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ImportanceMulti-organ impairment associated with Long COVID is a significant burden to individuals, populations and health systems, presenting challenges for diagnosis and care provision. Standardised assessment across multiple organs over time is lacking, particularly in non-hospitalised individuals.ObjectiveTo determine the prevalence of organ impairment in Long COVID patients at 6 and at 12 months after initial symptoms and to explore links to clinical presentation.DesignThis was a prospective, longitudinal study in individuals following recovery from acute COVID-19. We assessed symptoms, health status, and multi-organ tissue characterisation and function, using consensus definitions for single and multi-organ impairment. Physiological and biochemical investigations were performed at baseline on all individuals and those with organ impairment were reassessed, including multi-organ MRI, 6 months later.SettingTwo non-acute settings (Oxford and London).Participants536 individuals (mean 45 years, 73% female, 89% white, 32% healthcare workers, 13% acute COVID-19 hospitalisation) completed baseline assessment (median: 6 months post-COVID-19). 331 (62%) with organ impairment or incidental findings had follow up, with reduced symptom burden from baseline (median number of symptoms: 10 and 3, at 6 and 12 months).ExposureSARS-CoV-2 infection 6 months prior to first assessment.Main outcomePrevalence of single and multi-organ impairment at 6 and 12 months post-COVID-19.ResultsExtreme breathlessness (36% and 30%), cognitive dysfunction (50% and 38%) and poor health-related quality of life (EQ-5D-5LConclusion and RelevanceOrgan impairment was present in 59% of individuals at 6 months post-COVID-19, persisting in 59% of those followed up at 1 year, with implications for symptoms, quality of life and longer-term health, signalling need for prevention and integrated care of Long COVID.Trial RegistrationClinicalTrials.govIdentifier:NCT04369807Key pointsQuestion: What is the prevalence of organ impairment in Long COVID at 6- and 12-months post-COVID-19?Findings: In a prospective study of 536 mainly non-hospitalised individuals, symptom burden decreased, but single organ impairment persisted in 59% at 12 months post-COVID-19.Meaning: Organ impairment in Long COVID has implications for symptoms, quality of life and longer-term health, signalling need for prevention and integrated care of Long COVID.

To describe the burden of post-COVID respiratory sequelae in posthospital and nonhospitalized COVID-19 survivors and to describe the priorities of clinical management.Due to varying definitions of 'Long COVID' or 'Post-COVID', the prevalence of post-COVID sequelae or persisting symptoms is challenging to estimate but ranges from 2.3 to 51%. Risk factors for persistent post-COVID symptoms include age, female sex, deprivation, presence of comorbidities; and in posthospital COVID-19 survivors, the severity of acute infection. Common post-COVID respiratory symptoms include breathlessness, cough and chest pain and many individuals also experience exercise intolerance. The most common pulmonary function test abnormality is impaired diffusing capacity for carbon monoxide. In posthospital COVID-19 survivors, the prevalence of interstitial lung damage is 5-11%. Disordered breathing is common in all post-COVID patients and respiratory physiotherapy is helpful.The vast numbers of COVID-19 infections globally implies that a large number of people will be affected by post-COVID sequelae even with conservative estimates. A significant number of people are affected for several months and up to years following acute infection. Post-COVID sequelae have a detrimental impact on quality of life and ability to work.

RATIONALE: Shared symptoms and genetic architecture between COVID-19 and lung fibrosis suggests SARS-CoV-2 infection may lead to progressive lung damage.OBJECTIVES: The UKILD Post-COVID study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 based on risk strata.METHODS: The Post-HOSPitalisation COVID Study (PHOSP-COVID) was used for capture of routine and research follow-up within 240 days from discharge. Thoracic CTs linked by PHOSP-COVID identifiers were scored for percentage of residual lung abnormalities (ground glass opacities and reticulations). Risk factors in linked CT were estimated with Bayesian binomial regression and risk strata were generated. Numbers within strata were used to estimate post-hospitalization prevalence using Bayesian binomial distributions. Sensitivity analysis was restricted to participants with protocol driven research follow-up.MEASUREMENTS AND MAIN RESULTS: The interim cohort comprised 3700 people. Of 209 subjects with linked CTs (median 119 days, interquartile range 83-155), 166 people (79.4%) had >10% involvement of residual lung abnormalities. Risk factors included abnormal chest X-ray (RR 1·21 95%CrI 1·05; 1·40), percent predicted DLcoCONCLUSIONS: Residual lung abnormalities were estimated in up to 11% of people discharged following COVID-19 related hospitalization. Health services should monitor at-risk individuals to elucidate long-term functional implications. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease trajectory. The aim of this study was to assess the potential of neutrophil-to-lymphocyte ratio (NLR) to predict outcomes in IPF.We adopted a two-stage discovery (n = 71) and validation (n = 134) design using patients from the UCL partners (UCLp) cohort. We then combined discovery and validation cohorts and included an additional 794 people with IPF, using real-life data from 5 other UK centers, to give a combined cohort of 999 patients. Data were collected from patients presenting over a 13-year period (2006-2019) with mean follow up of 3.7 years (censoring: 2018-2020).In the discovery analysis, we showed that high values of NLR (/ = 2.9 vs 2.9) were associated with increased risk of mortality in IPF (HR 2.04, 95% CI 1.09-3.81, n = 71, p = 0.025). This was confirmed in the validation (HR 1.91, 95% CI 1.15-3.18, n = 134, p = 0.0114) and combined cohorts (HR 1.65, n = 999, 95% CI 1.39-1.95; p 0·0001). NLR correlated with GAP stage and GAP index (p 0.0001). Stratifying patients by NLR category (low/high) showed significant differences in survival for GAP stage 2 (p 0.0001), however not for GAP stage 1 or 3. In a multivariate analysis, a high NLR was an independent predictor of mortality/progression after adjustment for individual GAP components and steroid/anti-fibrotic use (p 0·03). Furthermore, incorporation of baseline NLR in a modified GAP-stage/index, GAP-index/stage-plus, refined prognostic ability as measured by concordance (C)-index.We have identified NLR as a widely available test that significantly correlates with lung function, can predict outcomes in IPF and refines cohort staging with GAP. NLR may allow timely prioritisation of at-risk patients, even in the absence of lung function.Breathing Matters, GSK, CF Trust, BLF-Asthma, MRC, NIHR Alpha-1 Foundation.

Background Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients. Methods and results One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms). Conclusions During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.

Pressure on acute medical services in the pandemic mandated an assertive emergency department (ED) discharge policy. Given the potential for subsequent deterioration and growing appreciation of complications relating to COVID-19 infection, this follow up study was instigated to provide clinical reassurance that discharged patients had followed a safe clinical course. 199 patients discharged from the ED of our central London hospital were identified over a 20-day period at the height of the pandemic in April 2020. 44 had already reattended ED and 12 had been admitted. At 2-week telephone follow-up, 14 patients were identified who required urgent recall for assessment. At 4-week telephone follow-up, 87 patients were identified with persistent symptoms requiring face to face review. A COVID-19 follow-up clinic was therefore established to provide multi-professional review and diagnostics. 65 patients attended for this assessment. This is the first report on outcomes in COVID-19 infected patients discharged from an ED. It highlights the importance of safety-netting after discharge, the difficulty in predicting which patients might deteriorate and the need for appropriate follow up services.

The COVID-19 pandemic has necessitated rapid adaptation of healthcare providers to new clinical and logistical challenges. Following identification of high levels of emergency department (ED) reattendance among patients with suspected COVID-19 at our centre, we piloted a rapid remote follow-up service for this patient group. We present our service framework and evaluation of our pilot cohort of 192 patients. We followed up patients by telephone within 36 hours of their ED attendance. Pulse oximetry was used for remote monitoring of a subset of patients. Patients required between one and six consecutive telephone assessments, dependent on illness severity, and 23 patients were recalled for in-person assessment. Approximately half of patients with confirmed or probable COVID-19 required onward referral for respiratory follow-up. This framework reduced unplanned ED reattendances in comparison with a retrospective comparator cohort (4.7% from 22.6%). We reproduced these findings in a validation cohort with a high prevalence of acute COVID-19, managed through the clinic in September–October 2020, where we identified an unplanned ED reattendance rate of 5.2%. We propose that rapid remote follow-up is a mechanism by which ambulatory patients can be clinically supported during the acute phase of illness, with benefits both to patient care and to health service resilience.

SummaryBackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease trajectory. The aim of this study was to assess the potential of neutrophil-to-lymphocyte ratio (NLR) to predict outcomes for people with IPF.MethodWe adopted a two-stage discovery and validation design using patients from the UCL partners (UCLp) cohort. For the discovery analysis, we included 71 patients from UCLH. In the validation analysis, we included 928 people with IPF, using real-life data from UCLH and 5 other UK centres. Data were collected from patients presenting over a 13-year period with a mean follow up time of 3.7 years.FindingsIn the discovery analysis, we showed that values of NLR (/=2.9) were associated with increased risk of mortality (HR 2.04, 95% CI 1.09-3.81; p=0.025). In the validation cohort we confirmed this association of high NLR with mortality (HR 1.65, 95% CI 1.39-1.95; pInterpretationWe have identified NLR as a widely available test that significantly correlates with lung function, can predict outcomes in IPF and refines clinical GAP-staging. NLR may help ILD specialist centres prioritise at risk patients in a timely way, even in the absence of lung function.

IntroductionAs mortality rates from COVID-19 disease fall, the high prevalence of long-term sequelae (Long COVID) is becoming increasingly widespread, challenging healthcare systems globally. Traditional pathways of care for Long Term Conditions (LTCs) have tended to be managed by disease-specific specialties, an approach that has been ineffective in delivering care for patients with multi-morbidity. The multi-system nature of Long COVID and its impact on physical and psychological health demands a more effective model of holistic, integrated care. The evolution of integrated care systems (ICSs) in the UK presents an important opportunity to explore areas of mutual benefit to LTC, multi-morbidity and Long COVID care. There may be benefits in comparing and contrasting ICPs for Long COVID with ICPs for other LTCs.Methods and analysisThis study aims to evaluate health services requirements for ICPs for Long COVID and their applicability to other LTCs including multi-morbidity and the overlap with medically not yet explained symptoms (MNYES). The study will follow a Delphi design and involve an expert panel of stakeholders including people with lived experience, as well as clinicians with expertise in Long COVID and other LTCs. Study processes will include expert panel and moderator panel meetings, surveys, and interviews. The Delphi process is part of the overall STIMULATE-ICP programme, aimed at improving integrated care for people with Long COVID.Ethics and disseminationEthical approval for this Delphi study has been obtained (Research Governance Board of the University of York) as have approvals for the other STIMULATE-ICP studies. Study outcomes are likely to inform policy for ICPs across LTCs. Results will be disseminated through scientific publication, conference presentation and communications with patients and stakeholders involved in care of other LTCs and Long COVID.RegistrationResearchregistry: https://www.researchregistry.com/browse-the-registry#home/registrationdetails/6246bfeeeaaed6001f08dadc/.

BackgroundLong Covid is associated with multiple symptoms and impairment in multiple organs. Cardiac impairment has been reported to varying degrees by varying methodologies in cross-sectional studies. Using cardiac magnetic resonance (CMR), we investigated the 12-month trajectory of cardiac impairment in individuals with Long Covid.Methods534 individuals with Long Covid underwent baseline CMR (T1 and T2 mapping, cardiac mass, volumes, function, and strain) and multi-organ MRI at 6 months (IQR 4.3,7.3) since first post-COVID-19 symptoms and 330 were rescanned at 12.6 (IQR 11.4, 14.2) months if abnormal findings were reported at baseline. Symptoms, standardised questionnaires, and blood samples were collected at both timepoints. Cardiac impairment was defined as one or more of: low left or right ventricular ejection fraction (LVEF and RVEF), high left or right ventricular end diastolic volume (LVEDV and RVEDV), low 3D left ventricular global longitudinal strain (GLS), or elevated native T1 in ≥3 cardiac segments. A significant change over time was reported by comparison with 92 healthy controls.ResultsThe technical success of this multiorgan assessment in non-acute settings was 99.1% at baseline, and 98.3% at follow up, with 99.6% and 98.8% for CMR respectively. Of individuals with Long Covid, 102/534 [19%] had cardiac impairment at baseline; 71/102 had complete paired data at 12 months. Of those, 58% presented with ongoing cardiac impairment at 12 months. High sensitivity cardiac troponin I and B-type natriuretic peptide were not predictive of CMR findings, symptoms, or clinical outcomes. At baseline, low LVEF, high RVEDV and low GLS were associated with cardiac impairment. Low LVEF at baseline was associated with persistent cardiac impairment at 12 months.ConclusionCardiac impairment, other than myocarditis, is present in 1 in 5 individuals with Long Covid at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers are unable to identify cardiac impairment in Long COVID. Subtypes of disease (based on symptoms, examination, and investigations) and predictive biomarkers are yet to be established. Interventional trials with pre-specified subgroup analyses are required to inform therapeutic options.

COVID-19, caused by SARS-CoV-2, is an emerging viral respiratory pathogen. The disease was first described in China in 2019, likely emerging as a zoonosis, before spreading worldwide to cause a severe global pandemic in 2020. COVID-19 is transmitted person to person, predominantly by droplet spread. COVID-19 causes a wide spectrum of clinical illness ranging from asymptomatic infection, to a mild self-limiting illness. A small proportion of individuals will go on to develop a more severe respiratory illness which may be complicated by acute respiratory distress syndrome. The majority of individuals will make a full recovery but a minority of patients will have a more severe outcome. Age is the strongest predictor of outcomes with mortality increasing to 15% or higher among those aged 80 years or older. Treatment options for COVID-19 continue to evolve. The strongest current evidence is the use of systemic corticosteroids which reduce mortality in patients with moderate to severe COVID-19. Given the epidemic nature of COVID-19 early surge planning and expansion of both staff and bed base capacity are critical. At the time of writing a number of promising COVID-19 vaccines have been developed but the long term impact of these vaccines on the pandemic is uncertain.

Post-COVID syndrome (PCS), or long COVID, is an increasingly recognized complication of acute SARS-CoV-2 infection, characterized by persistent fatigue, reduced exercise tolerance, chest pain, shortness of breath, and cognitive slowing. Acute COVID-19 is strongly linked with an increased risk of thrombosis, which is a prothrombotic state quantified by an elevated von Willebrand factor (VWF) antigen (Ag)/ADAMTS13 ratio that is associated with severity of acute COVID-19 infection. We investigated whether patients with PCS also had evidence of a prothrombotic state associated with symptom severity. In a large cohort of patients referred to a dedicated post-COVID-19 clinic, thrombotic risk, including VWF(Ag)/ADAMTS13 ratio, was investigated. An elevated VWF(Ag)/ADAMTS13 ratio (≥1.5) was present in nearly one-third of the cohort and was 4 times more likely to be present in patients with impaired exercise capacity, as evidenced by desaturation ≥3% and/or an increase in lactate level >1 from baseline on a 1-minute sit-to-stand test and/or a 6-minute walk test (P < .0001). Of 276 patients, 56 (20%) had impaired exercise capacity, of which 55% (31/56) had a VWF(Ag)/ADAMTS13 ratio ≥1.5 (P < .0001). Factor VIII and VWF(Ag) were elevated in 26% and 18%, respectively, and support a hypercoagulable state in some patients with PCS. These findings suggest possible ongoing microvascular/endothelial dysfunction in the pathogenesis of PCS and suggest a role for antithrombotic therapy in the treatment of these patients.

IntroductionPost-COVID-19 complications require simultaneous characterisation and management to plan policy and health system responses. We describe the 12-month experience of the first UK dedicated post-COVID-19 clinical service to include hospitalised and non-hospitalised patients.MethodsIn a single-centre, observational analysis, we report the demographics, symptoms, comorbidities, investigations, treatments, functional recovery, specialist referral and rehabilitation of 1325 individuals assessed at the University College London Hospitals post-COVID-19 service between April 2020 and April 2021, comparing by referral route: posthospitalised (PH), non-hospitalised (NH) and post emergency department (PED). Symptoms associated with poor recovery or inability to return to work full time were assessed using multivariable logistic regression.Results1325 individuals were assessed (PH: 547, 41.3%; PED: 212, 16%; NH: 566, 42.7%). Compared with the PH and PED groups, the NH group were younger (median 44.6 (35.6–52.8) years vs 58.3 (47.0–67.7) years and 48.5 (39.4–55.7) years), more likely to be female (68.2%, 43.0% and 59.9%), less likely to be of ethnic minority (30.9%, 52.7% and 41.0%) or seen later after symptom onset (median (IQR): 194 (118–298) days, 69 (51–111) days and 76 (55–128) days; all pConclusionPost-COVID-19 symptoms were significant in PH and NH patients, with significant ongoing healthcare needs and utilisation. Trials of interventions and patient-centred pathways for diagnostic and treatment approaches are urgently required.

Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding UK Research and Innovation and National Institute for Health Research.

IntroductionThe COVID-19 pandemic has led to over 100 million cases worldwide. The UK has had over 4 million cases, 400 000 hospital admissions and 100 000 deaths. Many patients with COVID-19 suffer long-term symptoms, predominantly breathlessness and fatigue whether hospitalised or not. Early data suggest potentially severe long-term consequence of COVID-19 is development of long COVID-19-related interstitial lung disease (LC-ILD).Methods and analysisThe UK Interstitial Lung Disease Consortium (UKILD) will undertake longitudinal observational studies of patients with suspected ILD following COVID-19. The primary objective is to determine ILD prevalence at 12 months following infection and whether clinically severe infection correlates with severity of ILD. Secondary objectives will determine the clinical, genetic, epigenetic and biochemical factors that determine the trajectory of recovery or progression of ILD. Data will be obtained through linkage to the Post-Hospitalisation COVID platform study and community studies. Additional substudies will conduct deep phenotyping. The Xenon MRI investigation of Alveolar dysfunction Substudy will conduct longitudinal xenon alveolar gas transfer and proton perfusion MRI. The POST COVID-19 interstitial lung DiseasE substudy will conduct clinically indicated bronchoalveolar lavage with matched whole blood sampling. Assessments include exploratory single cell RNA and lung microbiomics analysis, gene expression and epigenetic assessment.Ethics and disseminationAll contributing studies have been granted appropriate ethical approvals. Results from this study will be disseminated through peer-reviewed journals.ConclusionThis study will ensure the extent and consequences of LC-ILD are established and enable strategies to mitigate progression of LC-ILD.

Introduction: British Thoracic Society (BTS) guidelines recommend assessment of breathing pattern disorder (BPD) for ongoing breathlessness post COVID-19 infection. Breathing pattern retraining (BPR) has been shown to improve breathlessness arising from BPD. Aim: Ascertain percentage of people with BPD in a post-COVID clinic cohort. To determine if virtual BPR improves breathlessness in patients with BPD following COVID-19 infection. Method:: Data was collected from patients completing a systematic MDT assessment in a post-COVID clinic. Breathlessness (Dyspnoea 12- D12) and breathing pattern (Brompton Breathing Pattern Assessment Tool - BPAT) were assessed by the clinic Physiotherapist and on completion of BPR. Those with MDT diagnosis of BPD were referred for physiotherapy led virtual BPR. A Wilcoxon Sign Rank test was used to compare pre and post treatment data. The effect sizes were presented as a Hedge’s G statistic. Effect sizes are classified as: small > 0.2; moderate > 0.5; large > 0.8. Results: 55 of 293 patients were diagnosed with BPD (18.8%). Data for 17 patients who completed virtual BPR were analysed. Mean number of days since symptoms onset was 61.88 (SD 19.72). Patients completed a mean of 3.74 (SD 1.19) BPR sessions. Improvement in D12 was statistically significant (median pre 18, post 5, (z=-3.62, p=0.000)). The effect size was large: Hedge’s G=1.84. Improvement in BPAT was statistically significant (median BPAT pre 4 post 1, (z=-3.66, p=0.000)). The effect size was large: Hedge’s G=3.19. Conclusion: BPD is prevalent post COVID. Virtual BPR improves breathing pattern and breathlessness.

BackgroundComplications following SARS-CoV-2 infection require simultaneous characterisation and management to plan policy and health system responses. We describe the 12-month experience of the first UK dedicated Post-COVID clinical service to include both hospitalised and non-hospitalised patients.MethodsIn a single-centre, observational analysis, we report outcomes for 1325 individuals assessed in the University College London Hospitals NHS Foundation Trust Post-COVID service between April 2020 and April 2021. Demography, symptoms, comorbidities, investigations, treatments, functional recovery, specialist referral and rehabilitation were compared by referral route (“post hospitalisation”, PH; “non-hospitalised”, NH; and “post emergency department”, PED). Symptoms associated with poor recovery or inability to return to work full-time were assessed using multivariable logistic regression.Findings1325 individuals were assessed (PH 547 [41.3%], PED 212 [16%], NH 566 [42.7%]. Compared with PH and PED groups, NH were younger (median 44.6 [35.6-52.8] vs 58.3 [47.0-67.7] and 48.5 [39.4-55.7] years), more likely to be female (68.2%, 43.0% and 59.9%), less likely to be from an ethnic minority (30.9%, 52.7% and 41.0%) and seen later after symptom onset (median [IQR]:194 [118-298], 69 [51-111] and 76 [55-128] days) (all pInterpretationSymptoms following SARS-CoV-2 infection were significant in both post- and non-hospitalised patients, with significant ongoing healthcare needs and utilisation. Trials of interventions and patient-centred pathways for diagnostic and treatment approaches are urgently required.FundingUCLH/UCL BRCResearch in contextPrevious evidenceLong COVID and post-COVID syndrome were first identified in April 2020. We searched PubMed and medrxiv for articles published up to April 30th, 2021, using the keywords “long COVID”, “post-COVID syndrome”, “persistent symptoms”, “hospitalised”, “community” and “non-hospitalised”. We identified 17 articles and 7 systematic reviews. Fifteen studies have considered symptoms, multi-organ or functional impairment but only one study to-date has considered all these variables in non-hospitalised COVID patients. No studies have compared symptom burden and management between non-hospitalised and hospitalised individuals as systematically assessed and managed in a dedicated post-COVID service.Added value of this studyFor the first time, we report the baseline characteristics, investigation and outcomes of initial assessment of all eligible patients in a dedicated multi-professional post-COVID service, including 547 post-hospitalisation, 566 non-hospitalised and 212 patients discharged from emergency department. Despite relatively low comorbidity and risk factor burden in non-hospitalised patients, we show that both non-hospitalised and hospitalised patients presenting with persistent symptoms after SARS-CoV2 infection have high rates of functional impairment, specialist referral and rehabilitation, even 6-12 months after the acute infection. These real-world data will inform models of care during and beyond the pandemic.Implications of all the available evidenceThe significant, long-lasting health and social consequences of SARS-CoV-2 infection are not confined to those who required hospitalisation. As with other long-term conditions, care of patients experiencing Long COVID or specific end-organ effects require consistent, integrated, patient-centred approaches to investigation and management. At public health and policy level, burden of post-COVID morbidity demands renewed focus on effective infection suppression for all age groups.

Post-coronavirus disease 19 (COVID-19) syndrome has substantial health and economic implications. It is multi-systemic, with prevalent autonomic symptoms. Understanding presentations and potential autonomic causes may help guide treatment strategies and recovery.All patients with a suspected or confirmed history of COVID-19 infection who underwent autonomic testing between May 2020 and October 2021 were reviewed retrospectively.We evaluated 62 patients (20 male, 42 female, mean age of 41.38 ±11.52). COVID-19 was PCR confirmed in 15 patients (26%), and five (8%) required acute hospital intervention. Most common symptoms included palpitations (81%), light-headedness/dizziness (62%), dyspnoea (48%), fatigue (46%), or cognitive symptoms(33%)Autonomic testing showed normal blood pressure responses to pressor stimuli, a mean respiratory sinus arrhythmia of 18.89b/m, and Valsalva ratio of 2.09. Postural tachycardia syndrome (PoTS) was diagnosed in 12 patients, autonomically mediated syncope (AMS) in 11, neurogenic orthostatic hypotension (NOH) in two, and initial orthostatic hypotension (IOH) in seven.Normal supine and upright plasma noradrenaline levels were measured in 34 patients (mean 283.38 pg/ml supine; 472.43pg/ml tilted).Autonomic testing was reassuring (PoTS and syncope) in the majority with abnormal testing (n=32, or 52%). Further phenotyping of PoTS to exclude neuropathic pathology may be needed. IOH and OH are important considerations.

IntroductionThe profile of neurological disorders post-SARS-CoV-2 remains unclear. We describe obser- vations from a SARS-CoV-2 neurology clinic established to meet demand.MethodsA retrospective case-note review of consecutive patients attending a SARS-CoV2 neurology clinic over a 6-month period was conducted. Demographics, clinical features, medications and inves- tigation results were collected.ResultsThere were 122 patients included (78 female: 44 male, median age 44 years); all met WHO criteria for probable or confirmed SARS-CoV2 infection and 15.6% were hospitalised. Most frequently reported symptoms included fatigue (82.0%), cognitive disturbance (63.9%) and headache (63.9%). Attentional deficits were the most common observation on formal neuropsychometry and were associated with fatigue, sleep-impairment, migraine and anxiety symptoms (pConclusionThe majority of patients had normal brain imaging and showed improvement. Further research is required to look into the biological mechanisms underlying neurological symptoms in SARS-CoV2 including in those not hospitalised for their initial illness.

The aim of this study was to assess the temporal evolution of pulmonary

Large numbers of people are being discharged from hospital following COVID-19 without assessment of recovery. In 384 patients (mean age 59.9 years; 62% male) followed a median 54 days post discharge, 53% reported persistent breathlessness, 34% cough and 69% fatigue. 14.6% had depression. In those discharged with elevated biomarkers, 30.1% and 9.5% had persistently elevated d-dimer and C reactive protein, respectively. 38% of chest radiographs remained abnormal with 9% deteriorating. Systematic follow-up after hospitalisation with COVID-19 identifies the trajectory of physical and psychological symptom burden, recovery of blood biomarkers and imaging which could be used to inform the need for rehabilitation and/or further investigation.

IntroductionLong COVID-19 is a distressing, disabling and heterogeneous syndrome often causing severe functional impairment. Predominant symptoms include fatigue, cognitive impairment (‘brain fog’), breathlessness and anxiety or depression. These symptoms are amenable to rehabilitation delivered by skilled healthcare professionals, but COVID-19 has put severe strain on healthcare systems. This study aims to explore whether digitally enabled, remotely supported rehabilitation for people with long COVID-19 can enable healthcare systems to provide high quality care to large numbers of patients within the available resources. Specific objectives are to (1) develop and refine a digital health intervention (DHI) that supports patient assessment, monitoring and remote rehabilitation; (2) develop implementation models that support sustainable deployment at scale; (3) evaluate the impact of the DHI on recovery trajectories and (4) identify and mitigate health inequalities due to the digital divide.Methods and analysisMixed-methods, theoretically informed, single-arm prospective study, combining methods drawn from engineering/computer science with those from biomedicine. There are four work packages (WP), one for each objective. WP1 focuses on identifying user requirements and iteratively developing the intervention to meet them; WP2 combines qualitative data from users with learning from implementation science and normalisation process theory, to promote adoption, scale-up, spread and sustainability of the intervention; WP3 uses quantitative demographic, clinical and resource use data collected by the DHI to determine illness trajectories and how these are affected by use of the DHI; while WP4 focuses on identifying and mitigating health inequalities and overarches the other three WPs.Ethics and disseminationEthical approval obtained from East Midlands – Derby Research Ethics Committee (reference 288199). Our dissemination strategy targets three audiences: (1) Policy makers, Health service managers and clinicians responsible for delivering long COVID-19 services; (2) patients and the public; (3) academics.Trial registration numberResearch Registry number: researchregistry6173.

Introduction Idiopathic pulmonary fibrosis (IPF) often leads to death from respiratory failure, but there is much variation in outcome between patients. Limited evidence suggests an independent relationship between body weight change and mortality in patients with IPF.1,2 Other prognostic biomarkers aid clinical decision making, and it is recognised that a decline in Forced Vital Capacity (FVC) of >10% in a year is a significant predictor of mortality in this disease. Objectives To explore if weight loss independently affects mortality in individuals with IPF. Methods Retrospective data were collected using electronic medical records on a sample of patients diagnosed with IPF at one tertiary care NHS teaching hospital in London, UK. Adult (≥18 y) patients diagnosed with IPF were included. Weight was collected at diagnosis and around 1 year after diagnosis together with details of comorbidities, medications, oxygen use, echocardiogram and pulmonary function tests. A significant body weight loss was defined as an annual body weight change of >5%.2 Survival from 1 year after diagnosis onwards served as a primary endpoint in a multivariable Cox regression model. Results A total of 205 patients diagnosed with IPF between 01/2017 and 12/2018 were included in the analysis. The mean age at diagnosis was 75.4±8.2 years and 172/205 (83.9%) were male. Median survival was 1172 days (95% CI 756 to 1589). Percent weight loss of 5% or more was associated with a shorter survival time (median 556 vs. 1548) compared to those who lost less weight. In the multivariable Cox regression model, only TLCO percent predicted at 1 year (p Conclusions Weight loss of 5% or more is independently associated with increased mortality of IPF patients. References Alakhras M, et al. Body mass index and mortality in patients with idiopathic pulmonary fibrosis. Chest. The American College of Chest Physicians, 2007;131(5):1448–1453. doi: 10.1378/chest.06–2784 Nakatsuka Y, et al. The clinical significance of body weight loss in idiopathic pulmonary fibrosis patients. Respiration 2018;96(4):338–347. doi: 10.1159/000490355

Introduction Nintedanib, one of two approved antifibrotic treatments for patients with IPF, is a tyrosine-kinase inhibitor whose inhibition of vascular endothelial growth factor poses a theoretical bleeding risk. Bleeding events were reported in 10% of patients in clinical trials1 despite excluding patients at risk of bleeding including those on con-current anticoagulation (AC) or antiplatelet (AP) therapy. Consequently, Nintedanib is relatively contraindicated for patients with IPF on AC/AP treatment. Methods We performed a retrospective analysis to examine bleeding risk within a tertiary-care ILD centre in the UK. Patients make an informed choice of anti-fibrotic and Nintedanib is offered even if patients are on AC/AP. Bleeding events were defined as intracranial, lower or upper gastrointestinal (GI) or respiratory tract (haemoptysis/epistaxis). Due to widespread prophylactic use of aspirin in both groups this was excluded from the analysis. Results Of 317 patients with IPF (median age 76 years, 83% male), 118 (37%) were on Nintendanib and 79 (25%) on Pirfenidone. The remaining patients (48%) were outside criteria for, or had not tolerated, antifibrotic therapy. There were no significant differences in baseline characteristics. In the Nintedanib group 21 (17.8%) patients were also on an AC/AP: Warfarin (n=6), DOACs (n=6), dalteparin (n=2) and clopidogrel (n=7). This compared to 11 (13.9%) patients in the Pirfenidone group: Warfarin (n=1), DOACs (n=5) and clopidogrel (n=5). Of the 21 patients on an AC/AP in the Nintedanib group 1 (4%) had a bleeding complication (lower GI bleed on a DOAC), compared to none in the Pirfenidone group. There were no deaths in either group. Conclusion Our results from real-life data demonstrate that 17.8% of our patients with IPF are on AC/AP and the overall incident of bleeding events in those patients taking both Nintedanib and an AC/AP, is similar to that reported for Nintedanib alone1. Our results suggest that con-current AC/AP doesn’t increase bleeding risk and shouldn’t be a reason to withhold Nintedanib. Further larger observational studies are needed to explore this risk further. References European Medicines Agency. Ofev (nintedanib): EU product summary. 2015. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003821/WC500182474.pdf. Accessed 15th July 2019.

Objective To assess medium-term organ impairment in symptomatic individuals following recovery from acute SARS-CoV-2 infection. Design Baseline findings from a prospective, observational cohort study. Setting Community-based individuals from two UK centres between 1 April and 14 September 2020. Participants Individuals ≥18 years with persistent symptoms following recovery from acute SARS-CoV-2 infection and age-matched healthy controls. Intervention Assessment of symptoms by standardised questionnaires (EQ-5D-5L, Dyspnoea-12) and organ-specific metrics by biochemical assessment and quantitative MRI. Main outcome measures Severe post-COVID-19 syndrome defined as ongoing respiratory symptoms and/or moderate functional impairment in activities of daily living; single-organ and multiorgan impairment (heart, lungs, kidneys, liver, pancreas, spleen) by consensus definitions at baseline investigation. Results 201 individuals (mean age 45, range 21–71 years, 71% female, 88% white, 32% healthcare workers) completed the baseline assessment (median of 141 days following SARS-CoV-2 infection, IQR 110–162). The study population was at low risk of COVID-19 mortality (obesity 20%, hypertension 7%, type 2 diabetes 2%, heart disease 5%), with only 19% hospitalised with COVID-19. 42% of individuals had 10 or more symptoms and 60% had severe post-COVID-19 syndrome. Fatigue (98%), muscle aches (87%), breathlessness (88%) and headaches (83%) were most frequently reported. Mild organ impairment was present in the heart (26%), lungs (11%), kidneys (4%), liver (28%), pancreas (40%) and spleen (4%), with single-organ and multiorgan impairment in 70% and 29%, respectively. Hospitalisation was associated with older age (p=0.001), non-white ethnicity (p=0.016), increased liver volume (p Conclusions In individuals at low risk of COVID-19 mortality with ongoing symptoms, 70% have impairment in one or more organs 4 months after initial COVID-19 symptoms, with implications for healthcare and public health, which have assumed low risk in young people with no comorbidities. Trial registration number NCT04369807; Pre-results.

Idiopathic pulmonary fibrosis (IPF) is possibly the most rapidly progressive, chronic fibrosing condition in any organ. It is associated with a median survival of 3 years from diagnosis. The overall incidence of diagnosed IPF is increasing, in part as awareness of the diagnosis increases. Indeed, recent epidemiologic findings from the Respiratory Health of the Nation study in the United Kingdom indicate that IPF is twice as common as previously believed, with around 0.5 cases diagnosed per 1,000 of the UK population (1). Moreover, although it is considered a rare disease, IPF is strongly associated with ageing. In patients ≥70 years in age, its incidence is estimated between 1 and 4 per 1,000, and it is responsible for 1% of deaths in the United Kingdom (1–3). Clinical need remains under-served in terms of its diagnosis and effective treatment. Nevertheless, the direction of travel over recent years in both these aspects is encouraging. The evolution of guidelines and algorithms for multidisciplinary diagnosis of IPF (4) has been associated with increased consistency between specialist centres internationally (5). This appears to be accompanied by good identification of cases in which typically ‘IPF-like’ disease behaviour – progressive decline despite therapeutic intervention – is predicted, allowing proactive management planning. Within this ‘typical’ picture of disease progression, heterogeneity is increasingly recognized at both clinical and molecular levels, allowing the possibility of more personalized care in the future (6).

In line with the principles of ‘better communication and cooperation between community services and hospitals; between different teams working in the same buildings and between the NHS, local government and voluntary organisations’, the British Thoracic society (BTS) has promoted the

Protein turnover, orchestrated by a large array of proteases, protein complexes, and organelles consumes one-fifth of the human energy. In many diseases this homeostasis is lost resulting in loss of tissue function. One such group of diseases are the fibrotic disorders in which there is progressive fibroproliferation and extracellular matrix deposition. The causes of these diseases are sometimes identified, but often they are cryptic. In any case it is clear that there are shared pathways and processes leading to fibrosis in different tissues such as liver, lung, and kidney. There are also intense efforts to discover ways to inhibit the pathways that lead to fibrosis. Proteases of all classes are known to play roles in fibrosis. The matrix metalloproteases (MMPs) and their inhibitors (the tissue inhibitors of metalloproteinases, TIMPS) can degrade all extracellular matrix components and are thought to be central to pathogenesis. However, cysteine and serine proteases (including caspases, cathepsins, coagulation cascade proteases, and mast cell proteases) are also thought to regulate key processes and cell functions in fibrosis, including extracellular matrix gene expression, cell proliferation, cell apoptosis, epithelial mesenchymal transduction, and fibrocyte recruitment. The multiple pathways and range of proteases involved clearly provides challenges for therapy but it is not surprising that regulation of protease activity and the cell functions they control are being explored as potential targets to treat fibrotic disorders.

Respiratory disease accounts for a large part of acute medical presentations. Patients with acute respiratory problems are increasingly cared for on admissions units and can be discharged without respiratory physician input. Fortunately, the British Thoracic Society (BTS) and the National Institute for Health and Clinical Excellence (NICE) have produced excellent guidelines to assist in their management. Acute respiratory problems can be considered anatomically, separating into diseases of the airway, parenchyma, pleura and pulmonary vasculature, all of which can be complicated by respiratory failure.