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Background The reduced renal function has prognostic significance in COVID-19 and it has been linked to mortality in the general population. Reduced renal function is prevalent in older age and thus we set out to better understand its effect on mortality. Methods Patient clinical and demographic data was taken from the COVID-19 in Older People (COPE) study during two periods (February–June 2020 and October 2020–March 2021, respectively). Kidney function on admission was measured using estimated glomerular filtration rate (eGFR). The primary outcomes were time to mortality and 28-day mortality. Secondary outcome was length of hospital stay. Data were analysed with multilevel Cox proportional hazards regression, and multilevel logistic regression and adjusted for individual patient clinical and demographic characteristics. Results One thousand eight hundred two patients (55.0% male; median [IQR] 80 [73–86] years) were included in the study. 28-day mortality was 42.3% (n = 742). 48% (n = 801) had evidence of renal impairment on admission. Using a time-to-event analysis, reduced renal function was associated with increased in-hospital mortality (compared to eGFR ≥ 60 [Stage 1&2]): eGFR 45–59 [Stage 3a] aHR = 1.26 (95%CI 1.02–1.55); eGFR 30–44 [Stage 3b] aHR = 1.41 (95%CI 1.14–1.73); eGFR 1–29 [Stage 4&5] aHR = 1.42 (95%CI 1.13–1.80). In the co-primary outcome of 28-day mortality, mortality was associated with: Stage 3a adjusted odds ratio (aOR) = 1.18 (95%CI 0.88–1.58), Stage 3b aOR = 1.40 (95%CI 1.03–1.89); and Stage 4&5 aOR = 1.65 (95%CI 1.16–2.35). Conclusion eGFR on admission is a good independent predictor of mortality in hospitalised older patients with COVID-19 population. We found evidence of a dose-response between reduced renal function and increased mortality.

IntroductionAs the population ages, frailty is becoming more common and understanding how frailty impacts on patient outcomes has become an integral part of clinical care. To date, there is no evidence available on the relationship between frailty and patient outcomes in pleural disease. In this study we explore the relationship between frailty and both malignant and non-malignant pleural disease using the modified frailty index (mFI).Methods and AnalysisOutpatients with pleural disease will be identified from a prospectively collected single-centre UK database and their data and notes retrospectively analysed. An mFI will be calculated for each patient and the correlation between their frailty index, final diagnosis and mortality analysed.DisseminationStudy findings will be disseminated by publication in an appropriate journal and presentations at Respiratory and/or Geriatric medicine meetings.

Background The objective of this study was to characterize frailty and resilience in people evaluated for Post-Acute COVID-19 Syndrome (PACS), in relation to quality of life (QoL) and Intrinsic Capacity (IC). Methods This cross-sectional, observational, study included consecutive people previously hospitalized for severe COVID-19 pneumonia attending Modena (Italy) PACS Clinic from July 2020 to April 2021. Four frailty-resilience phenotypes were built: “fit/resilient”, “fit/non-resilient”, “frail/resilient” and “frail/non-resilient”. Frailty and resilience were defined according to frailty phenotype and Connor Davidson resilience scale (CD-RISC-25) respectively. Study outcomes were: QoL assessed by means of Symptoms Short form health survey (SF-36) and health-related quality of life (EQ-5D-5L) and IC by means of a dedicated questionnaire. Their predictors including frailty-resilience phenotypes were explored in logistic regressions. Results 232 patients were evaluated, median age was 58.0 years. PACS was diagnosed in 173 (74.6%) patients. Scarce resilience was documented in 114 (49.1%) and frailty in 72 (31.0%) individuals. Table 1 shows demographic, anthropometric and clinical characteristics, comorbidities and patient-reported outcomes according to four frailty-resilience phenotypes. With regards to study outcomes, Figure 1 depicts in radar graphs, mean scores of each domain of SF-36 (1A), EQ-5D5L (1B) and IC (1C). Figures shows polygon areas for each frailty/resilience phenotypes. Progressive increase of mean scores of each domain are plotted in the vertices of polygons, from the lowest (near the center) in frail and non-resilient, to highest (towards periphery) in fit and resilient. Multivariate logistic analyses were used to identify predictors of the total scores of SF-36 (Figure 2A), EQ-5D5L (Figure 2B) and IC (Figure 2C). Conclusion Resilience is complementary to frailty in the identification of clinical phenotypes with different impact on wellness and QoL. Frailty and resilience should be evaluated in hospitalized COVID-19 patients to identify vulnerable individuals to prioritize urgent health interventions in people with PACS. Funding This study is supported by a Gilead Sciences Inc. unrestricted grant. Disclosures All Authors: No reported disclosures.

Background Older patients have a less pronounced immune response to infection, which may also influence infection biomarkers. There is currently insufficient data regarding clinical effects of procalcitonin (PCT) to guide antibiotic treatment in older patients. Objective and design We performed an individual patient data meta-analysis to investigate the association of age on effects of PCT-guided antibiotic stewardship regarding antibiotic use and outcome. Subjects and methods We had access to 9,421 individual infection patients from 28 randomized controlled trials comparing PCT-guided antibiotic therapy (intervention group) or standard care. We stratified patients according to age in four groups (85 years [n = 505]). The primary endpoint was the duration of antibiotic treatment and the secondary endpoints were 30-day mortality and length of stay. Results Compared to control patients, mean duration of antibiotic therapy in PCT-guided patients was significantly reduced by 24, 22, 26 and 24% in the four age groups corresponding to adjusted differences in antibiotic days of −1.99 (95% confidence interval [CI] −2.36 to −1.62), −1.98 (95% CI −2.94 to −1.02), −2.20 (95% CI −3.15 to −1.25) and − 2.10 (95% CI −3.29 to −0.91) with no differences among age groups. There was no increase in the risk for mortality in any of the age groups. Effects were similar in subgroups by infection type, blood culture result and clinical setting (P interaction >0.05). Conclusions This large individual patient data meta-analysis confirms that, similar to younger patients, PCT-guided antibiotic treatment in older patients is associated with significantly reduced antibiotic exposures and no increase in mortality.

Background C-reactive protein (CRP) is a non-specific acute phase reactant elevated in infection or inflammation. Higher levels indicate more severe infection and have been used as an indicator of COVID-19 disease severity. However, the evidence for CRP as a prognostic marker is yet to be determined. The aim of this study is to examine the CRP response in patients hospitalized with COVID-19 and to determine the utility of CRP on admission for predicting inpatient mortality. Methods Data were collected between 27 February and 10 June 2020, incorporating two cohorts: the COPE (COVID-19 in Older People) study of 1564 adult patients with a diagnosis of COVID-19 admitted to 11 hospital sites (test cohort) and a later validation cohort of 271 patients. Admission CRP was investigated, and finite mixture models were fit to assess the likely underlying distribution. Further, different prognostic thresholds of CRP were analysed in a time-to-mortality Cox regression to determine a cut-off. Bootstrapping was used to compare model performance [Harrell’s C statistic and Akaike information criterion (AIC)]. Results The test and validation cohort distribution of CRP was not affected by age, and mixture models indicated a bimodal distribution. A threshold cut-off of CRP ≥40 mg/L performed well to predict mortality (and performed similarly to treating CRP as a linear variable). Conclusions The distributional characteristics of CRP indicated an optimal cut-off of ≥40 mg/L was associated with mortality. This threshold may assist clinicians in using CRP as an early trigger for enhanced observation, treatment decisions and advanced care planning.

Background Effective shielding measures and virus mutations have progressively modified the disease between the waves, likewise healthcare systems have adapted to the outbreak. Our aim was to compare clinical outcomes for older people with COVID-19 in Wave 1 (W1) and Wave 2 (W2). Methods All data, including the Clinical Frailty Scale (CFS), were collected for COVID-19 consecutive patients, aged ≥65, from 13 hospitals, in W1 (February–June 2020) and W2 (October 2020–March 2021). The primary outcome was mortality (time to mortality and 28-day mortality). Data were analysed with multilevel Cox proportional hazards, linear and logistic regression models, adjusted for wave baseline demographic and clinical characteristics. Results Data from 611 people admitted in W2 were added to and compared with data collected during W1 (N = 1340). Patients admitted in W2 were of similar age, median (interquartile range), W2 = 79 (73–84); W1 = 80 (74–86); had a greater proportion of men (59.4% vs. 53.0%); had lower 28-day mortality (29.1% vs. 40.0%), compared to W1. For combined W1–W2 sample, W2 was independently associated with improved survival: time-to-mortality adjusted hazard ratio (aHR) = 0.78 [95% confidence interval (CI) 0.65–0.93], 28-day mortality adjusted odds ratio = 0.80 (95% CI 0.62–1.03). W2 was associated with increased length of hospital stay aHR = 0.69 (95% CI 0.59–0.81). Patients in W2 were less frail, CFS [adjusted mean difference (aMD) = −0.50, 95% CI −0.81, −0.18], as well as presented with lower C-reactive protein (aMD = −22.52, 95% CI −32.00, −13.04). Conclusions COVID-19 older adults in W2 were less likely to die than during W1. Patients presented to hospital during W2 were less frail and with lower disease severity and less likely to have renal decline.

Background\ud\udFrailty is associated with long-term physical deterioration after COVID-19. Mental health recovery has been less well investigated. Early studies have shown minimal effect from the virus, although studies have not focused on whether people living with frailty may have different psychiatric outcomes. We aimed to examine the effect of living with frailty on mental health outcomes one year after hospital with COVID-19.\udMethods\ud\udWe undertook a multicentre cross-sectional study of people admitted with COVID-19. We assessed quality of life (ICECAP-O and MRC), psychiatric symptoms including: generalised anxiety (GAD-7), depression (Patient Health Questionnaire-9), and trauma (Trauma Screening Questionnaire). Frailty was measured using the Clinical Frailty Scale (CFS). We used a multivariable mixed-effects logistic and linear regression to examine the adjusted odds ratio (aOR) and adjusted mean difference (aMD).\udResults\ud\udFrom eight hospitals 224 participants consented. Median follow-up time from admission 358 days (IQR 153–418), mean age 63.8 (SD = 13.7), 34.8% female (n = 78), and 43.7% living with frailty (n = 98 CFS 4–8). People living with frailty were significantly more likely to have symptoms of anxiety aOR = 5.72 (95% CI 1.71–19.13), depression aOR = 2.52 (95% CI 1.59–14.91), post-traumatic stress disorder aMD = 1.16 (95% CI 0.47, 1.85), and worse quality of life aMD = 1.06 (95% CI 0.76–1.36).\udLimitations\ud\udPatient-rated symptoms were captured rather than formal mental health diagnoses. CFS has not been validated in under 65-year-olds.\udConclusions\ud\udLiving with frailty is associated with significant psychiatric morbidity and reduced wellbeing one year after COVID-19 hospital admission. We recommend clinical follow-up after COVID-19 for people living with frailty should include a psychiatric assessment.

Background A proposal has recently been advanced to change the traditional definition of nonalcoholic fatty liver disease to metabolic-associated fatty liver disease (MAFLD), to reflect the cluster of metabolic abnormalities that may be more closely associated with cardiovascular risk. Long coronavirus disease 2019 (COVID-19) is a smoldering inflammatory condition, characterized by several symptom clusters. This study aims to determine the prevalence of MAFLD in patients with postacute COVID syndrome (PACS) and its association with other PACS-cluster phenotypes. Methods We included 235 patients observed at a single university outpatient clinic. The diagnosis of PACS was based on ≥1 cluster of symptoms: respiratory, neurocognitive, musculoskeletal, psychological, sensory, and dermatological. The outcome was prevalence of MAFLD detected by transient elastography during the first postdischarge follow-up outpatient visit. The prevalence of MAFLD at the time of hospital admission was calculated retrospectively using the hepatic steatosis index. Results Of 235 patients, 162 (69%) were men (median age 61). The prevalence of MAFLD was 55.3% at follow-up and 37.3% on admission (P Conclusions Metabolic-associated fatty liver disease was highly prevalent after hospital discharge and may represent a specific PACS-cluster phenotype, with potential long-term metabolic and cardiovascular health implications.

Objectives Patients with impaired kidney function have a significantly slower decrease of procalcitonin (PCT) levels during infection. Our aim was to study PCT-guided antibiotic stewardship and clinical outcomes in patients with impairments of kidney function as assessed by creatinine levels measured upon hospital admission. Methods We pooled and analyzed individual data from 15 randomized controlled trials who were randomly assigned to receive antibiotic therapy based on a PCT-algorithms or based on standard of care. We stratified patients on the initial glomerular filtration rate (GFR, ml/min/1.73 m2) in three groups (GFR >90 [chronic kidney disease; CKD 1], GFR 15–89 [CKD 2–4] and GFR Results Mean duration of antibiotic treatment was significantly shorter in PCT-guided (n=2,492) compared to control patients (n=2,510) (9.5–7.6 days; adjusted difference in days −2.01 [95% CI, −2.45 to −1.58]). CKD 5 patients had overall longer treatment durations, but a 2.5-day reduction in treatment duration was still found in patients receiving in PCT-guided care (11.3 vs. 8.6 days [95% CI −3.59 to −1.40]). There were 397 deaths in 2,492 PCT-group patients (15.9%) compared to 460 deaths in 2,510 control patients (18.3%) (adjusted odds ratio, 0.88 [95% CI 0.78 to 0.98)]. Effects of PCT-guidance on antibiotic treatment duration and mortality were similar in subgroups stratified by infection type and clinical setting (p interaction >0.05). Conclusions This individual patient data meta-analysis confirms that the use of PCT in patients with impaired kidney function, as assessed by admission creatinine levels, is associated with shorter antibiotic courses and lower mortality rates.

Background In response to the COVID-19 pandemic, many countries mandated staying at home to reduce transmission. This study examined the association between living arrangements (house occupancy numbers) and outcomes in COVID-19. Methods Study population was drawn from the COPE study, a multicentre cohort study. House occupancy was defined as: living alone; living with one other person; living with multiple other people; or living in a nursing/residential home. Outcomes were time from admission to mortality and discharge (Cox regression), and Day 28 mortality (logistic regression) analyses were adjusted for key comorbidities and covariates including admission: age, sex, smoking, heart failure, admission C-reactive protein (CRP), chronic obstructive pulmonary disease, estimated glomerular filtration rate, frailty and others. Results A total of 1584 patients were included from 13 hospitals across UK and Italy: 676 (42.7%) were female, 907 (57.3%) were male, median age was 74 years (range: 19–101). At 28 days, 502 (31.7%) had died. Median admission CRP was 67, 82, 79.5 and 83 mg/l for those living alone, with someone else, in a house of multiple occupancy and in a nursing/residential home, respectively. Compared to living alone, living with anyone was associated with increased mortality: within a couple [adjusted hazard ratios (aHR) = 1.39, 95% confidence intervals (CI) 1.09–1.77, P = 0.007]; living in a house of multiple occupancy (aHR = 1.67, 95% CI 1.17–2.38, P = 0.005); and living in a residential home (aHR = 1.36, 95% CI 1.03–1.80, P = 0.031). Conclusion For patients hospitalized with COVID-19, those living with one or more people had an increased association with mortality, they also exhibited higher CRP indicating increased disease severity suggesting they delayed seeking care.

Supplemental material, sj-pdf-1-taw-10.1177_2042098620985690 for Routine use of immunosuppressants is associated with mortality in hospitalised patients with COVID-19 by Phyo K. Myint, Ben Carter, Fenella Barlow-Pay, Roxanna Short, Alice G. Einarsson, Eilidh Bruce, Kathryn McCarthy, Alessia Verduri, Jemima Collins, James Hesford, Frances Rickard, Emma Mitchell, Mark Holloway, Aine McGovern, Arturo Vilches-Moraga, Philip Braude, Lyndsay Pearce, Michael Stechman, Angeline Price, Terence J. Quinn, Enrico Clini, Susan Moug and Jonathan Hewitt in Therapeutic Advances in Drug Safety

Background: \ud Hospital admissions for non-coronavirus disease 2019 (COVID-19) pathology have decreased significantly. It is believed that this may be due to public anxiety about acquiring COVID-19 infection in hospital and the subsequent risk of mortality.\ud \ud Aim: \ud To identify patients who acquire COVID-19 in hospital (nosocomial COVID-19 infection (NC)) and their risk of mortality compared to those with community-acquired COVID-19 (CAC) infection.\ud \ud Methods: \ud The COPE-Nosocomial Study was an observational cohort study. The primary outcome was the time to all-cause mortality (estimated with an adjusted hazard ratio (aHR)), and secondary outcomes were day 7 mortality and the time-to-discharge. A mixed-effects multivariable Cox's proportional hazards model was used, adjusted for demographics and comorbidities.\ud \ud Findings: \ud The study included 1564 patients from 10 hospital sites throughout the UK, and one in Italy, and collected outcomes on patients admitted up to April 28th, 2020. In all, 12.5% of COVID-19 infections were acquired in hospital; 425 (27.2%) patients with COVID died. The median survival time in NC patients was 14 days compared with 10 days in CAC patients. In the primary analysis, NC infection was associated with lower mortality rate (aHR: 0.71; 95% confidence interval (CI): 0.51–0.98). Secondary outcomes found no difference in day 7 mortality (adjusted odds ratio: 0.79; 95% CI: 0.47–1.31), but NC patients required longer time in hospital during convalescence (aHR: 0.49, 95% CI: 0.37–0.66).\ud \ud Conclusion: \ud The minority of COVID-19 cases were the result of NC transmission. No COVID-19 infection comes without risk, but patients with NC had a lower risk of mortality compared to CAC infection; however, caution should be taken when interpreting this finding.

BackgroundThe COVID-19 pandemic has placed significant pressure on health and social care. Survivors of COVID-19 may be left with substantial functional deficits requiring ongoing care. We aimed to determine whether pre-admission frailty was associated with increased care needs at discharge for patients admitted to hospital with COVID-19.MethodsPatients were included if aged over 18 years old and admitted to hospital with COVID-19 between 27 February and 10 June 2020. The Clinical Frailty Scale (CFS) was used to assess pre-admission frailty status. Admission and discharge care levels were recorded. Data were analysed using a mixed-effects logistic regression adjusted for age, sex, smoking status, comorbidities, and admission CRP as a marker of severity of disease.ResultsThirteen hospitals included patients: 1671 patients were screened, and 840 were excluded including, 521 patients who died before discharge (31.1%). Of the 831 patients who were discharged, the median age was 71 years (IQR, 58–81 years) and 369 (44.4%) were women. The median length of hospital stay was 12 days (IQR 6–24). Using the CFS, 438 (47.0%) were living with frailty (≥ CFS 5), and 193 (23.2%) required an increase in the level of care provided. Multivariable analysis showed that frailty was associated with an increase in care needs compared to patients without frailty (CFS 1–3). The adjusted odds ratios (aOR) were as follows: CFS 4, 1.99 (0.97–4.11); CFS 5, 3.77 (1.94–7.32); CFS 6, 4.04 (2.09–7.82); CFS 7, 2.16 (1.12–4.20); and CFS 8, 3.19 (1.06–9.56).ConclusionsAround a quarter of patients admitted with COVID-19 had increased care needs at discharge. Pre-admission frailty was strongly associated with the need for an increased level of care at discharge. Our results have implications for service planning and public health policy as well as a person's functional outcome, suggesting that frailty screening should be utilised for predictive modelling and early individualised discharge planning.