk of bias assessment (low, moderate, high risk)
Citation	Random sequence generation	Allocation concealment (until participants enrolled and signed)	Baseline differences between intervention groups (suggest problem with randomization)	Blinding of participants during the trial	Blinding of study personnel during the trial	Blinding of outcome assessment: self-reported outcomes	Blinding of outcome assessment: Objective outcomes (assessors aware of intervention received?)	Incomplete outcome data (data for all or nearly all participants?)	Selective reporting (results being reported selected on the basis of the results?)	Overall risk of bias assessment (low, moderate, high risk)
Duñabeiti et al. (2023)	–	−	+	–	–	–	–	+	+	Moderate risk
Garcia-Molina et al. (2022)	–	–	–	–	–	–	?	+	+	High risk
Hausswirth et al. (2023)	+	+	+	–	–	?	?	+	+	Moderate risk
Kuut et al. (2023)	+	+	+	–	–	–	–	+	+	Moderate risk
Palladini et al. (2023)	–	–	+	–	–	–	–	+	+	Moderate risk
Toussaint and Bratty (2023)	+	+	?	+	?	–	–	+	+	Moderate risk

Source. Table format adapted from Shea et al. (2017).

Note. Key = Yes (+), No (–), Not sure (?). Scoring for overall risk-of-assessment is as follows: 0–3 minuses, low risk of bias (L); 4–6 minuses, moderate risk of bias (M); 7–9 minuses, high risk of bias (H).

Table 2.

Risk of Bias for Before-After (Pre-Post) Studies With No Control Group.

Citation	Study question or objective clear	Eligibility or selection criteria clearly described	Participants representative of real world patients	All eligible participants enrolled	Sample size appropriate for confidence- in findings	Intervention clearly described and delivered consistently	Outcome measures pre-specified, defined, valid/reliable, and assessed consistently	Assessors blinded to participant exposure to intervention	Loss to follow-up after baseline 20% or less	Statistical methods examine changes in outcome measures from before to after intervention	Outcome measures were collected multiple times before or after intervention	Overall risk of bias assessment (low, moderate, high risk)
Andrade (2023)	Y	Y	Y	NR	N	Y	Y	N	N	N	Y	Moderate
Bogucki & Sawchuk (2023)	Y	Y	Y	NR	N	Y	Y	N	NR	N	N	Moderate
Cavendish et al. (2022)	Y	Y	Y	NR	N	Y	NR	N	N	N	N	Moderate
Harenwall et al. (2021)	Y	Y	Y	NR	N	Y	Y	N	Y	Y	N	Moderate
Hasting et al. (2023)	Y	Y	N	NR	N	Y	Y	N	Y	Y	N	Moderate
Łuckoś et al. (2021)	Y	Y	Y	NR	N	Y	Y	N	Y	N	N	Moderate
Polevaya et al. (2022)	Y	Y	N	NR	N	Y	N	N	Y	Y	N	Moderate
Rabaiotti et al. (2023)	Y	Y	N	NR	N	Y	Y	N	NR	Y	N	Moderate
Raunkiaer et al. (2023)	Y	Y	N	NR	N	Y	Y	N	Y	N	N	Moderate
Sabel et al. (2021)	Y	N	N	NR	N	Y	Y	N	NR	Y	Y	Moderate
Skilbeck (2022)	Y	N	N	NR	N	Y	N	N	N	Y	N	Moderate
Wilcox & Frank (2021)	Y	N	N	NR	N	Y	Y	N	Y	Y	N	Moderate
Zhang & Zhang (2023)	Y	N	N	NR	N	Y	N	N	Y	Y	N	Moderate

Source. Table format adapted from National Heart Lung and Blood Institute (2014).

Note. Key = Yes (Y), No (N), Not reported (NR). Scoring for overall risk of bias assessment is as follows: 0–3 N, Low risk of bias (L); 4–8 N, Moderate risk of bias (M); 9–11 N, High risk of bias (H).

The 19 selected studies were conducted across various settings and included adults at least the age of 18 years. Settings consisted of hospitals, inpatient settings, outpatient clinics, and virtual at-home treatment; however, multiple studies did not disclose the specific study settings. Studies were conducted in the United States, United Kingdom, Italy, Russia, Spain, Germany, Brazil, Netherlands, Poland, and Denmark. Further characteristics of the included studies are summarized in Table 3.

Table 3.

Evidence Table for the Studies Included in the Systematic Review.

Author/year/country	Level of evidenceStudy designRisk of bias	ParticipantsInclusion criteriaStudy setting	Intervention and control groups	Outcome measures	Results
Andrade (2023) United States	Level 4 Case report Risk of bias Moderate	Participants N = 1 (male, age 63) Inclusion criteria Primary diagnosis of long-COVID with impacts on daily life and lifestyle health behaviors. Intervention setting Inpatient rehabilitation unit (IRU) in large hospital system	Intervention group Nine 90-min occupational therapy sessions using goal-directed interventions focusing on reflexive thinking, self-awareness, and cognitive strategies to increase participation in ADLs and IADLs and ease habit creation and tracking. Control Group None	Functional performance • Activity Measure for Post-Acute Care (AM-PAC)	Significant findings In this context, the occupational therapy process was shown to produce measurable results and positive outcomes for improving long-COVID’s impact on engagement in life skills within the inpatient rehabilitation setting. Non-significant Findings None
Bogucki & Sawchuk (2023) United States	Level 4 Case report Risk of bias Moderate	Participants N = 1 (female, age within 30s) Inclusion Criteria Individual with PTSD who had multiple COVID-19 infections and was diagnosed post-COVID syndrome. Intervention Setting Primary Care Psychiatry	Intervention group 12-sessions of cognitive processing therapy (CPT) for PTSD once a week, including in-session content and between-session assignments. Control Group None	Psychological • PTSD Checklist—Civilian Version (PCL-C) • Patient Health Questionnaire-9 (PHQ-9) • Generalized Anxiety Disorder Scale-7 (GAD-7)	Significant Findings Following a CPT demonstrated a clinically significant reduction of PTSD symptoms (32 point decrease, 60%). In addition, at the end of intervention, the participant did not report enough symptoms or functional limitations to satisfy the diagnostic criteria for PTSD or any other psychiatric disorder outlined in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association, 2013). Non-significant Findings None
Cavendish et al. (2022) Brazil	Level 4 Case Series Risk of Bias Moderate	Participants N = 4 (M age, 50.5 years; 75% female) Inclusion Criteria Individuals with long COVID cognitive symptoms clinically evaluated using the Assessment of post-acute sequelae of Sars-Cov2 (A-PASC) inventory. Intervention Setting Unidentified setting in association with the Universidade de São Paulo	Intervention Group Interventions consisted of 20 daily 20-min sessions of bilateral prefrontal transcranial direct current stimulation (tDCS) followed by online cognitive training using the BrainHQ platform. Control Group None	Physical, cognitive, and emotional symptoms and Functional abilities • A-PASC inventory Mood and anxiety scales • Quick Inventory of Depression Symptomology (QIDS) • Positive and Negative Affect Schedule (PANAS) • State-Trait Anxiety Inventory (STAI) Cognitive screening • Montreal Cognitive Assessment (MoCA) Premordib intelligence • Word Accentuation Test—Brazilian Version (WAT-Br) Verbal episodic memory • Rey Auditory Verbal Learning Test (RAVLT) Visual memory • Rey-Osterrieth Complex Figure—Recall Attention • Test of Divided Attention (TEADI) • Test of Sustained Attention (TEACO) Language • Brazilian version of the Bachy Languedock oral naming test (TENON) • Semantic verbal fluency • Phonemic Verbal Fluency (FAS) Executive functioning • Barkley Deficits in Executive Functioning Scale (BDEFS) • Five-Digit Test (FDT)	Significant Findings Participants had significant improvements in symptoms of depression, processing speed, delayed and immediate recall, self-reported cognitive symptoms, emotional symptoms, functional abilities, and executive functioning. Non-significant Findings None
Duñabeitia et al. (2023) Spain	Level 3B Before-and-After Feasibility Study with pre-post design Risk of Bias Moderate	Participants N = 73 (M age, 46.1 years; 90% female) Inclusion Criteria Adults (18+), reported being affected with COVID-19 at least 3 months prior to expression of interest, and experience cognitive symptoms related to Post-acute sequelae of COVID-19 (PASC). Intervention Setting Intervention was received virtually at the participants’ home	Intervention Group 73 participants completed as many cognitive daily training sessions as they desired within an 8-week period using a personalized computerized cognitive training (CCT) intervention at home. Control Group None	Cognition • Cognitive Assessment Battery (CAB) PRO	Significant Findings Participants received higher cognitive scores within all domains (perception, attention, memory, coordination, and reasoning) following the 8 week CCT period. Cognitive improvement increased as a function of the amount of training completed for all domains. Non-Significant Findings Test moment and domain interactions and age were not statistically significant.
Garcia-Molina et al. (2022) Spain	Level 3B Nonrandomized pre-posttest study Risk of Bias High	Participants N = 123 (M age, 51.02 years; 58.5% female) Inclusion Criteria 18+ at the time of the infection, PCR-confirmed SARS-CoV-2 infection, meets criteria for post-COVID-19 syndrome according to the British National Institute for Health and Care Excellence (NICE). Intervention Setting Outpatient Rehabilitation Program via Telehealth	Intervention Group 91 participants showed cognitive alterations and underwent treatment for cognitive symptoms as part of the post–COVID-19 syndrome outpatient rehabilitation program. Control Group 32 participants presented normal results in the neuropsychological examination and therefore did not receive treatment for cognitive symptoms.	Cognitive • Barcelona Test—orientation to person, space, and time subtests • Wechsler Adult Intelligence Scale III (WAIS III) • Rey Auditory Verbal Learning Test (RAVLT) • Verbal Fluency Test Psychological • Hospital Anxiety and Depression Scale (HADS) • Brief semi-structured follow-up interview	Significant Findings Both the intervention and control group showed improvement in cognitive performance in pre- and post-treatment scored. The intervention group had a larger effect size in the backward digit span, RAVLT, verbal fluency, and HADS. However, follow-up interview results indicated participants could not return to their prior level of functioning pre-COVID-19 infection. Non-Significant Findings None
Harenwall et al. (2021)	Level 4 Case Series Risk of bias Moderate	Participants N = 149 (M age, 47.25 years; 81% female) Inclusion Criteria Individuals suffering from post-COVID-19 syndrome Intervention setting Telehealth (Microsoft teams)	Intervention Group 149 participants received a 7-week course called “Recovering from COVID” where they received strategies for sleep hygiene, nutrition, activity management, energy conservation, stress management, and breathing techniques. Control Group: None	Health-Related Quality of Life • Visual Analog Scale (VAS) • EuroQol EQ-5D-5L (mobility, self-care, usual activities, pain/discomfort, anxiety or depression)	Significant Findings Significant improvements in quality-of-life outcomes. In post-course assessments, 53.9% reported an improved health state, 7.9% reported no change, 10.5% reported a worse health state, and 22.4% reported a mixed change in health state. Non-significant findings No statistically significant effects between participants who completed the follow up and those that did not.
Hasting et al. (2023) Germany	Level 3B Nonrandomized pre-posttest study Risk of Bias Moderate	Participants N = 33 (M age, 49.2 years; 72.7% female) Inclusion Criteria Referred to the interdisciplinary post-COVID outpatient consultation from a general practitioner or specialist, seeking treatment and had sufficient resilience for a day-clinic setting, between 18 and 65 years with mild to moderate cognitive impairment and/or fatigue complaints Intervention Setting Leipzig University Hospital	Intervention Group 33 participants received 10 treatment days within 3-weeks composed of neurorehabilitation and cognitive behavioral therapy (CBT) components. Days without treatment were used for home assignments, including weekends. Control Group None	Attention • Trail Making Test (TMT) • Test of Attentional Processing (TAP) Memory• Wechsler Memory Scale Revised (WMS-R) • California Verbal Learning Test (CVLT) Executive Functions • Test of Logical Reasoning (LPS-3) • Standardized Link’sche Probe test of action planning and control (SLP) • Test of verbal fluency (RWT) • STROOP-Test paradigm (FWIT) Psychological • Beck Depression Inventory (BDI-II) General Health • Symptom Checklist-90 (SCL-90) • HEALTH-49 Scale Fatigue • Fatigue Symptom Severity (FSS) • Fatigue Impact Scale (FIS) Sleep Disorders • Epworth Sleepiness Scale (ESS)	Significant Findings Patients reported general improvements in well-being and had a significant increase in self-efficacy, activities and participation, mental health measures, and general psychological distress. Non-Significant Findings No significant difference in self-reported fatigue.
Hausswirth et al. (2023)	Level 1B Randomized Control Trial Risk of Bias Moderate	Participants N = 49 (M age, 47.23 years; 71.4% female) Inclusion Criteria All participants were 18 years or older, the absence of dementia or neuropsychiatric disorders, as a diagnosis of long COVID confirmed by SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) or serology and scores in screening questionnaires ≥ 8 for the HADS-A/HADS-D subscales, ≥ 4 for the Chalder Fatigue Scale and ≤ 17 for the SSQ. Inclusion for the healthy normative group were participants 18 years or older, the absence of dementia or neuropsychiatric disorders and absence of SARS-CoV-2 confirmed by a serological test and the same screening questionnaires mentioned above. Intervention Setting Not disclosed	Intervention Group 17 participants with long COVID were randomized to the intervention group (G-Int; n = 17). G-Int participated in 10 30-min sessions of the Rebalance program over a period of 5 weeks. Each session included sound therapy and coach-guided meditation associated with light stimulations. Control Group 17 participants with long COVID were randomized to the control group (G-Con; n = 17). There was an extra group for healthy participants, which was the normative group (G-Nor; n = 15).	Fatigue • Chadler Fatigue Scale Psychological • Perceived Stress Scale • Profiles of Mood States • Hospital Anxiety and Depression Scale Sleep Quality • Speigel Questionnaire Pain • Visual Analog Scale (VAS) Cognition • Computerized choice response time task • Computerized pattern comparison task • Simon Task • Pursuit Rotor Task • Computerized Corsi block-tapping task	Significant Findings Compared to the healthy subjects, long COVID patients showed significant differences at baseline on all report questionnaires. At program conclusion, G-Int had a significant improvement in cognitive function, particularly in the reduction in reaction times. G-Int showed significant decreases in physical and mental fatigue, muscle and joint pain, psychological disturbances, and had significantly improved sleep quality. Non-Significant Findings None
Kuut et al. (2023) Netherlands	Level 1B Randomized Control Trial Risk of Bias Moderate	Participants N = 114 (M age, 45.85 years; 72% female) Inclusion Criteria All participants were 18 years or older and had a previous diagnosis of COVID-19. They were required to have experienced severe fatigue within 3 to 12 months following their COVID-19 diagnosis, as indicated by a CIS fatigue score of 35 or higher. In addition, their scores on the physical functioning subscale of the SF-36 had to be 65 or lower, and/or they needed a social functioning score of 10 or higher on the WSAS. Proficiency in the Dutch language was also a prerequisite for participation. Intervention Setting: Multicenter. Included Hospital Outpatient Clinics	Intervention group 57 participants received Cognitive Behavioral Therapy (CBT) for 17 weeks. Control group 57 participants received care as usual (CAU) for 17 weeks.	Fatigue • Checklist Individual Strength (CIS-fatigue) Physical Functioning • Physical functioning subscale of the Short Form Health Survey (SF-36) Social Functioning • Work and Social Adjustment Scale (WSAS) Somatic Symptoms • Patient Health Questionnaire (PHQ-15) Concentration • Subscale of Checklist Individual Strength (CIS-conc)	Significant Finding The participants who received the CBT were significantly less fatigued as compared with the CAU control group. There was a significant difference between the CBT and CAU groups across all secondary outcome measures, with each outcome favoring the CBT group. Non-Significant Findings None
Łuckoś et al. (2021) Poland	Level 4 Case report Risk of Bias Moderate	Participants N = 1 (female, age 48) Inclusion Criteria Continued symptoms post SARS-CoV-2 infection Currently experiencing neuroCOVID-19 Intervention Setting Reintegration and Training Center of the Polish Neuropsychological Society	Intervention Group One participant received neurotherapy, a combination of EEG-neurofeedback and goal-oriented cognitive training, 2× a week for 15 weeks. Additional sleep, exercise, diet, and social connection strategies were implemented. Control Group None	Intelligence/IQ • Wechsler Adult Intelligence Scale- Revised (WAIS-R) Memory • Wechsler Memory Scale (WMS-II) Executive Function • TrialMaking Test (TMT) Neuropsychological Function • Authorized Polish Version of the Boston Naming Test • The Stroop Color and Word Test (SCWT) • Wisconsin Card Sorting Test (WCST) Understanding • Polish Version of the Token Test	Significant Findings The participant’s verbal and non-verbal IQ increased significantly after the neurotherapy program. There was improvement seen in almost all cognitive functions assessed. Non-Significant Findings None
Palladini et al. (2023) Italy	Level 4 Case-control Study Risk of Bias Moderate	Participants N = 45 (M age, 58.2 years; 65% male) Inclusion Criteria Admission to the emergency department for COVID-19 pneumonia, confirmed infection by RT-PCR from nasopharyngeal and/or throat swab, ages 70 and below, and Italian speakers. Intervention Setting San Raffaele Hospital	Intervention Group 15 participants received cognitive remediation therapy (CRT) for 2 months. Control Group 30 non-treated participants were matched to CRT patients based on cognitive function baselines.	Cognition • Brief Assessment of Cognition in Schizophrenia (BACS) Depression • Zung Severity Rating Scale (ZSDS) Quality of Life • World Health Organization Quality of Life Assessment (WHOQOL-BREF)	Significant Findings Significant associations were found between ZSDS scores and verbal fluency, working memory, psychomotor coordination, and executive functions. A significant effect of CRT over time was detected for executive functions. There were significant improvements in all patients’ executive function and verbal fluency. Only the intervention group displayed significant improvement in psychomotor coordination. Non-Significant Findings None
Polevaya et al. (2022) Russia	Level 3B Nonrandomized prepost-test study Risk of Bias Moderate	Participants N = 19 (ages 45 to 72 years) Inclusion Criteria Admitted to Volga District Medical Center with post-COVID pneumonia Showed clear signs of post covid syndrome (asthenia, anxiety, depression and stress, as well as a combination of gloomy mood and irritability) Intervention Setting Volga District Medical Center	Intervention Group 19 patients receiving two to four treatment sessions of adaptive neurostimulation (music-like stimuli and rhythmic light stimulation). Participant scores were compared at initial versus final treatment. Control Group None	EEG Reactions • Rhythm reactions • Power shifts Psychological • Stress levels (self-report) • Emotional State (self-report)	Significant Findings Significant difference (p ≤ .05) EEG rhythm reactions between initial and final treatment. Significant (p < .01) increase in power for EEG alpha power shift. The magnitude of these EEG reactions significantly increased with the repetition of treatment sessions, indicating the progressive involvement of adaptive mechanisms and mechanisms of neuro- plasticity in the treatment process. Non-Significant Findings Non-significant increase in power for EEG theta or EEG beta power shifts.
Rabaiotti et al. (2023) Italy	Level 3B Nonrandomized pre-posttest study Risk of Bias Moderate	Participants N = 64 (M age, 67.3 years; 65.6% male) Inclusion Criteria Adults (18+) that have been admitted to the sub-intensive ICU for COVID-19 and developed Post Covid Syndrome (PACS) with or without cognitive impairment. Intervention Setting Rehabilitation Unit of the “Don Gnocchi” Foundation of Parma	Intervention Group 64 PAC patients were treated with a day-by-day individualized psychological intervention consisting of 45 min of cognitive stimulation paired with the standard hospital rehabilitation program. Control Group None	Cognitive • Montreal Cognitive Assessment (MoCA) Psychological • Impact of Event Scale-Revised (IES-R) • Hospital Anxiety and Depression Scale (HADS) A and D • European Quality of Life (EuroQoL) Functional capacity • Barthel Index	Significant Findings 42.8% of patients with cognitive impairments prior to treatment had a complete recovery of cognitive function. 68% showed varying degrees of improvement in cognitive functioning. Significant improvement (p < .0001) in functional capacity as measured by the Barthel Index. Non-significant Findings No significant improvement in the HADS-A, HADS-D, EQoL, IES-R scores, or MoCA scores.
Raunkiaer et al. (2023) Denmark	Level 4 Case Series Risk of Bias Moderate	Participants N = 12 (M age, 50 years; 66.6% female) Inclusion Criteria Referred from a general practitioner or hospital doctor and a visitation by a nurse or OT at REHPA. Hospitalized or isolated at home after being diagnosed with COVID-19 and experienced long-term cognitive deficits that affect their everyday life. Intervention Setting REHPA research clinic	Intervention Group 12 participants were enrolled in the 5-day REHPA rehabilitation program which consisted of cognitive training, compensatory tools, energy conservation, and psychoeducation training. Control group None	Personal insight and knowledge • Being ill and dealing with the long-term effects • Not feeling that they are the same person • Needing time to heal Changed daily routines at home • Managing priorities • Implementing breaks throughout the day • Explaining effects to family members and close relatives Coping with work life • Sufficient reduction in working hours and assignments • Insufficient reduction in working hours and assignments	Significant Findings All 12 participants reported the program helped them gain personal insight and knowledge and stated that their increased insight and knowledge helped modify their daily routines, priorities, and incorporation of breaks. All but one participant reported improvements in coping with work life. Non-Significant Findings None
Sabel et al. (2021) Germany	Level 4 Case Report Risk of Bias Moderate	Participants N = 2 (female; ages 40 and 72 years) Inclusion Criteria Patients experiencing long COVID symptoms Intervention Setting SAVIR-Center in Magdeburg, Germany	Intervention Group Both participants received 10 to 13 sessions lasting 30-45 min of transcranial alternating current stimulation (tACS). They each received currents with a density <2mAmp to the brain and eyes while seated, with a 15 min rest period between sessions. Control Group None	Cognition • Test of Attentional Performance (TAP) • Auditory Verbal Learning Test (AVLT) Visual Field • Oculus Twinfield static perimetry • Humphrey Field Analyzer • High Resolution Perimetry (HRP) Vascularity Dysregulation in the Brain • Dynamic Vascular Analyzer (DVA)	Significant Findings In 3 to 4 days both patients had significant improvements in cognition and partly reversed visual field loss following NIBS. Significant improvement in almost all cognitive domains of TAP, with some having recovered up to 40% to 60% from baseline. Vascular dysregulation significantly improved >300% above baseline in smallest microvessels. Both patients returned to work after therapy. Non-Significant Findings None
Skilbeck (2022) United Kingdom	Level 4 Case Report Risk of bias Moderate	Participants N = 1 (male, age 36) Inclusion criteria Consistent symptoms with long COVID comorbid with depression and anxiety. Intervention setting Telehealth (Microsoft Teams)	Intervention Group One participant received 12 sessions of cognitive behavioral therapy (CBT) over 5 months. Participants’ scores were measured pre-and post-treatment and follow-up. Control group None	Impact of illness on quality of life • COV19-QoL Psychosocial • Patient Health Questionnaire (PHQ-9) • Generalized Anxiety Disorder Assessment (GAD-7) Functional impairment • Work and Social Adjustment Scale (WSAS) Improvement • Improving Access to Psychological Therapies Guide (2008)	Significant Findings CBT intervention for this patient resulted in significant alleviation of symptoms and an improvement in his QoL CBT rehabilitation also led to improved breathing, exercise capacity, muscle strength, and functional outcomes. Non-significant Findings None
Toussaint & Bratty (2023) United States	Level 1B Randomized Control Trial Risk of Bias Low	Participants N = 100 (M age, 43.6 years; 86% female) Inclusion Criteria Individuals ages 21 to 65 suffering from post-viral symptoms at least 3 months after acute COVID-19 infection. Intervention Setting Online workshop	Intervention Group Received neuroplasticity program of Amygdala and Insula Retrainting (AIR) received either online or by mail completed 40-60 min a day. Secondary activities, such as mindfulness meditation and breathing techniques used 20 min throughout the day. Control Group Received general health and well-being online educational program for 12 weeks to wellness.	Fatigue • Multidimensional Fatigue Inventory Health • Short Form Health Survey	Significant Findings The AIR intervention implemented more significant reduction in fatigue and increase in energy than the general health and well-being intervention. Non-significant Findings None
Wilcox & Frank (2021)	Level 4 Case Report Risk of Bias Moderate	Participants N = 1 (female, age 32) Inclusion Criteria Tested positive for COVID-19 and had lingering symptoms of mild infection Intervention Setting: Blended in-person visits at outpatient clinic and remote telehealth services	Intervention Group One participant received gradual cardiovascular endurance training, pursed-lip breathing (PLB), energy conservation, task-specific training and modifications, use of a daily diary, and metacognitive strategies. Control Group None	Activity Tolerance • 1-min sit-to-stand test • Pulse (BPM) • SpO2 (%) • Modified Borg Dyspnea Scale (mBorg) Exertional Dyspnea • SpO2 (%) • Modified Borg Dyspnea Scale (mBorg) Dizziness • Self-reported dizziness episodes Functional Outcomes • Role Checklist • Lawton IADL Scale • AM-PAC 6 Clicks	Significant Findings Improvements were made in symptom severity, functional independence, physical and cognitive performance capacities, and overall energy levels. The participant successfully returned to work. Non-Significant Findings None
Zhang & Zhang (2023) United States	Level 4 Case Report Risk of Bias Moderate	Participants N = 1 (male, age 36) Inclusion Criteria Lingering symptoms of SARS-CoV-2 infection Intervention Setting Not disclosed	Intervention Group One participant receiving 10 sessions of Electro-Magnetic Brain Pulse. Participant’s scores were compared prepost-test. Control Group None	Cognition • Cognitive Testing Battery • Mini Mental State Examination (MMSE) Sensorimotor • Cognitive Testing Battery Sleep • Epworth Sleepiness Scale	Significant Findings Significant changes were identified in decision-making speed (improved by 82%). Slight improvement in hand-eye coordination was noted, as well as improvement in visual acuity. Short term memory decreased 15% to 22%, possibly due to overnight sleep issues. Significant changes were seen in the EEG activation pattern, with increased alpha brain wave activity and decreased delta wave frequency, suggesting possible reduced anxiety and improved cognitive processing capability. Non-Significant Findings No significant change in reaction time, target capture, multiple object tracking, or contrast sensitivity.

Note. ADL, Activities of Daily Living; IADL, Independent Activities of Daily Living.

Intervention Types

Five intervention types emerged from the analysis: (a) cognitive training, (b) cognitive behavioral therapy (CBT), (c) neurostimulation, (d) neurostimulation combined with cognitive training, and (e) multicomponent rehabilitation programs. In addition to these methods, numerous studies highlighted the advantages of personalized, client-centered interventions and assessed using the U.S. Preventive Services Task Force (2012) guidelines.

Cognitive Training

Several studies examined cognitive training for treating long COVID symptoms. Five studies examined the effect of cognitive training on fatigue, physical and mental health, cognitive deficits, and other residual symptoms; two at evidence Level 1B (Hausswirth et al., 2023; Toussaint & Bratty, 2023), one at Level 3B (Duñabeitia et al., 2023), and two at Level 4 (Andrade, 2023; Palladini et al., 2023). Although the study designs varied, all found significant improvements in their experimental groups. Toussaint and Bratty (2023) examined the effect of cognitive training on fatigue secondary to long COVID in 100 participants, ages 21 to 65 years. The experimental group attended a virtual amygdala and insula retraining (AIR) neuroplasticity program. This educational program was designed to interrupt the adverse somatic signals and mental patterns and direct individuals to create new, positive neural pathways that can become perceived by the brain as safe through repetition. Secondary activities were added to support these neuroplasticity techniques. These included mindfulness-based meditation, where individuals focused on the present; alternate nostril breathing, where the individuals were instructed to hold one nostril shut while breathing through the other, then change nostrils and repeat; and other lifestyle therapies, such as providing suggestions for general health supplements and providing ideas for engaging in a calming morning ritual to ease people into their day. The control group received a similarly constructed program focused on general health and wellness. Self-report questionnaires established participants’ baseline and assessed fatigue and quality-of-life factors. Study results found that after 3 months, participants who received AIR had significantly decreased fatigue levels compared with the control group and showed a significant increase in energy levels compared with their control counterparts.

Hausswirth et al. (2023) assessed long COVID symptoms after a neuromodulation program. Thirty-four long COVID participants were randomized into intervention and control groups, whereas 15 unaffected participants comprised the normative group. The intervention group participated in neuromeditation utilizing the Rebalance, a device that provides non-invasive cognitive stimulation and mindfulness training in a zero-gravity position through sound therapy and light stimulation with coach-guided meditation. During a 30-min session, the software adapted the frequency of light stimulations based on the real-time reading of the dominant wave of the participant’s brain at the beginning of the session using a four-channel EEG system (Krigolson et al., 2017). Five frequency levels were used in real-time, which allowed an observed dominant wave to evolve gradually (3–4 min) toward the target brain biorhythm, specifically, the dominant range theta (between 4 and 7 Hz) and the alpha waves (between 8 and 13 Hz). The participant’s adjustments to the device instructions (e.g., attentional focus or body movements) and the device adjustments to the participant’s brain activity (e.g., type and frequency of the stimulation) provided an interactive process. The control and normative groups did not receive interventions (Hausswirth et al., 2023). Progress was noted through self-report questionnaires and their performance in five computerized cognitive tasks. Participants who received the neuromodulation program showed significantly decreased mental and physical fatigue, pain, and mood disturbances, as well as a significant increase in sleep quality compared with both the control and normative groups.

Duñabeitia and colleagues (2023) utilized technology to create a computerized cognitive training (CCT) program to improve cognitive function. This virtual study included 73 participants. Participants completed as much cognitive daily trainings as they desired over 8 weeks, targeting five cognitive domains: reasoning, attention, coordination, memory, and perception. At baseline, participants completed online questionnaires and a Cognitive Assessment Battery (CAB), including 17 tests targeting various cognitive abilities. The CAB results influenced the participants’ assignments and difficulty levels in training courses. The results found cognitive scores increased consistently and showed improvement in all areas of cognition measured after the intervention. Furthermore, intervention time positively correlated with improvements in cognitive performance across all domains. These results were independent of self-reported health or time since COVID-19 infection at baseline.

Andrade (2023) conducted a case study using cognitive training to improve overall daily functioning in one client with long COVID. The client, aged 63 years, was treated as an occupational therapy inpatient to increase reflexive thinking, awareness of present and future situations, habit creation, and independence in basic and instrumental activities of daily living. Observation and the Activity Measure for Post-Acute Care (AM-PAC) were used to track progress. Cognitive training using cognitive strategies was then implemented to improve the perception of occupational performance and to develop new habits. At the end of the 9-day treatment period, the client’s raw AM-PAC score had improved by six points, indicating increased function in activities of daily living. In addition, cognitive strategies aided in the improvement of healthy habits. The client also reported that cognitive strategies increased his perception of daily task performance.

Palladini et al. (2023) compared 15 participants who received cognitive remediation therapy (CRT) over 2 months as outpatients to 30 non-treated participants to determine the efficiency of the intervention on long COVID related cognitive deficits. The Brief Assessment of Cognition in Schizophrenia (BACS) was used to assess cognitive deficits across multiple domains and tailor the CRT program to address each participant’s unique deficits. Also, self-report questionnaires for depressive symptoms and quality-of-life were recorded; however, the quality-of-life assessment was only used in the treated group. The results showed that participants who received CRT had a greater increase in their cognitive performance than their non-treated counterparts. For those who received CRT, the most significant increases occurred in executive function, verbal fluency, and psychomotor coordination. Results also showed that verbal fluency and executive function improvements impacted the participants’ quality of life.

Cognitive Behavioral Therapy

Three studies, one Level 1B (Kuut et al., 2023) and two Level 4 (Bogucki & Sawchuk, 2023; Skilbeck, 2022), utilized CBT for fatigue, PTSD, depression, and anxiety. Kuut et al. (2023) used CBT in a randomized control trial to examine its effectiveness in addressing severe fatigue resulting from COVID-19. One hundred-fourteen participants were randomly assigned in a 1:1 ratio to either receive CBT as part of the intervention group or care as usual (CAU) as part of the control group for 17 weeks. Participants completed the fatigue subscale of the 20-item Checklist Individual Strength (CIS-fatigue) before randomization, after the CBT and CAU period, and at the 6-month follow-up. In addition, secondary measures were evaluated and compared between groups regarding physical functioning, social functioning, somatic symptom severity, and concentrating difficulties. Overall, results of this study demonstrated individuals who experienced severe fatigue from 3 to 12 months post-COVID infection exhibited notably reduced fatigue levels after receiving CBT compared with those who received CAU. Likewise, a significant contrast was found between CBT and CAU groups across all secondary measures, with each measure indicating a preference for the CBT group. Furthermore, effects of CBT persisted for 6 months after the intervention, a significant discovery considering the inconsistent long-term outcomes observed in other CBT studies.

Bogucki and Sawchuk (2023) implemented a weekly cognitive processing therapy (CPT) program for an individual with a PTSD diagnosis along with long COVID in a primary care psychiatric center in the United States of America. The program consisted of 12 sessions of CPT encompassing in- and between-session assignments. CPT was assessed by self-report assessments measuring PTSD, depression, and anxiety symptoms. Throughout treatment, the individual reported a clinically significant reduction in their PTSD symptoms. After treatment, the individual no longer met the diagnostic criteria for PTSD or any other psychiatric disorder.

In a third study, Skilbeck (2022) administered 12 sessions of CBT via telehealth over 5 months to a 36-year-old participant. The participant’s symptoms were ascertained from self-report questionnaires, pre- and post-intervention, with a 3-month follow-up. The application of CBT for this participant led to a substantial reduction in symptoms associated with long COVID in conjunction with depression and anxiety. Moreover, CBT improved job performance, social adjustment, and quality of life.

Neurostimulation

Evidence supporting neurostimulation interventions was limited. One Level 3B and two Level 4 studies examined non-invasive brain stimulation (NIBS) techniques in reducing symptoms attributable to long COVID (Polevaya et al., 2022; Sabel et al., 2021; Zhang & Zhang, 2023). Although implementation and targeted symptoms varied across studies, all found significant improvements in functioning post-intervention compared with the baseline. Polevaya and colleagues (2022) included 19 participants in their study, ages 45 to 72 years, treated in a hospital setting with adaptive neurostimulation. The adaptive neurostimulation consisted of rhythmic photostimulation and music-like stimuli modulated by EEG feedback and monitored outcomes based on rhythm powers and subjective reports. Significant increases from baseline to final EEG rhythm reactions were seen, particularly in the alpha rhythms. Participants self-reported decreased stress levels and improvements in mood; however, no standardized stress or mood assessment was used.

Zhang and Zhang (2023) conducted a case study on a U.S. military base where an electro-magnetic brain pulse protocol was used to treat a 36-year-old male experiencing cognitive slowing, a mildly obstructive pattern of dyspnea, and generalized fatigue. The participant’s cognitive and sensorimotor outcomes were assessed pre-/post-treatment using an extensive cognitive battery and EEG changes. Significant changes occurred in cognition, with an overall improvement of 27% on the cognitive battery. A resting EEG demonstrated significant changes in activation patterns, including increased alpha brain wave activity and a decrease in delta wave frequency. The participant reported decreased “brain fog” and fatigue levels, as well as an increased sense of smell, mood, and ability to breathe. Slight improvements were noted in the ability to fall asleep.

Sabel et al. (2021) used transorbital alternating current stimulation (tACS) to target cognitive and visual impairment in two females with long COVID, aged 40 and 72. Psychological counseling and relaxation techniques were taught in addition to the tACS. Cognition was assessed in both clients via interview, and visual fields were quantified using perimetry pre- and post-therapy. One client underwent additional assessments, including a cognitive battery and a retinal dynamic vascular analyzer (DVA). Post-therapy, both clients reported significant changes in cognitive and visual function, expressing improvements in attention, mental state, memory, feelings of safety, visual clarity and field, and ability to participate in everyday tasks. Increased scores reflected quantifiable visual improvements on the Visual Field Index and visual acuity measures. Also, the client assessed with the DVA showed more than 300% improvement in both artery and vein dilation dynamics. The results of the cognitive battery indicated improvement in almost all cognitive domains including intrinsic and phasic alertness, reaction time, verbal-episodic memory, and cognitive flexibility. However, despite significant improvements, these domains were still below the education and age-based norms.

Neurostimulation Combined With Cognitive Training

The evidence for the use of neurostimulation combined with cognitive training is limited. Two studies, one Level 3B and one Level 4, explored the use of a combined intervention program of NIBS and cognitive training to address cognitive dysfunction in adults’ ages 18 years and older resulting from long COVID (Cavendish et al., 2022; Łuckoś et al., 2021). The duration and implementation of the treatment programs differed; however, both studies found significant differences in cognitive function post-treatment. Łuckoś et al. (2021) provided neurotherapy to a 48-year-old participant at a rehabilitation center. The neurotherapy consisted of two treatments that target neurocognitive dysfunctions following COVID-19. Program A was utilized twice a week for 15 weeks and comprised EEG-neurofeedback with protocols of theta/beta and SMR training on C3 and C4 for strengthening. Program B consisted of goal-oriented cognitive training and was given twice a week for 15 weeks. Strategies for the client to address the late effects of her illness were implemented, such as sleep, exercise, diet, and social connection strategies. Neuropsychological functioning was measured pre- and post-neurotherapy using the standard Polish version of the Mindstreams Interactive Computer Tests. The participant displayed improvements in almost all cognitive functions previously presented with disturbances. Specifically, significant improvements in verbal and non-verbal IQ were seen after the neurotherapy.

Cavendish and colleagues (2022) utilized daily 20-min transcranial direct current stimulation (tDCS) sessions and online cognitive training over 20 days. Four participants, aged 34 to 67 years, received this combined treatment to address cognitive dysfunction resulting from long COVID. The Assessment of PASC inventory (A-PASC) was used to evaluate the client’s cognitive symptoms. The symptoms of depression, processing speed, self-reported executive function, and delayed and immediate recall improved. In addition, self-reported cognitive and emotional symptoms and negative impact on functional abilities decreased.

Multicomponent Rehabilitation Programs

Six studies, three Level 3B and three Level 4 evidence, explored the effectiveness of interdisciplinary and multicomponent approaches to rehabilitating cognition and other associated symptoms of long COVID. Although implementation differed between the studies, all groups receiving interventions experienced an increase in functional outcomes when compared with baseline (García-Molina et al., 2022; Harenwall et al., 2021; Hasting et al., 2023; Rabaiotti et al., 2023; Raunkiaer et al., 2023; Wilcox & Frank, 2021). Rabaiotti and colleagues (2023) provided a rehabilitation program consisting of cognitive stimulation activities, physical aerobic training, and counseling to 64 participants in a rehabilitation center. Cognitive impairments and functional capacity were assessed at admission and discharge using the Montreal Cognitive Assessment (MoCA) and Barthel Index, respectively. Significant findings included increased cognitive function and improvements in functional capacity at discharge.

Hasting et al. (2023) included 33 participants experiencing mild to moderate cognitive impairment, with and without complaints of fatigue, receiving treatment in a hospital program. Treatments included neurorehabilitation, CBT, physiotherapeutic, cognitive, and communicative training. Self-report questionnaires were provided at admission and discharge to assess self-management of symptoms, participation, psychological distress, depressive symptoms, and fatigue. Significant improvements in participants’ mood, self-efficacy, and participation were reported at discharge. However, improvements in fatigue were not observed.

García-Molina and colleagues (2022) used an 8-week outpatient program taking place in the participants’ homes consisting of respiratory therapy, physiotherapy, and neuropsychological rehabilitation to target cognitive and emotional symptomology resulting from long COVID. The cognitive-emotional states of the 123 participants, ages 20 to 81 years, were evaluated at three times: before and after the program and 6 months following treatment. Both the study and control group displayed significant differences when comparing pre- and post-treatment scores. However, the intervention group had larger effect sizes when looking at backward digit span, Rey Auditory Verbal Learning Test (RAVLT), verbal fluency, Hospital Anxiety and Depression Scale (HADS)-anxiety, and HADS-depression. In the 6-month follow-up, the intervention group demonstrated significant improvements in depression and anxiety scores. Finally, when comparing the pre-treatment and follow-up evaluations, the control group displayed improvements between these two times in RAVLT-learning, RAVLT-recall, RAVLT-recognition, and HADS-depression. The study group displayed improvements in RAVLT-learning, RAVLT-recall, and verbal fluency with larger effect sizes in RAVLT-learning and RAVLT-recall.

Wilcox and Frank (2021) conducted a multi-context approach utilizing cognition and occupation-based strategies in symptom self-management training for one participant, age 32 years, experiencing deficits in activity tolerance, sleep hygiene, coping mechanisms, and self-management. Tailored interventions were conducted for 12 weeks in an outpatient clinic combined with remote telehealth services, including cardiovascular endurance training, pursed-lip breathing (PLB), energy conservation, task-specific training, the use of a daily diary, and metacognitive strategies. Self-reported scales of dizziness and a role checklist were used to measure functional outcomes. Functional endurance assessments were completed during weeks 1, 8, and 12. Significant improvements were noted in functional independence, physical and cognitive performance, symptom severity, and successful return to work.

Harenwall and colleagues (2021) implemented a 7-week interdisciplinary program called “Recovering From COVID,” consisting of tailored interventions given virtually to 149 participants. The interventions were targeted at improving sleep, diet, activity management, energy conservation, stress management, and breathing. Significant improvements were noted in participants’ perceived health-related quality of life (HRQoL) across five dimensions: mobility, self-care, usual activities, pain or discomfort, and anxiety or depression.

Raunkiaer et al. (2023) conducted a program at a rehabilitation center consisting of cognitive rehabilitation, ADL training, and psychoeducational support for 12 participants experiencing long-term cognitive effects or barriers to everyday life secondary to long COVID. Three themes emerged through interviewing participants upon discharge: personal insight and knowledge, changed daily routines at home, and coping with work-life balance. All participants reported greater insight and knowledge in modifying daily routines and priorities and incorporating breaks. Of the 12 participants, 11 reported increased work-life coping skills.

Discussion

The results of this review provide occupational therapy practitioners with emerging evidence to guide the treatment of adults with cognitive issues related to long COVID. Five types of intervention to decrease symptoms affecting occupational performance were identified: (a) cognitive training, (b) CBT, (c) neurostimulation, (d) neurostimulation and cognitive training combined, and (e) multicomponent rehabilitation programs. While long COVID research continues, substantial literature reveals its negative impact on daily life. This review found different levels of evidence for the types of cognitive interventions in the scope of occupational therapy practice to improve cognition, mental health, sleep disturbances, and fatigue caused by long COVID.

Cognitive training studies showed strong evidence for impact in a range of long COVID symptoms, including fatigue, sleep quality, cognitive deficits, mental health issues, and functional limitations (Andrade, 2023; Duñabeitia et al., 2023; Hausswirth et al., 2023; Palladini et al., 2023; Toussaint & Bratty, 2023). These findings suggest that cognitive training has a holistic effect on both physical and mental well-being. CBT-based interventions demonstrated moderate evidence by exhibiting reduced anxiety and depressive symptoms, levels of fatigue, PTSD symptoms, and overall enhancement in occupational performance and quality of life (Bogucki & Sawchuk, 2023; Kuut et al., 2023; Skilbeck, 2022). Low-level evidence supported the use of neurostimulation. Participants undergoing neurostimulation experienced increased alpha brain wave activity, indicating a more restful cognitive state, with some reports of increased well-being and mood (Polevaya et al., 2022; Zhang & Zhang, 2023). Although the combination of neurostimulation and cognitive training showed promise with gains in most cognitive domains, the low-level evidence was limited compared with other interventions reviewed (Cavendish et al., 2022; Łuckoś et al., 2021). Although six studies examined multicomponent rehabilitation programs, evidence is considered as low-level because components were inconsistent across studies and because no studies were classified higher than level 3B. Improvements were seen in participation, functional independence, symptom severity, return to work, health-related quality of life, work coping skills, and cognitive and emotional function (García-Molina et al., 2022; Harenwall et al., 2021; Hasting et al., 2023; Rabaiotti et al., 2023; Raunkiaer et al., 2023; Wilcox & Frank, 2021).

Providing evidence-based cognitive rehabilitation is included in the occupational therapy domain (AOTA, 2020). Rather than addressing each domain individually, occupational therapists often address several cognitive performance skills to support clients’ participation in meaningful occupations (Giles et al., 2017). Cognitive training, CBT, neurostimulation and multicomponent rehabilitation programs are within the scope of practice of occupational therapy and have been successfully utilized in many populations. As this review highlights the holistic nature and emerging efficacy of these interventions on long COVID symptoms, practitioners can consider integrating these approaches into their plans of care for individuals with long COVID to address functional cognition and other related deficits.

Incorporating screening tools for functional cognition into the treatment of adults with long COVID can signal the need for cognitive rehabilitation and other interventions across disciplines. Occupational therapists treating individuals with long COVID who screen specifically for functional cognition can further maximize the functional and occupational performance of these individuals (Giles et al., 2017). Practitioners can also utilize recommended outcome measures to guide assessment of adults with long COVID for both clinical and research purposes to holistically address all outcomes areas (Gorst et al., 2023).

The effectiveness of the multi-component programs demonstrates the benefits of interdisciplinary care that incorporates occupational therapy within the treatment practices of long COVID to address functional deficits. As addressing functional cognition is within the scope of occupational therapy practice, occupational therapists can collaborate with other disciplines using combinations of treatment techniques further to alleviate the symptoms of long COVID for adult populations.

Recommendations for Research

Further research is needed to validate, quantify, and refine these approaches and to better understand their long-term effects and broader applications. Higher-level studies examining the effect of cognitive interventions and rehabilitation on long COVID symptoms will strengthen our understanding of the use of these strategies when treating this condition.

A precedent of combining occupational therapy with neurostimulation for improving cognitive and physical function has been established in stroke rehabilitation (Hara et al., 2016). Research into how this could benefit those with long COVID should be explored. Advancements in research comparing other combinations of cognitive interventions and rehabilitation strategies for long COVID symptoms will help clinicians further understand and develop best practices for long COVID symptoms and improve quality of life.

Health inequities can disproportionately increase the risk of negative health outcomes for some groups of people, including women, Hispanic and Latino people, people with more severe COVID-19, transgender people, and people with underlying health conditions (Burns, 2024; CDC, 2024) The access to interventions examined in this review can be impacted by how the social determinants of health (SDOH) impact those with this chronic condition. Individuals living with long COVID may need specialized care, including rehabilitation services, mental health counseling, pulmonary support, ongoing medication management, and monitoring of long-term health complications (Koumpias et al., 2022). SDOH can significantly impact how people seek help, utilize health care resources, and perceive their quality of life within a long COVID context (Lukkahatai et al., 2023). Using the interventions identified in this systematic review and its traditional scope of practice, occupational therapists can reduce and neutralize the effects of SDOH and improve the health outcomes of people living with long COVID. For example, using technology, such as teleneurology assists to overcome some barriers to access, including distance to provider, client-impaired mobility, cognitive function and driving ability, transportation, and time off from work (Towfighi et al., 2023). Future research with a focus on health inequities may further advance our ability to better serve higher-risk groups with long COVID cognitive symptoms.

Limitations and Strengths

Limitations recognized during the evaluation of selected studies include small sample sizes, increased risk of bias, and limited inclusion of control groups. Many studies used multiple interventions complicating comparisons between studies. When critically evaluating the strengths and weaknesses of the included studies, we found each study to be among the most recent and relevant, with publication years of 2021 or later. This review was intended to reflect the current knowledge related to the cognitive interventions and rehabilitation applicable to long COVID symptomatology. However, most studies did not provide the details necessary for accurate reproductions of their intervention processes, limiting the ability of researchers to replicate findings.

During the review process, we attempted to reduce bias by searching all available studies with the guidance of a reference librarian. Despite conducting a systematic literature search following the PRISMA standards, we must acknowledge that this review may not have identified all relevant publications. We utilized the most prominent scientific databases, but some articles may have been overlooked due to the limited selection of databases. In addition, we did not search the gray literature, which may have resulted in the omission of valuable evidence. We cannot eliminate the potential for publication bias, as significant findings are more likely to be published.

This review examined studies from various settings across the continuum of care and included research from various global locations. This makes the conclusions regarding the interventions and rehabilitation techniques more generalizable.

Conclusion

Addressing the impacts of long COVID is essential as COVID-19 persists. The importance lies in understanding how to minimize the everyday effects felt by those living with long COVID. This condition strains a person’s physical, mental, and social health and disrupts their ability to perform their everyday roles and occupations. Although more research is needed focusing on using cognitive interventions and rehabilitation to address long COVID symptoms, these findings aid in informing the delivery and integration of best practices by health care professionals for this emerging chronic condition. The following implications for occupational therapy practice and research have been identified:

Occupational therapy practitioners can enhance the well-being of individuals with long COVID by recognizing the holistic implications of the disease process and the importance of rehabilitation approaches that target a patient’s physical, cognitive, and emotional needs.

Screening for potential cognitive deficits and collaboration with other health care professionals by occupational therapy practitioners will provide more comprehensive, inter-professional care for individuals with long COVID (Gorst et al., 2023).

More research examining the effect of cognitive interventions and rehabilitation on long COVID symptoms with a stronger methodological design is warranted.

Further exploration of varying combinations of cognitive interventions and rehabilitation strategies for long COVID symptoms will further the understanding of best practices for addressing long COVID cognitive symptoms.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethics Statement

Because this is a systematic review, no IRB approval was necessary. This systematic review was registered with Prospero (CRD42023452504). Authors had no conflicts of interest and no funding was received for the completion of the process.

ORCID iDs

Natalie M. Weix

Hannah E. Clingan

Amber Armstead

Claudia Hilton

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Cognitive Interventions and Rehabilitation to Address Long-COVID Symptoms: A Systematic Review

Abstract

Plain Language Summary

Keywords

Method

Protocol

Search Strategy

Selection Criteria

Data Collection

Quality Assessment

Results

Final Studies

Intervention Types

Cognitive Training

Cognitive Behavioral Therapy

Neurostimulation

Neurostimulation Combined With Cognitive Training

Multicomponent Rehabilitation Programs

Discussion

Recommendations for Research

Limitations and Strengths

Conclusion

Footnotes

Declaration of Conflicting Interests

Funding

Ethics Statement

ORCID iDs

References