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BackgroundThere are currently no effective pharmacological or non-pharmacological interventions for Long-COVID. To identify potential therapeutic targets, we focussed on previously described four recovery clusters five months after hospital discharge, their underlying inflammatory profiles and relationship with clinical outcomes at one year. MethodsPHOSP-COVID is a prospective longitudinal cohort study, recruiting adults hospitalised with COVID-19 across the UK. Recovery was assessed using patient reported outcomes measures (PROMs), physical performance, and organ function at five-months and one-year after hospital discharge. Hierarchical logistic regression modelling was performed for patient-perceived recovery at one-year. Cluster analysis was performed using clustering large applications (CLARA) k-medoids approach using clinical outcomes at five-months. Inflammatory protein profiling from plasma at the five-month visit was performed. Findings2320 participants have been assessed at five months after discharge and 807 participants have completed both five-month and one-year visits. Of these, 35{middle dot}6% were female, mean age 58{middle dot}7 (SD 12{middle dot}5) years, and 27{middle dot}8% received invasive mechanical ventilation (IMV). The proportion of patients reporting full recovery was unchanged between five months 501/1965 (25{middle dot}5%) and one year 232/804 (28{middle dot}9%). Factors associated with being less likely to report full recovery at one year were: female sex OR 0{middle dot}68 (95% CI 0{middle dot}46-0{middle dot}99), obesity OR 0{middle dot}50 (95%CI 0{middle dot}34-0{middle dot}74) and IMV OR 0{middle dot}42 (95%CI 0{middle dot}23-0{middle dot}76). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate/cognitive, mild relating to the severity of physical, mental health and cognitive impairments at five months in a larger sample. There was elevation of inflammatory mediators of tissue damage and repair in both the very severe and the moderate/cognitive clusters compared to the mild cluster including interleukin-6 which was elevated in both comparisons. Overall, there was a substantial deficit in median (IQR) EQ5D-5L utility index from pre-COVID (retrospective assessment) 0{middle dot}88 (0{middle dot}74-1{middle dot}00), five months 0{middle dot}74 (0{middle dot}60-0{middle dot}88) to one year: 0{middle dot}74 (0{middle dot}59-0{middle dot}88), with minimal improvements across all outcome measures at one-year after discharge in the whole cohort and within each of the four clusters. InterpretationThe sequelae of a hospital admission with COVID-19 remain substantial one year after discharge across a range of health domains with the minority in our cohort feeling fully recovered. Patient perceived health-related quality of life remains reduced at one year compared to pre-hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials. FundingUKRI & NIHR Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe systematically searched PubMed and Embase databases for large studies reporting one-year follow-up data for hospitalised COVID-19 patients published between January 1, 2021 and November 7, 2021, without language restrictions. Search terms related to COVID-19, hospitalisation and long-term follow-up were used. A large prospective cohort study from Wuhan, China (n = 1276) showed that 49% of patients reported at least one persistent symptom during a follow-up clinic visit at 12 months post COVID-19; no significant improvement in exercise capacity was observed between six- and 12-month visits. Another two large cohort studies in China (n = 2433) and Spain (n = 1950) with one-year follow-up data from telephone interviews showed that 45% and 81% of patients reported at least one residual COVID-19 symptom, respectively. However, no previous studies have compared the trajectories of COVID-19 recovery in patients classified by different clinical phenotypes, and there are no large studies investigating the relationship between systemic inflammation and ongoing health impairments post COVID-19. Added value of this studyIn a diverse population of adults post-hospital admission with COVID-19, our large UK prospective multi-centre study reports several novel findings: the minority felt fully recovered at one year with minimal recovery from five months across any health domain; female sex and obesity are associated with being less likely to feel fully recovered at one year; several inflammatory mediators were increased in individuals with the most severe physical, mental health, and cognitive impairments compared to individuals with milder ongoing impairments. Implications of all the available evidenceBoth pharmacological and non-pharmacological interventions are urgently needed to improve the ongoing burden following hospitalisation for COVID-19 both for individuals and healthcare systems; our findings support the use of a precision medicine approach with potential treatable traits of systemic inflammation and obesity.
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BackgroundThe impact of COVID-19 on physical and mental health, and employment following hospitalisation is poorly understood. MethodsPHOSP-COVID is a multi-centre, UK, observational study of adults discharged from hospital with a clinical diagnosis of COVID-19 involving an assessment between two- and seven-months later including detailed symptom, physiological and biochemical testing. Multivariable logistic regression was performed for patient-perceived recovery with age, sex, ethnicity, body mass index (BMI), co-morbidities, and severity of acute illness as co-variates. Cluster analysis was performed using outcomes for breathlessness, fatigue, mental health, cognition and physical function. FindingsWe report findings of 1077 patients discharged in 2020, from the assessment undertaken a median 5 [IQR4 to 6] months later: 36% female, mean age 58 [SD 13] years, 69% white ethnicity, 27% mechanical ventilation, and 50% had at least two co-morbidities. At follow-up only 29% felt fully recovered, 20% had a new disability, and 19% experienced a health-related change in occupation. Factors associated with failure to recover were female, middle-age, white ethnicity, two or more co-morbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial and weakly related to acute severity. Four clusters were identified with different severities of mental and physical health impairment: 1) Very severe (17%), 2) Severe (21%), 3) Moderate with cognitive impairment (17%), 4) Mild (46%), with 3%, 7%, 36% and 43% feeling fully recovered, respectively. Persistent systemic inflammation determined by C-reactive protein was related to cluster severity, but not acute illness severity. InterpretationWe identified factors related to recovery from a hospital admission with COVID-19 and four different phenotypes relating to the severity of physical, mental, and cognitive health five months later. The implications for clinical care include the potential to stratify care and the need for a pro-active approach with wide-access to COVID-19 holistic clinical services. Funding: UKRI and NIHR
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ObjectivesTo define the burden of nosocomial (hospital-acquired) novel pandemic coronavirus (covid-19) infection among adults hospitalised across Wales. DesignRetrospective observational study of adult patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection between 1st March - 1st July 2020 with a recorded hospital admission within the subsequent 31 days. Outcomes were collected up to 20th November using a standardised online data collection tool. SettingService evaluation performed across 18 secondary or tertiary care hospitals. Participants4112 admissions with a positive SARS-CoV-2 PCR result between 1st March to 1st July 2020 were screened. Anonymised data from 2518 participants were returned, representing over 60% of adults hospitalised across the nation of Wales. Main outcome measuresThe prevalence and outcomes (death, discharge) for nosocomial covid-19, assessed across of a range of possible case definitions. ResultsInpatient mortality rates for nosocomial covid-19 ranged from 38% to 42% and remained consistently higher than participants with community-acquired infection (31% to 35%) across a range of case definitions. Participants with nosocomial-acquired infection were an older, frailer, and multi-morbid population than those with community-acquired infection. Based on the Public Health Wales case definition, 50% of participants had been admitted for 30 days prior to diagnostic testing. ConclusionsThis represents the largest assessment of clinical outcomes for patients with nosocomial covid-19 in the UK to date. These findings suggest that inpatient mortality rates from nosocomial-infection are likely higher than previously reported, emphasizing the importance of infection control measures, and supports prioritisation of vaccination for covid-19 negative admissions and trials of post-exposure prophylaxis in inpatient cohorts. Trial registrationThis project was approved and sponsored by the Welsh Government, as part of a national audit and quality improvement scheme for patients hospitalised covid-19 across Wales. Key MessagesO_ST_ABSWhat is already known on this topicC_ST_ABSWe searched PubMed and ISI Web of Science up until 31-December-2020 for studies reporting on patient outcomes following hospital-acquired infection due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We identified a range of case-definitions for hospital-acquired infection, based on timing of diagnostic testing 5 to 15 days following admission. The largest and only multi-centre study concluded individuals with nosocomial infection are at a lower risk of death from SARS-CoV-2 than those infected in the community, however, was performed early in the pandemic and utilised a conservative definition of nosocomial infection. What this study addsOur multi-centre observational study represents the largest assessment of clinical outcomes for patients with nosocomial covid-19 in the UK to date, and suggests the burden of nosocomial SARS-CoV-2 infection has been underestimated. Nosocomial-infection occurred in older, frailer, and multi-morbid individuals, and was consistently associated with greater inpatient mortality than amongst those who were infected in the community across a spectrum of case-definitions. Our findings support implementation of enhanced infection control measures to reduce this burden during future waves, especially given the recent emergence of novel viral variants with enhanced transmissibility. Furthermore, roughly half of the patients meeting the Public Health Wales definition of definite nosocomial SARS-CoV-2 infection had been admitted for 30 days prior to diagnosis, highlighting a potential window of opportunity for inpatient pre-exposure and/or post-exposure prophylaxis.
