Long COVID and cardiovascular disease: a prospective cohort study.

BACKGROUND: Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known. OBJECTIVES: To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors. METHODS: In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health. RESULTS: From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86). CONCLUSION: Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need. TRAIL REGISTRATION NUMBER: ISRCTN10980107.

The Rationale, Evidence, and Adaptations to Pulmonary Rehabilitation for Chronic Respiratory Diseases Other Than COPD.

Over the last 3 decades, pulmonary rehabilitation (PR) has become an integral part of the management of COPD. Many other chronic respiratory diseases have similar systemic manifestations including skeletal muscle impairment, commonly through deconditioning, and may benefit from PR. However, whereas many programs may accept patients with other respiratory diseases, the program may need several adaptations to optimally manage patients. This article uses the examples of interstitial lung disease including idiopathic pulmonary fibrosis, bronchiectasis, pulmonary hypertension, post lung transplantation, and post-COVID condition to highlight exemplar clinical problems. In addition, the rationale and latest evidence for PR are described alongside the adaptations to the program, including education needs of the delivery team and close integrated care with the wider clinical team. Finally, future directions for clinical care and research are discussed.

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease.

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.

Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (PERFORM): protocol for a randomised feasibility trial.

INTRODUCTION: Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (PERFORM) is a research programme that seeks to develop and evaluate a comprehensive exercise-based rehabilitation intervention designed for people with multimorbidity, the presence of multiple long-term conditions (MLTCs). This paper describes the protocol for a randomised trial to assess the feasibility and acceptability of the PERFORM intervention, study design and processes. METHODS AND ANALYSIS: A multicentre, parallel two-group randomised trial with individual 2:1 allocation to the PERFORM exercise-based intervention plus usual care (intervention) or usual care alone (control). The primary outcome of this feasibility trial will be to assess whether prespecified progression criteria (recruitment, retention, intervention adherence) are met to progress to the full randomised trial. The trial will be conducted across three UK sites and 60 people with MLTCs, defined as two or more LTCs, with at least one having evidence of the beneficial effect of exercise. The PERFORM intervention comprises an 8-week (twice a week for 6 weeks and once a week for 2 weeks) supervised rehabilitation programme of personalised exercise training and self-management education delivered by trained healthcare professionals followed by two maintenance sessions. Trial participants will be recruited over a 4.5-month period, and outcomes assessed at baseline (prerandomisation) and 3 months postrandomisation and include health-related quality of life, psychological well-being, symptom burden, frailty, exercise capacity, physical activity, sleep, cognition and serious adverse events. A mixed-methods process evaluation will assess acceptability, feasibility and fidelity of intervention delivery and feasibility of trial processes. An economic evaluation will assess the feasibility of data collection and estimate the costs of the PERFORM intervention. ETHICS AND DISSEMINATION: The trial has been given favourable opinion by the West Midlands, Edgbaston Research Ethics Service (Ref: 23/WM/0057). Participants will be asked to give full, written consent to take part by trained researchers. Findings will be disseminated via journals, presentations and targeted communications to clinicians, commissioners, service users and patients and the public. TRIAL REGISTRATION NUMBER: ISRCTN68786622. PROTOCOL VERSION: 2.0 (16 May 2023).

Accelarated immune ageing is associated with COVID-19 disease severity.

BACKGROUND: The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. RESULTS: We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3-5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28-ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ([Formula: see text] = 0.174, p = 0.043), with a major influence being disease severity ([Formula: see text] = 0.188, p = 0.01). CONCLUSIONS: Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease.

Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury.

A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury.

Plasma steroid concentrations reflect acute disease severity and normalise during recovery in people hospitalised with COVID-19.

OBJECTIVE: Endocrine systems are disrupted in acute illness, and symptoms reported following coronavirus disease 2019 (COVID-19) are similar to those found with clinical hormone deficiencies. We hypothesised that people with severe acute COVID-19 and with post-COVID symptoms have glucocorticoid and sex hormone deficiencies. DESIGN/PATIENTS: Samples were obtained for analysis from two UK multicentre cohorts during hospitalisation with COVID-19 (International Severe Acute Respiratory Infection Consortium/World Health Organisation [WHO] Clinical Characterization Protocol for Severe Emerging Infections in the UK study), and at follow-up 5 months after hospitalisation (Post-hospitalisation COVID-19 study). MEASUREMENTS: Plasma steroids were quantified by liquid chromatography-mass spectrometry. Steroid concentrations were compared against disease severity (WHO ordinal scale) and validated symptom scores. Data are presented as geometric mean (SD). RESULTS: In the acute cohort (n = 239, 66.5% male), plasma cortisol concentration increased with disease severity (cortisol 753.3 [1.6] vs. 429.2 [1.7] nmol/L in fatal vs. least severe, p < .001). In males, testosterone concentrations decreased with severity (testosterone 1.2 [2.2] vs. 6.9 [1.9] nmol/L in fatal vs. least severe, p < .001). In the follow-up cohort (n = 198, 62.1% male, 68.9% ongoing symptoms, 165 [121-192] days postdischarge), plasma cortisol concentrations (275.6 [1.5] nmol/L) did not differ with in-hospital severity, perception of recovery, or patient-reported symptoms. Male testosterone concentrations (12.6 [1.5] nmol/L) were not related to in-hospital severity, perception of recovery or symptom scores. CONCLUSIONS: Circulating glucocorticoids in patients hospitalised with COVID-19 reflect acute illness, with a marked rise in cortisol and fall in male testosterone. These findings are not observed 5 months from discharge. The lack of association between hormone concentrations and common post-COVID symptoms suggests steroid insufficiency does not play a causal role in this condition.

Prognostication of co-morbidity clusters on hospitalisation and mortality in advanced COPD.

RATIONALE: As the prevalence of multimorbidity increases, understanding the impact of isolated comorbidities in people COPD becomes increasingly challenging. A simplified model of common comorbidity patterns may improve outcome prediction and allow targeted therapy. OBJECTIVES: To assess whether comorbidity phenotypes derived from routinely collected clinical data in people with COPD show differences in risk of hospitalisation and mortality. METHODS: Twelve clinical measures related to common comorbidities were collected during annual reviews for people with advanced COPD and k-means cluster analysis performed. Cox proportional hazards with adjustment for covariates was used to determine hospitalisation and mortality risk between clusters. MEASUREMENTS AND MAIN RESULTS: In 203 participants (age 66 ± 9 years, 60 % male, FEV1%predicted 31 ± 10 %) no comorbidity in isolation was predictive of worse admission or mortality risk. Four clusters were described: cluster A (cardiometabolic and anaemia), cluster B (malnourished and low mood), cluster C (obese, metabolic and mood disturbance) and cluster D (less comorbid). FEV1%predicted did not significantly differ between clusters. Mortality risk was higher in cluster A (HR 3.73 [95%CI 1.09-12.82] p = 0.036) and B (HR 3.91 [95%CI 1.17-13.14] p = 0.027) compared to cluster D. Time to admission was highest in cluster A (HR 2.01 [95%CI 1.11-3.63] p = 0.020). Cluster C was not associated with increased risk of mortality or hospitalisation. CONCLUSIONS: Despite presence of advanced COPD, we report striking differences in prognosis for both mortality and hospital admissions for different co-morbidity phenotypes. Objectively assessing the multi-system nature of COPD could lead to improved prognostication and targeted therapy for patients.

Effect of aerobic exercise training on pulse wave velocity in adults with and without long-term conditions: a systematic review and meta-analysis.

RATIONALE: There is conflicting evidence whether aerobic exercise training (AET) reduces pulse wave velocity (PWV) in adults with and without long-term conditions (LTCs). OBJECTIVE: To explore whether PWV improves with AET in adults with and without LTC, to quantify the magnitude of any effect and understand the influence of the exercise prescription. DATA SOURCES: CENTRAL, MEDLINE and EMBASE were among the databases searched. ELIGIBILITY CRITERIA: We included studies with a PWV measurement before and after supervised AET of at least 3 weeks duration. Exclusion criteria included resistance exercise and alternative measures of arterial stiffness. DESIGN: Controlled trials were included in a random effects meta-analysis to explore the effect of AET on PWV. Uncontrolled studies were included in a secondary meta-analysis and meta-regression exploring the effect of patient and programme factors on change in PWV. The relevant risk of bias tool was used for each study design. RESULTS: 79 studies (n=3729) were included: 35 controlled studies (21 randomised control trials (RCT) (n=1240) and 12 non-RCT (n=463)) and 44 uncontrolled (n=2026). In the controlled meta- analysis, PWV was significantly reduced following AET (mean (SD) 11 (7) weeks) in adults with and without LTC (mean difference -0.63; 95% CI -0.82 to -0.44; p<0.0001). PWV was similarly reduced between adults with and without LTC (p<0.001). Age, but not specific programme factors, was inversely associated with a reduction in PWV -0.010 (-0.020 to -0.010) m/s, p<0.001. DISCUSSION: Short-term AET similarly reduces PWV in adults with and without LTC. Whether this effect is sustained and the clinical implications require further investigation.

Impact of COVID-19 on immunocompromised populations during the Omicron era: insights from the observational population-based INFORM study.

Background: Immunocompromised individuals are not optimally protected by COVID-19 vaccines and potentially require additional preventive interventions to mitigate the risk of severe COVID-19. We aimed to characterise and describe the risk of severe COVID-19 across immunocompromised groups as the pandemic began to transition to an endemic phase. Methods: COVID-19-related hospitalisations, intensive care unit (ICU) admissions, and deaths (01/01/2022-31/12/2022) were compared among different groups of immunocompromised individuals vs the general population, using a retrospective cohort design and electronic health data from a random 25% sample of the English population aged ≥12 years (Registration number: ISRCTN53375662). Findings: Overall, immunocompromised individuals accounted for 3.9% of the study population, but 22% (4585/20,910) of COVID-19 hospitalisations, 28% (125/440) of COVID-19 ICU admissions, and 24% (1145/4810) of COVID-19 deaths in 2022. Restricting to those vaccinated with ≥3 doses of COVID-19 vaccine (∼84% of immunocompromised and 51% of the general population), all immunocompromised groups remained at increased risk of severe COVID-19 outcomes, with adjusted incidence rate ratios (aIRR) for hospitalisation ranging from 1.3 to 13.1. At highest risk for COVID-19 hospitalisation were individuals with: solid organ transplant (aIRR 13.1, 95% confidence interval [95% CI] 11.2-15.3), moderate to severe primary immunodeficiency (aIRR 9.7, 95% CI 6.3-14.9), stem cell transplant (aIRR 11.0, 95% CI 6.8-17.6), and recent treatment for haematological malignancy (aIRR 10.6, 95% CI 9.5-11.9). Results were similar for COVID-19 ICU admissions and deaths. Interpretation: Immunocompromised individuals continue to be impacted disproportionately by COVID-19 and have an urgent need for additional preventive measures beyond current vaccination programmes. These data can help determine the immunocompromised groups for which targeted prevention strategies may have the highest impact. Funding: This study was funded by AstraZeneca UK.

Balancing the value and risk of exercise-based therapy post-COVID-19: a narrative review.

Coronavirus disease 2019 (COVID-19) can lead to ongoing symptoms such as breathlessness, fatigue and muscle pain, which can have a substantial impact on an individual. Exercise-based rehabilitation programmes have proven beneficial in many long-term conditions that share similar symptoms. These programmes have favourably influenced breathlessness, fatigue and pain, while also increasing functional capacity. Exercise-based rehabilitation may benefit those with ongoing symptoms following COVID-19. However, some precautions may be necessary prior to embarking on an exercise programme. Areas of concern include ongoing complex lung pathologies, such as fibrosis, cardiovascular abnormalities and fatigue, and concerns regarding post-exertional symptom exacerbation. This article addresses these concerns and proposes that an individually prescribed, symptom-titrated exercise-based intervention may be of value to individuals following infection with severe acute respiratory syndrome coronavirus 2.

Spirometry services in England post-pandemic and the potential role of AI support software: a qualitative study of challenges and opportunities.

BACKGROUND: Spirometry services to diagnose and monitor lung disease in primary care were identified as a priority in the NHS Long Term Plan, and are restarting post-COVID-19 pandemic in England; however, evidence regarding best practice is limited. AIM: To explore perspectives on spirometry provision in primary care, and the potential for artificial intelligence (AI) decision support software to aid quality and interpretation. DESIGN AND SETTING: Semi-structured interviews with stakeholders in spirometry services across England. METHOD: Participants were recruited by snowball sampling. Interviews explored the pre- pandemic delivery of spirometry, restarting of services, and perceptions of the role of AI. Transcripts were analysed thematically. RESULTS: In total, 28 participants (mean years' clinical experience = 21.6 [standard deviation 9.4, range 3-40]) were interviewed between April and June 2022. Participants included clinicians (n = 25) and commissioners (n = 3); eight held regional and/or national respiratory network advisory roles. Four themes were identified: 1) historical challenges in provision of spirometry services; 2) inequity in post- pandemic spirometry provision and challenges to restarting spirometry in primary care; 3) future delivery closer to patients' homes by appropriately trained staff; and 4) the potential for AI to have supportive roles in spirometry. CONCLUSION: Stakeholders highlighted historic challenges and the damaging effects of the pandemic contributing to inequity in provision of spirometry, which must be addressed. Overall, stakeholders were positive about the potential of AI to support clinicians in quality assessment and interpretation of spirometry. However, it was evident that validation of the software must be sufficiently robust for clinicians and healthcare commissioners to have trust in the process.

Cardiac rehabilitation for heart failure and atrial fibrillation: a propensity- matched study.

BACKGROUND: Atrial fibrillation (AF) is common in individuals with heart failure (HF). Individuals with HF and AF may have a reduced functional capacity and quality of life (QoL) which leads to hospital admission and burden on clinical services. Evidence supported the effect of exercise training in individuals with HF. However, there is no existing data on the effectiveness of comprehensive cardiac rehabilitation (CR) in individuals with coexisting HF and AF. AIM: To explore the effect of CR in individuals with HF and AF compared with those with HF and no-coexisting AF. METHODS: Using CR database, individuals with HF and AF were identified and propensity matched to those with no coexisting AF. The change in incremental shuttle walking test, Heart Disease Quality of Life questionnaire, Hospital Anxiety and Depression Scores were compared between groups pre-CR and post-CR. RESULTS: 149 individuals were propensity matched from each group. The mean±SD age of the matched sample was 73.4±8 years, body mass index 29±5.5 kg/m2, left ventricular ejection fraction 35.2±9.8% and 56% were male.A statistically significant improvements in exercise capacity, heart disease QoL, anxiety and depression scores were observed within each group. There were no significant differences between groups for any of these outcome measures. CONCLUSIONS: Individuals with HF and AF gain a similar improvement in exercise capacity and health related QoL outcomes as individuals with no coexisting AF following CR. The presence of AF did not compromise the effectiveness of CR.

A typology of healthcare pathways after hospital discharge for adults with COVID-19: the evolution of UK services during pandemic conditions.

Introduction: Over half of post-COVID-hospitalisation adults have persistent symptoms 2 years after discharge, providing a challenge for individuals and healthcare systems. We therefore aimed to describe a typology of UK healthcare pathways post-hospital discharge as a first step towards understanding clinical effectiveness and cost-effectiveness of different healthcare pathways. Methods: In 2021, we surveyed hospital sites taking part in the UK Post-hospital COVID-19 (PHOSP-COVID) study. The online survey explored the availability of proactive follow-up, patient selection, involvement of multidisciplinary teams, investigations, assessment and access to mental health and rehabilitation interventions. The typology was defined by a three-stage process: 1) using the survey results to develop a bespoke algorithm to inform a draft classification, 2) a stakeholder event for refinement and 3) finalisation between the Project Advisory Group and research team. The bespoke algorithm was used to map each site onto the classification with further mapping by level of mental health and rehabilitation provision. Results: 70% of hospital sites (45 out of 64) responded to the survey. 82% (37 out of 45) reported delivering a follow-up service after hospital discharge during the first few months of the pandemic. Only 13 out of 37 services (35%) were delivered by permanent staff. The final typology of five categories included no proactive follow-up, and a matrix of four groups based on patient selection (prespecified subgroup/all patients) and complexity of assessment (low/high). The complexity of assessment, rehabilitation and mental health interventions was variable within sites. Discussion: We describe the first typology of post-hospitalisation COVID-19 healthcare pathways to enable modelling of clinical effectiveness and cost-effectiveness to inform future policy. Our results highlight the heterogeneity and vulnerability of healthcare services after COVID-19 hospitalisation.

ERS International Congress 2022: highlights from the Respiratory Clinical Care and Physiology Assembly.

It is a challenge to keep abreast of all the clinical and scientific advances in the field of respiratory medicine. This article contains an overview of the laboratory-based science, clinical trials and qualitative research that were presented during the 2022 European Respiratory Society International Congress within the sessions from the five groups of Assembly 1 (Respiratory Clinical Care and Physiology). Selected presentations are summarised from a wide range of topics: clinical problems, rehabilitation and chronic care, general practice and primary care, mobile/electronic health (m-health/e-health), clinical respiratory physiology, exercise and functional imaging.

Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization.

Post-COVID cognitive deficits, including 'brain fog', are clinically complex, with both objective and subjective components. They are common and debilitating, and can affect the ability to work, yet their biological underpinnings remain unknown. In this prospective cohort study of 1,837 adults hospitalized with COVID-19, we identified two distinct biomarker profiles measured during the acute admission, which predict cognitive outcomes 6 and 12 months after COVID-19. A first profile links elevated fibrinogen relative to C-reactive protein with both objective and subjective cognitive deficits. A second profile links elevated D-dimer relative to C-reactive protein with subjective cognitive deficits and occupational impact. This second profile was mediated by fatigue and shortness of breath. Neither profile was significantly mediated by depression or anxiety. Results were robust across secondary analyses. They were replicated, and their specificity to COVID-19 tested, in a large-scale electronic health records dataset. These findings provide insights into the heterogeneous biology of post-COVID cognitive deficits.

Responsive and resilient healthcare? 'Moments of Resilience' in post-hospitalisation services for COVID-19.

BACKGROUND: COVID-19 caused disruption to healthcare services globally, resulting in high numbers of hospital admissions and with those discharged often requiring ongoing support. Within the UK, post-discharge services typically developed organically and were shaped over time by local need, funding, and government guidance. Drawing on the Moments of Resilience framework, we explore the development of follow-up services for hospitalised patients by considering the links between resilience at different system levels over time. This study contributes to the resilient healthcare literature by providing empirical evidence of how diverse stakeholders developed and adapted services for patients following hospitalisation with COVID-19 and how action taken at one system level influenced another. METHODS: Qualitative research comprising comparative case studies based on interviews. Across three purposively selected case studies (two in England, one in Wales) a total of 33 semi-structured interviews were conducted with clinical staff, managers and commissioners who had been involved in developing and/or implementing post-hospitalisation follow-up services. The interviews were audio-recorded and professionally transcribed. Analysis was conducted with the aid of NVivo 12. RESULTS: Case studies demonstrated three distinct examples of how healthcare organisations developed and adapted their post-discharge care provision for patients, post-hospitalisation with COVID-19. Initially, the moral distress of witnessing the impact of COVID-19 on patients who were being discharged coupled with local demand gave clinical staff the impetus to take action. Clinical staff and managers worked closely to plan and deliver organisations' responses. Funding availability and other contextual factors influenced situated and immediate responses and structural adaptations to the post-hospitalisation services. As the pandemic evolved, NHS England and the Welsh government provided funding and guidance for systemic adaptations to post-COVID assessment clinics. Over time, adaptations made at the situated, structural, and systemic levels influenced the resilience and sustainability of services. CONCLUSIONS: This paper addresses understudied, yet inherently important, aspects of resilience in healthcare by exploring when and where resilience occurs across the healthcare system and how action taken at one system level influenced another. Comparison across the case studies showed that organisations responded in similar and different ways and on varying timescales to a disruption and national level strategies.