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

BckgroundLong COVID 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 Long COVID (LC). ObjectivesTo evaluate the psychometric properties of the C19-YRSm in a prospective sample of people with Long COVID. Methods1314 patients attending UK specialist Long COVID clinics completed C19-YRSm and 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 (Cronbachs alpha). Convergent validity was assessed using the FACIT-Fatigue scale. Known groups validity was assessed for the Other Symptoms (OS) subscale as tertiles, 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 instruments two-factor structure. ResultsC19-YRSm demonstrated good scale characteristic properties. Item-total correlations were between 0.37 to 0.65 (for SS and FD), with good internal reliability (Cronbachs alphas >0.8). Item correlations between subscales ranged between 0.46 to 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) and was greater than 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. ConclusionsThe C19-YRSm is a condition-specific, reliable, valid, and responsive patient-reported outcome measure for Long COVID. Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSLong Covid or Post-COVID-19 syndrome is a multisystem, fluctuating condition. C19-YRSm is literatures first condition-specific patient reported outcome measure which needed validation in a large population sample. What this study addsC19-YRSm is a valid, reliable, responsive and easy to administer measure which is able to show clinically meaningful change in the status of the condition in people living with Long Covid. How this study might affect research, practice or policyC19-YRSm can be used in clinical and research settings to reliably capture the condition trajectory and the effect of interventions and also help inform clinical policy.

Post-infection functional gastrointestinal disorders following coronavirus disease-19: A Prospective follow-up cohort study (preprint)

Background:Acute gastrointestinal infections can lead to post-infectious irritable bowel syndrome (PI-IBS). Moreover, coronavirus disease (COVID-19) is related to long-term gastrointestinal sequelae. In this study, the frequency, disease spectrum, and risk factors for post-infection functional gastrointestinal disease (PI-FGID) in COVID-19 patients and healthy controls were prospectively examined. Methods: Validated Rome III and Rome IV questionnaires were used to assess the incidence of PI-FGID in 190 COVID-19 patients, and 160 healthy controls prospectively followed for 1, 3, and 6 months. Results:Six（3.2%）, 1（0.5%）, 3（1.6%）, 5（2.6%）, 6（3.2%）COVID-19 patients had diarrhea, abdominal pain, constipation, dyspepsia and their overlap at 1 month, respectively, while 4（2.1%）, 1（0.5%）, 4（2.1%）, 4（2.1%）, and 6（3.2%）COVID-19 patients had diarrhea, abdominal pain, constipation, dyspepsia and their overlap at three months, respectively. Furthermore, 2（1.3%）, 4（2.5%）, and 3（1.9%）healthy controls developed constipation, dyspepsia, and their overlap at one month, respectively (P=0.193), while 2（1.3%）, 4（2.5%), and 2（1.3%）healthy controls developed constipation, dyspepsia and their overlap at three months, respectively (P=0.286). FGIDs incidence was higher among COVID-19 patients（8.9%) than in healthy controls（3.1%) at 6-month follow-up (P=0.025). Moreover, 7 (3.7%), 5 (2.6%), 3 (1.6%), and 2 (1.1%) COVID-19 patients developed IBS, functional dyspepsia（FD）, functional diarrhea（FDr）, functional constipation（FC）at six months, respectively, while only 2 (1.3%) and 3 (1.9%) healthy controls developed IBS and FD at six months, respectively. Notably, gastrointestinal（GI）symptoms at onset were the independent risk factors for post-COVID-19 FGIDs at six months. Conclusions: COVID-19 increases new-onset PI-FGID at six months compared with healthy controls. GI symptom at the onset of COVID-19 is an independent risk factor for post-COVID-19 FGIDs.

A gene network implicated in the joint-muscle pain, brain fog, chronic fatigue, and bowel irregularity of Ehlers-Danlos and "long" COVID19 syndromes. (preprint)

Objectives Characterization of tissue laxity and dysautonomia symptoms in Ehlers-Danlos syndrome (EDS) uncovered similarities with those of post-infectious SARS-CoV-2 or long COVID19, prompting detailed comparison of their findings and influencing genes. Methods Holistic assessment of 1261 EDS outpatients for 120 history-physical findings populated a deidentified database that includes 568 patients with 317 variant genes obtained by commercial NextGen sequencing. Findings were compared to 15 of long COVID19 compiled in an extensive review, genes to 104 associated with COVID19 severity in multiple molecular studies. Results Fifteen symptoms common to Ehlers-Danlos versus long COVID19 ranged from brain fog (27-80 versus 30-70%), chronic fatigue (38-91; 30-60%), dyspnea (32-52; 29-52%) to irritable bowel (67-89; 14-78%), muscle weakness (22-49; 15-25%), and arthritis (32-94; 15-27%). Genes relevant to EDS included 6 identical to those influencing COVID19 severity (F2, LIFR, NLRP3, STAT1, T1CAM1, TNFRSF13B) and 18 similar including POLG-POLD4, SLC6A2-SLC6A20, and NFKB1-NFKB2. Both gene sets had broad genomic distribution, many mitochondrial genes influencing EDS and many involved with immunity-inflammation modifying COVID19 severity. Recurring DNA variants in EDS that merit evaluation in COVID19 resistance include those impacting connective tissue elements--51 in COL5 (joint), 29 in COL1/2/9/11 (bone), 13 in COL3 (vessel), and 18 in FBN1 (vessel-heart)--or neural function--93 in mitochondrial DNA, 28 in COL6/12, 16 in SCN9A/10A/11A, 14 in POLG, and 11 in genes associated with porphyria. Conclusions Holistic ascertainment of finding pattern and exome variation in EDS defined tissue laxity, neuromuscular, and autonomic correlations that transcend single abnormalities or types. Implied networks of nuclear and mitochondrial genes are linked to findings like brain fog, fatigue, and frailty in EDS, their similarity to long COVID19 supporting shared therapies for disorders affecting a minimum 0.1% of the global population.