Psychometric analysis of the modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) in a prospective multicentre study

Background: Long COVID (LC) is a novel multisystem clinical syndrome affecting millions of individuals worldwide. The modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) is a condition-specific patient-reported outcome measure designed for assessment and monitoring of people with LC. Objectives: To evaluate the psychometric properties of the C19-YRSm in a prospective sample of people with LC. Methods: 1314 patients attending 10 UK specialist LC clinics completed C19-YRSm and EuroQol 5D-5L (EQ-5D-5L) longitudinally. Scale characteristics were derived for C19-YRSm subscales (Symptom Severity (SS), Functional Disability (FD) and Overall Health (OH)) and internal consistency (Cronbach’s alpha). Convergent validity was assessed using the Functional Assessment of Chronic Illness Therapy (FACIT)—Fatigue Scale. Known groups validity was assessed for the Other Symptoms subscale as tertiles, as well as by hospitalisation and intensive care admission. Responsiveness and test–retest reliability was evaluated for C19-YRSm subscales and EQ-5D-5L. The minimal important difference (MID) and minimal clinically important difference (MCID) were estimated. Confirmatory factor analysis was applied to determine the instrument’s two-factor structure. Results: C19-YRSm demonstrated good scale characteristic properties. Item-total correlations were between 0.37 and 0.65 (for SS and FD), with good internal reliability (Cronbach’s alphas>0.8). Item correlations between subscales ranged between 0.46 and 0.72. Convergent validity with FACIT was good (−0.46 to −0.62). The three subscales discriminated between different levels of symptom burden (p<0.001) and between patients admitted to hospital and intensive care. There was moderate responsiveness for the three subscales ranging from 0.22 (OH) to 0.50 (SS) which was greater than for the EQ-5D-5L. Test–retest reliability was good for both SS 0.86 and FD 0.78. MID was 2 for SS, 2 for FD and 1 for OH; MCID was 4 for both the SS and FD. The factor analysis supported the two-factor SS and FD structure. Conclusions: The C19-YRSm is a condition-specific, reliable, valid and responsive patient-reported outcome measure for LC

Long COVID clinical severity types based on symptoms and functional disability: A longitudinal evaluation

Background: Long COVID (LC) is a multisystem clinical syndrome with functional disability and compromised overall health. Information on LC clinical severity types is emerging in cross-sectional studies. This study explored the pattern and consistency of long COVID (LC) clinical severity types over time in a prospective sample. Methods: Participants with LC completed the condition-specific outcome measure C19-YRSm (Yorkshire Rehabilitation Scale modified version) at two assessment time points. A cluster analysis for clinical severity types was undertaken at both time points using the k-means partition method. Results: The study included cross-sectional data for 759 patients with a mean age of 46.8 years (SD = 12.7), 69.4% females, and a duration of symptoms of 360 days (IQR 217 to 703 days). The cluster analysis at first assessment revealed three distinct clinical severity type clusters: mild (n = 96), moderate (n = 422), and severe (n = 241). Longitudinal data on 356 patients revealed that the pattern of three clinical severity types remained consistent over time between the two assessments, with 51% of patients switching clinical severity types between the assessments. Conclusions: This study is the first of its kind to demonstrate that the pattern of three clinical severity types is consistent over time, with patients also switching between severity types, indicating the fluctuating nature of LC

Physical, cognitive and social triggers of symptom fluctuations in people living with long COVID: an intensive longitudinal cohort study

Background: Symptom fluctuations within and between individuals with long COVID are widely reported, but the extent to which severity varies following different types of activity and levels of exertion, and the timing of symptoms and recovery, have not previously been quantified. We aimed to characterise timing, severity, and nature of symptom fluctuations in response to effortful physical, social and cognitive activities, using Ecological Momentary Assessments. Methods: We recorded activity, effort, and severity of 8 core symptoms every 3 h for up to 24 days, in cohorts from both clinic and community settings. Symptom severities were jointly modelled using autoregressive and moving average processes. Findings: Consent was received from 376 participants providing ≥1 week's measurements (273 clinic-based, 103 community-based). Severity of all symptoms was elevated 30 min after all categories of activity. Increased effort was associated with increased symptom severity. Fatigue severity scores increased by 1.8/10 (95% CI: 1.6–1.9) following the highest physical exertions and by 1.5 (1.4–1.7) following cognitive efforts. There was evidence of only mild delayed fatigue 3 h (0.3, 0.2–0.5) or one day later (0.2, 0.0– 0.5). Fatigue severity increased as the day progressed (1.4, 1.0–1.7), and cognitive dysfunction was 0.2 lower at weekends (0.1–0.3). Interpretation Cognitive, social, self-care and physical activities all triggered increased severity across every symptom, consistent with associated common pathways as potential therapeutic targets. Clear patterns of symptom fluctuations emerged that support more targeted self-management

Prevalence of orthostatic intolerance in Long Covid clinic patients: a multicentre observational study

Orthostatic intolerance (OI), including postural orthostatic tachycardia syndrome (PoTS) and orthostatic hypotension (OH), are often reported in long covid, but published studies are small with inconsistent results. We sought to estimate the prevalence of objective OI in patients attending long covid clinics and healthy volunteers and associations with OI symptoms and comorbidities. Participants with a diagnosis of long covid were recruited from eight UK long covid clinics, and healthy volunteers from general population. All undertook standardized National Aeronautics and Space Administration Lean Test (NLT). Participants' history of typical OI symptoms (e.g., dizziness, palpitations) before and during the NLT were recorded. Two hundred seventy-seven long covid patients and 50 frequency-matched healthy volunteers were tested. Healthy volunteers had no history of OI symptoms or symptoms during NLT or PoTS, 10% had asymptomatic OH. One hundred thirty (47%) long covid patients had previous history of OI symptoms and 144 (52%) developed symptoms during the NLT. Forty-one (15%) had an abnormal NLT, 20 (7%) met criteria for PoTS, and 21 (8%) had OH. Of patients with an abnormal NLT, 45% had no prior symptoms of OI. Relaxing the diagnostic thresholds for PoTS from two consecutive abnormal readings to one abnormal reading during the NLT, resulted in 11% of long covid participants (an additional 4%) meeting criteria for PoTS, but not in healthy volunteers. More than half of long covid patients experienced OI symptoms during NLT and more than one in 10 patients met the criteria for either PoTS or OH, half of whom did not report previous typical OI symptoms. We therefore recommend all patients attending long covid clinics are offered an NLT and appropriate management commenced

Health-related quality of life in Long COVID: Mapping the condition-specific C19-YRSm measure onto the EQ-5D-5L

Background: Long Covid (LC) is a clinical syndrome of persistent, fluctuating symptoms subsequent to COVID-19 infection with a prevalence global estimate of many millions of cases. LC has significant detrimental effects on health-related quality of life (HRQoL), activities of daily living (ADL), and work productivity. Condition-specific patient-reported outcome measures (PROMs), such as the modified Covid-19 Yorkshire Rehabilitation Scale (C19-YRSm), have been developed to capture the impact of LC. However, these do not provide health utility data required for cost-utility analyses of LC interventions. The aim of this study was therefore to derive a mapping algorithm for the C19-YRSm to enable health utilities to be generated from this PROM. Methods: Data were collected from a large study evaluating LC services in the UK. A total of 1434 people with LC had completed both the C19-YRSm and the EQ-5D-5L on the same day. The EQ-5D-5L responses were then converted to EQ-5D-3L utility scores. Correlation and linear regression analyses were applied to determine items from the C19-YRSm and covariates for inclusion in the algorithm. Model fit, mean differences across the range of EQ-5D-3L scores (-0.59 to 1), and Bland-Altman plots were used to evaluate the algorithm. Responsiveness (standardised response mean; SRM) of the mapped utilities was also investigated on a subset of participants with repeat assessments (N=85). Results: There was a strong level of association between 8 items and 2 domains on the C19-YRSm with the EQ-5D single-item dimensions. These related to joint pain, muscle pain, anxiety, depression, walking/moving around, personal care, ADL, and social role, as well as Overall Health and Other Symptoms. Model fit was good (R2 = 0.7). The mean difference between the actual and mapped scores was < 0.10 for the range from 0 to 1 indicating a good degree of targeting for positive values of the EQ-5D-3L. The SRM for the mapped EQ-5D-3L health utilities (based on the C19-YRSm) was 0.37 compared to 0.17 for the observed EQ-5D-3L utility scores, suggesting the mapped EQ-5D-3L is more responsive to change. Conclusions: We have developed a simple, responsive, and robust mapping algorithm to enable EQ-5D-3L health utilities to be generated from 10 items of the C19-YRSm. This mapping algorithm will facilitate economic evaluations of interventions, treatment, and management of people with LC, as well as further helping to describe and characterise patients with LC irrespective of any treatment and interventions

Digital home-monitoring for capturing daily fluctuation of symptoms; a longitudinal repeated measures study: Long Covid Multi-disciplinary Consortium to Optimise Treatments and Services across the NHS (A LOCOMOTION Study): a study protocol

Introduction A substantial proportion of COVID-19 survivors continue to have symptoms more than 3 months after infection, especially of those who required medical intervention. Lasting symptoms are wide-ranging, and presentation varies between individuals and fluctuates within an individual. Improved understanding of undulation in symptoms and triggers may improve efficacy of healthcare providers and enable individuals to better self-manage their Long Covid. We present a protocol where we aim to develop and examine the feasibility and usability of digital home monitoring for capturing daily fluctuation of symptoms in individuals with Long Covid and provide data to facilitate a personalised approach to the classification and management of Long Covid symptoms. Methods and analysis This study is a longitudinal prospective cohort study of adults with Long Covid accessing 10 National Health Service (NHS) rehabilitation services in the UK. We aim to recruit 400 people from participating NHS sites. At referral to study, 6 weeks and 12 weeks, participants will complete demographic data (referral to study) and clinical outcome measures, including ecological momentary assessment (EMA) using personal mobile devices. EMA items are adapted from the COVID-19 Yorkshire Rehabilitation Scale items and include self-reported activities, symptoms and psychological factors. Passive activity data will be collected through wrist-worn sensors. We will use latent class growth models to identify trajectories of experience, potential phenotypes defined by co-occurrence of symptoms and inter-relationships between stressors, symptoms and participation in daily activities. We anticipate that n=300 participants provide 80% power to detect a 20% improvement in fatigue over 12 weeks in one class of patients relative to another. Ethics and dissemination The study was approved by the Yorkshire & The Humber—Bradford Leeds Research Ethics Committee (ref: 21/YH/0276). Findings will be disseminated in peer-reviewed publications and presented at conferences. Trial registration number ISRCTN15022307

Physical, cognitive, and social triggers of symptom fluctuations in people living with long COVID: an intensive longitudinal cohort study

Background: Symptom fluctuations within and between individuals with long COVID are widely reported, but the extent to which severity varies following different types of activity and levels of exertion, and the timing of symptoms and recovery, have not previously been quantified. We aimed to characterise timing, severity, and nature of symptom fluctuations in response to effortful physical, social and cognitive activities, using Ecological Momentary Assessments. Methods: We recorded activity, effort, and severity of 8 core symptoms every 3 h for up to 24 days, in cohorts from both clinic and community settings. Symptom severities were jointly modelled using autoregressive and moving average processes. Findings: Consent was received from 376 participants providing ≥1 week's measurements (273 clinic-based, 103 community-based). Severity of all symptoms was elevated 30 min after all categories of activity. Increased effort was associated with increased symptom severity. Fatigue severity scores increased by 1.8/10 (95% CI: 1.6–1.9) following the highest physical exertions and by 1.5 (1.4–1.7) following cognitive efforts. There was evidence of only mild delayed fatigue 3 h (0.3, 0.2–0.5) or one day later (0.2, 0.0– 0.5). Fatigue severity increased as the day progressed (1.4, 1.0–1.7), and cognitive dysfunction was 0.2 lower at weekends (0.1–0.3). Interpretation Cognitive, social, self-care and physical activities all triggered increased severity across every symptom, consistent with associated common pathways as potential therapeutic targets. Clear patterns of symptom fluctuations emerged that support more targeted self-management