Detecting Orthostatic Intolerance in Long COVID in a Clinic Setting.

INTRODUCTION: A likely mechanism of Long COVID (LC) is dysautonomia, manifesting as orthostatic intolerance (OI). In our LC service, all patients underwent a National Aeronautics and Space Administration (NASA) Lean Test (NLT), which can detect OI syndromes of Postural Tachycardia Syndrome (PoTS) or Orthostatic Hypotension (OH) in a clinic setting. Patients also completed the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS), a validated LC outcome measure. Our objectives in this retrospective study were (1) to report on the findings of the NLT; and (2) to compare findings from the NLT with LC symptoms reported on the C19-YRS. METHODS: NLT data, including maximum heart rate increase, blood pressure decrease, number of minutes completed and symptoms experienced during the NLT were extracted retrospectively, together with palpitation and dizziness scores from the C19-YRS. Mann-Witney U tests were used to examine for statistical difference in palpitation or dizziness scores between patients with normal NLT and those with abnormal NLT. Spearman's rank was used to examine the correlation between the degree of postural HR and BP change with C19-YRS symptom severity score. RESULTS: Of the 100 patients with LC recruited, 38 experienced symptoms of OI during the NLT; 13 met the haemodynamic screening criteria for PoTS and 9 for OH. On the C19-YRS, 81 reported dizziness as at least a mild problem, and 68 for palpitations being at least a mild problem. There was no significant statistical difference between reported dizziness or palpitation scores in those with normal NLT and those with abnormal NLT. The correlation between symptom severity score and NLT findings was <0.16 (poor). CONCLUSIONS: We have found evidence of OI, both symptomatically and haemodynamically in patients with LC. The severity of palpitations and dizziness reported on the C19-YRS does not appear to correlate with NLT findings. We would recommend using the NLT in all LC patients in a clinic setting, regardless of presenting LC symptoms, due to this inconsistency.

Non-Pharmacological Therapies for Post-Viral Syndromes, Including Long COVID: A Systematic Review.

BACKGROUND: Post-viral syndromes (PVS), including Long COVID, are symptoms sustained from weeks to years following an acute viral infection. Non-pharmacological treatments for these symptoms are poorly understood. This review summarises the evidence for the effectiveness of non-pharmacological treatments for PVS. METHODS: We conducted a systematic review to evaluate the effectiveness of non-pharmacological interventions for PVS, as compared to either standard care, alternative non-pharmacological therapy, or placebo. The outcomes of interest were changes in symptoms, exercise capacity, quality of life (including mental health and wellbeing), and work capability. We searched five databases (Embase, MEDLINE, PsycINFO, CINAHL, MedRxiv) for randomised controlled trials (RCTs) published between 1 January 2001 to 29 October 2021. The relevant outcome data were extracted, the study quality was appraised using the Cochrane risk-of-bias tool, and the findings were synthesised narratively. FINDINGS: Overall, five studies of five different interventions (Pilates, music therapy, telerehabilitation, resistance exercise, neuromodulation) met the inclusion criteria. Aside from music-based intervention, all other selected interventions demonstrated some support in the management of PVS in some patients. INTERPRETATION: In this study, we observed a lack of robust evidence evaluating the non-pharmacological treatments for PVS, including Long COVID. Considering the prevalence of prolonged symptoms following acute viral infections, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological treatments for patients with PVS. REGISTRATION: The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.

Post-COVID syndrome and adults with intellectual disability: another vulnerable population forgotten?

An area of interest presently is the lingering symptoms after COVID-19, i.e. post-COVID-19 syndrome (PCS). Specifics of diagnosis and management of PCS are emerging. However, vulnerable populations such as those with intellectual disabilities, who were disproportionately affected by the pandemic, risk being 'left behind' from these considerations.

Effect of using a structured pacing protocol on post-exertional symptom exacerbation and health status in a longitudinal cohort with the post-COVID-19 syndrome.

BACKGROUND: Post Exertional Symptom Exacerbation (PESE) is a characteristic symptom of Post-COVID Syndrome (PCS). OBJECTIVES: This prospective study investigated the effect of a 6-week structured World Health Organisation (WHO) Borg CR-10 5-phase pacing protocol on PESE episodes and quality of life in a cohort of individuals with long-standing PCS (average duration of symptoms was 17 months). METHODS: Participants received weekly telephone calls with a clinician to complete the Leeds PESE Questionnaire (LPQ) and identify the appropriate phase of the pacing protocol. EQ-5D 5L was completed at the intervention's beginning and end to measure overall health. RESULTS: Thirty-one participants completed the 6-week protocol, with a statistically and clinically significant reduction in the average number of PESE episodes (from 3.4 episodes in week one to 1.1 in week six), with an average decrease of 16% (95% CI: 9% to 24%; p<0.001) each week, and reduction across all three exertional triggers (physical, cognitive, and emotional). Physical activity levels showed moderate improvements during the intervention period. Mean EQ-5D 5L scores improved from 51.4 points to 60.6 points (paired difference of 9.2 points, 95% CI: 3.2 to 15.2 points; p=0.004). CONCLUSIONS: A structured pacing protocol significantly reduces PESE episodes and improves overall health in PCS. This article is protected by copyright. All rights reserved.

Towards evidence-based and inclusive models of peer support for long covid: A hermeneutic systematic review.

Since the first wave of COVID-19 in March 2020 the number of people living with post-COVID syndrome has risen rapidly at global pace, however, questions still remain as to whether there is a hidden cohort of sufferers not accessing mainstream clinics. This group are likely to be constituted by already marginalised people at the sharp end of existing health inequalities and not accessing formal clinics. The challenge of supporting such patients includes the question of how best to organise and facilitate different forms of support. As such, we aim to examine whether peer support is a potential option for hidden or hardly reached populations of long COVID sufferers with a specific focus on the UK, though not exclusively. Through a systematic hermeneutic literature review of peer support in other conditions (57 papers), we evaluate the global potential of peer support for the ongoing needs of people living with long COVID. Through our analysis, we highlight three key peer support perspectives in healthcare reflecting particular theoretical perspectives, goals, and understandings of what is 'good health', we call these: biomedical (disease control/management), relational (intersubjective mutual support) and socio-political (advocacy, campaigning & social context). Additionally, we identify three broad models for delivering peer support: service-led, community-based and social media. Attention to power relations, social and cultural capital, and a co-design approach are key when developing peer support services for disadvantaged and underserved groups. Models from other long-term conditions suggest that peer support for long COVID can and should go beyond biomedical goals and harness the power of relational support and collective advocacy. This may be particularly important when seeking to reduce health inequalities and improve access for a potentially hidden cohort of sufferers.

HEART rate variability biofeedback for long COVID symptoms (HEARTLOC): protocol for a feasibility study.

INTRODUCTION: Long COVID (LC), also known as post-COVID-19 syndrome, refers to symptoms persisting 12 weeks after COVID-19 infection. It affects up to one in seven people contracting the illness and causes a wide range of symptoms, including fatigue, breathlessness, palpitations, dizziness, pain and brain fog. Many of these symptoms can be linked to dysautonomia or dysregulation of the autonomic nervous system after SARS-CoV2 infection. This study aims to test the feasibility and estimate the efficacy, of the heart rate variability biofeedback (HRV-B) technique via a standardised slow diaphragmatic breathing programme in individuals with LC. METHODS AND ANALYSIS: 30 adult LC patients with symptoms of palpitations or dizziness and an abnormal NASA Lean Test will be selected from a specialist Long COVID rehabilitation service. They will undergo a 4-week HRV-B intervention using a Polar chest strap device linked to the Elite HRV phone application while undertaking the breathing exercise technique for two 10 min periods everyday for at least 5 days a week. Quantitative data will be gathered during the study period using: HRV data from the chest strap and wrist-worn Fitbit, the modified COVID-19 Yorkshire Rehabilitation Scale, Composite Autonomic Symptom Score, WHO Disability Assessment Schedule and EQ-5D-5L health-related quality of life measures. Qualitative feedback on user experience and feasibility of using the technology in a home setting will also be gathered. Standard statistical tests for correlation and significant difference will be used to analyse the quantitate data. ETHICS AND DISSEMINATION: The study has received ethical approval from Health Research Authority (HRA) Leicester South Research Ethics Committee (21/EM/0271). Dissemination plans include academic and lay publications. TRIAL REGISTRATION NUMBER: NCT05228665.

A Mixed-Methods Evaluation of a Virtual Rehabilitation Program for Self-Management in Post-COVID-19 Syndrome (Long COVID).

Long COVID (LC) symptoms can be long standing, diverse and debilitating; comprehensive multidisciplinary rehabilitation programs are required to address this. A 10-week LC Virtual Rehabilitation Program (VRP) was developed to provide early education and self-management techniques to address the main symptoms of LC and was delivered to a group of persons with Long COVID (PwLC) online, facilitated by members of the multi-disciplinary rehabilitation team. This paper describes an evaluation of this VRP. Questionnaires completed by Healthcare Professionals (HCP) delivering the VRP were thematically analyzed to gain a priori themes and design semi-structured telephone interview questions for PwLC. Template analysis (TA) was used to analyze interview data. Routinely collected patient demographics and service data were also examined. Seventeen HCP survey responses were obtained and 38 PwLC telephone questionnaires were completed. The HCP interviews generated three a priori themes (1. Attendance and Availability, 2. Content, 3. Use of Digital Technology). TA was applied and three further themes emerged from the combined HCP and PwLC responses (4. Group Dynamics, 5. Individual Factors, 6. Internal Change). Key outcomes demonstrated that: the VRP was highly valued; digital delivery enabled self-management; barriers to attendance included work/life balance, use of technology, health inequalities; and LC was poorly understood by employers. Recommendations are provided for the design of VRPs for LC.

Cardiovascular magnetic resonance imaging and spectroscopy in clinical long-COVID-19 syndrome: a prospective case-control study.

BACKGROUND: The underlying pathophysiology of post-coronavirus disease 2019 (long-COVID-19) syndrome remains unknown, but increased cardiometabolic demand and state of mitochondrial dysfunction have emerged as candidate mechanisms. Cardiovascular magnetic resonance (CMR) provides insight into pathophysiological mechanisms underlying cardiovascular disease and 31-phosphorus CMR spectroscopy (31P-CMRS) allows non-invasive assessment of the myocardial energetic state. The main aim of the study was to assess whether long COVID-19 syndrome is associated with abnormalities of myocardial structure, function, perfusion and energy metabolism. METHODS: Prospective case-control study. A total of 20 patients with a clinical diagnosis of long COVID-19 syndrome (seropositive) and no prior underlying cardiovascular disease (CVD) and 10 matching healthy controls underwent 31P-CMRS and CMR at 3T at a single time point. All patients had been symptomatic with acute COVID-19, but none required hospital admission. RESULTS: Between the long COVID-19 syndrome patients and matched contemporary healthy controls there were no differences in myocardial energetics (phosphocreatine to ATP ratio), in cardiac structure (biventricular volumes), function (biventricular ejection fractions, global longitudinal strain), tissue characterization (T1 mapping and late gadolinium enhancement) or perfusion (myocardial rest and stress blood flow, myocardial perfusion reserve). One patient with long COVID-19 syndrome showed subepicardial hyperenhancement on late gadolinium enhancement imaging compatible with prior myocarditis, but no accompanying abnormality in cardiac size, function, perfusion, extracellular volume fraction, native T1, T2 or cardiac energetics. CONCLUSIONS: In this prospective case-control study, the overwhelming majority of patients with a clinical long COVID-19 syndrome with no prior CVD did not exhibit any abnormalities in myocardial energetics, structure, function, blood flow or tissue characteristics.

Clinical Characteristics and Mechanisms of Musculoskeletal Pain in Long COVID.

Objective: Musculoskeletal (MSK) pain is being increasingly reported by patients as one of the most common persistent symptoms in post-COVID-19 syndrome or Long COVID. However, there is a lack of understanding of its prevalence, characteristics, and underlying pathophysiological mechanisms. The objective of this review is to identify and describe the features and characteristics of MSK pain in Long COVID patients. Methods: The narrative review involved a literature search of the following online databases: MEDLINE (OVID), EMBASE (OVID), CINAHL, PsyclNFO, and Web of Science (December 2019 to February 2022). We included observational studies that investigated the prevalence, characteristics, risk factors and mechanisms of MSK pain in Long COVID. After screening and reviewing the initial literature search results, a total of 35 studies were included in this review. Results: The overall reported prevalence of MSK pain in Long COVID ranged widely from 0.3% to 65.2%. The pain has been reported to be localized to a particular region or generalized and widespread. No consistent pattern of progression of MSK pain symptoms over time was identified. Female gender and higher BMI could be potential risk factors for Long COVID MSK pain, but no clear association has been found with age and ethnicity. Different pathophysiological mechanisms have been hypothesized to contribute to MSK pain in Long COVID including increased production of proinflammatory cytokines, immune cell hyperactivation, direct viral entry of neurological and MSK system cells, and psychological factors. Conclusion: MSK pain is one of the most common symptoms in Long COVID. Most of the current literature on Long COVID focuses on reporting the prevalence of persistent MSK pain. Studies describing the pain characteristics are scarce. The precise mechanism of MSK pain in Long COVID is yet to be investigated. Future research must explore the characteristics, risk factors, natural progression, and underlying mechanisms of MSK pain in Long COVID.

Cardiovascular magnetic resonance imaging in patients with clinical post-covid-19 syndrome

150 Table 1Comparison of 31P-MRS and CMR findings between patients with Post-COVID-19 syndrome and healthy volunteersVariable Healthy volunteers (n=10) Post-COVID-19 Syndrome (n=19) p-value PCr/ATP ratio 2.11±0.5 2.24±0.4 0.49 LV end diastolic volume index (ml/m2) 87±20 81±10 0.43 LV ejection fraction (%) 64±4 61±4 0.07 RV end diastolic volume index (ml/m2) 93±23 83±13 0.24 RV ejection fraction (%) 55±8 57±6 0.49 Global longitudinal strain (%) -13.3±2.3 -11.9±3.7 0.21 Mean T1 (ms) 1206±64 1158±114 0.15 Extra-cellular volume (%) 25±2.3 22±4.5 0.03 T2 (ms) 39±2.4 40±2.9 0.46 MPR 3.1±0.9 3.0±0.8 0.89 Continuous variables are expressed as mean (SD) or median (IQR) and categorical variables as number (%). PCr/ATP=phosphocreatine and adenosine triphosphate ratio;LV=left ventricular;ml/m2=milliliters per square meter of body surface area;RV=right ventricular;ms=milliseconds;MPR=myocardial perfusion reserve. 150 Figure 1Evaluation of Cardiac Involvement in Post COVID-19 Syndrome[Figure omitted. See PDF]Conflict of InterestNone

Construct Validity and Responsiveness of the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS) in a Cohort of Italian Hospitalized COVID-19 Patients.

Post-COVID Syndrome (PCS) is characterized by physical, psychological and cognitive symptoms with a negative impact on daily activities. This study tested the responsiveness and construct validity of the original version of the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS) in a cohort of Italian hospitalized COVID-19 patients. This longitudinal study involved 79 hospitalized COVID-19 patients with rehabilitation needs, assessed after 12 and 26 weeks post-infection. Functional and patient-reported outcome measures were correlated with 10 items of the C19-YRS to test the construct validity, whereas distribution-based methods were used for the responsiveness over time. After 12 weeks since infection, 88.5% of patients reported fatigue, 83.3% breathlessness, 69.4% anxiety, 55.6% depression, and 44.9% pain. Moreover, 84.6% experienced reduced mobility, 75.7% had difficulties with usual activities, and 47.4% with personal care. Single items for each symptom had significant correlation (rho 0.25-0.60) with well-established scales for these symptoms. At 26 weeks, except for anxiety, all the PCS symptoms were still present but significantly reduced. The C19-YRS had moderate responsiveness for the most represented deficit reported. The C19-YRS was a valuable patient-reported outcome for screening, assessing severity, and monitoring the persistence of symptoms after 12 and 26 weeks from SARS-CoV2 infection in a cohort of Italian hospitalized patients.

The modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) patient-reported outcome measure for Long Covid or Post-COVID-19 syndrome.

BACKGROUND: The C19-YRS is the literature's first condition-specific, validated scale for patient assessment and monitoring in Post-COVID-19 syndrome (PCS). The 22-item scale's subscales (scores) are symptom severity (0-100), functional disability (0-50), additional symptoms (0-60), and overall health (0-10). OBJECTIVES: This study aimed to test the scale's psychometric properties using Rasch analysis and modify the scale based on analysis findings, emerging information on essential PCS symptoms, and feedback from a working group of patients and professionals. METHODS: Data from 370 PCS patients were assessed using a Rasch Measurement Theory framework to test model fit, local dependency, response category functioning, differential item functioning, targeting, reliability, and unidimensionality. The working group undertook iterative changes to the scale based on the psychometric results and including essential symptoms. RESULTS: Symptom severity and functional disability subscales showed good targeting and reliability. Post hoc rescoring suggested that a 4-point response category structure would be more appropriate than an 11-point response for both subscales. Symptoms with binary responses were placed in the other symptoms subscale. The overall health single-item subscale remained unchanged. CONCLUSION: A 17-item C19-YRSm was developed with subscales (scores): symptom severity (0-30), functional disability (0-15), other symptoms (0-25), and overall health (0-10).

LOng COvid Multidisciplinary consortium Optimising Treatments and servIces acrOss the NHS (LOCOMOTION): protocol for a mixed-methods study in the UK.

INTRODUCTION: Long COVID, a new condition whose origins and natural history are not yet fully established, currently affects 1.5 million people in the UK. Most do not have access to specialist long COVID services. We seek to optimise long COVID care both within and outside specialist clinics, including improving access, reducing inequalities, helping self-management and providing guidance and decision support for primary care. We aim to establish a 'gold standard' of care by systematically analysing current practices, iteratively improving pathways and systems of care. METHODS AND ANALYSIS: This mixed-methods, multisite study is informed by the principles of applied health services research, quality improvement, co-design, outcome measurement and learning health systems. It was developed in close partnership with patients (whose stated priorities are prompt clinical assessment; evidence-based advice and treatment and help with returning to work and other roles) and with front-line clinicians. Workstreams and tasks to optimise assessment, treatment and monitoring are based in three contrasting settings: workstream 1 (qualitative research, up to 100 participants), specialist management in 10 long COVID clinics across the UK, via a quality improvement collaborative, experience-based co-design and targeted efforts to reduce inequalities of access, return to work and peer support; workstream 2 (quantitative research, up to 5000 participants), patient self-management at home, technology-supported monitoring and validation of condition-specific outcome measures and workstream 3 (quantitative research, up to 5000 participants), generalist management in primary care, harnessing electronic record data to study population phenotypes and develop evidence-based decision support, referral pathways and analysis of costs. Study governance includes an active patient advisory group. ETHICS AND DISSEMINATION: LOng COvid Multidisciplinary consortium Optimising Treatments and servIces acrOss the NHS study is sponsored by the University of Leeds and approved by Yorkshire & The Humber-Bradford Leeds Research Ethics Committee (ref: 21/YH/0276). Participants will provide informed consent. Dissemination plans include academic and lay publications, and partnerships with national and regional policymakers. TRIAL REGISTRATION NUMBER: NCT05057260, ISRCTN15022307.

The Relationship between Physical Activity and Long COVID: A Cross-Sectional Study.

The relationship between Long Covid (LC) symptoms and physical activity (PA) levels are unclear. In this cross-sectional study, we examined this association, and the advice that individuals with LC received on PA. Adults with LC were recruited via social media. The New Zealand physical activity questionnaire short form (NZPAQ-SF) was adapted to capture current and pre-COVID-19 PA levels and activities of daily living (ADLs). Participants reported how PA affected their symptoms, and what PA recommendations they had received from healthcare professionals and other resources; 477 participants completed the survey. Mean age (SD) was 45.69 (10.02) years, 89.1% female, 92.7% white, and median LC duration was 383.5 days (IQR: 168.25,427). Participants were less active than pre-COVID-19 (26.88 ± 74.85 vs. 361.68 ± 396.29 min per week, p < 0.001) and required more assistance with ADLs in a 7-day period compared to pre-COVID-19 (2.23 ± 2.83 vs. 0.11 ± 0.74 days requiring assistance, p < 0.001). No differences were found between the number of days of assistance required with ADLs, or the amount of PA, and the different durations of LC illness (p > 0.05). Participants reported the effect of PA on LC symptoms as: worsened (74.84%), improved (0.84%), mixed effect (20.96%), or no effect (28.72%). Participants received contradictory advice on whether to be physically active in LC. LC is associated with a reduction in PA and a loss of independence, with most participants reporting PA worsened LC symptoms. PA level reduction is independent of duration of LC. Research is needed to understand how to safely return to PA without worsening LC symptoms.

Non-pharmacological therapies for postviral syndromes, including Long COVID: a systematic review and meta-analysis protocol.

INTRODUCTION: Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as 'post COVID-19 syndrome', 'post-COVID condition' or more commonly 'Long COVID'. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments. AIMS: This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies. METHODS AND ANALYSIS: Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported. ETHICS AND DISSEMINATION: This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups. PROSPERO REGISTRATION NUMBER: The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).

Making Best Use of Home-Based Rehabilitation Robots

Large-scale clinical trials have shown that rehabilitation robots are as affective as conventional therapy, but the cost-effectiveness is preventing their uptake. This study investigated whether a low-cost rehabilitation robot could be deployed in a home setting for rehabilitation of people recovering from stroke (n = 16) and whether clinical outcome measures correlated well with kinematic measures gathered by the robot. The results support the feasibility of patients independently using the robot with improvement in both clinical measures and kinematic data. We recommend using kinematic data early in an intervention to detect improvement while using a robotic device. The kinematic measures in the assessment task (hits/minute and normalised jerk) adequately pick up changes within a four-week period, thus allowing the rehabilitation regime to be adapted to suit the user’s needs. Estimating the long-term clinical benefit must be explored in future research.