Different neurological manifestations of COVID-19 in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicenter observational study using the International Severe Acute Respiratory and emerging Infection Consortium cohort across 1507 sites worldwide from January/30th/2020 to May/25th/2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161,239 patients (158,267 adults; 2,972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%), and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%), and central nervous system (CNS) infection (0.2%). Each occurred more frequently in ICU than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU vs. non-ICU (7.1% vs. 2.3%, P < .001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease, and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure, and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.

Background There is limited evidence concerning the effectiveness of enhanced recovery programmes in hip and knee replacement surgery, particularly when applied nationwide across a health-care system. Objectives To determine the effect of hospital organisation, surgical factors and the enhanced recovery after surgery pathway on patient outcomes and NHS costs of hip and knee replacement. Design (1) Statistical analysis of national linked data to explore geographical variations in patient outcomes of surgery. (2) A natural experimental study to determine clinical effectiveness of enhanced recovery after surgery. (3) A qualitative study to identify barriers to, and facilitators of, change. (4) Health economics analysis to establish NHS costs and cost-effectiveness. Setting Data from the National Joint Registry, linked to English Hospital Episode Statistics and patient-reported outcome measures in both the geographical variation and natural experiment studies, together with the economic evaluation. The ethnographic study took place in four hospitals in a region of England. Participants Qualitative study – 38 health professionals working in hip and knee replacement services in secondary care and 37 patients receiving hip or knee replacement. Interventions Natural experiment – implementation of enhanced recovery after surgery at each hospital between 2009 and 2011. Enhanced recovery after surgery is a complex intervention focusing on several areas of patients’ care pathways through surgery: preoperatively (patient is in best possible condition for surgery), perioperatively (patient has best possible management during and after operation) and postoperatively (patient experiences best rehabilitation). Main outcome measures Patient-reported pain and function (Oxford Hip Score/Oxford Knee Score); 6-month complications; length of stay; bed-day costs; and revision surgery within 5 years. Results Geographical study – there are potentially unwarranted variations in patient outcomes of hip and knee replacement surgery. This variation cannot be explained by differences in patients, case mix, surgical or hospital organisational factors. Qualitative – successful implementation depends on empowering patients to work towards their recovery, providing post-discharge support and promoting successful multidisciplinary team working. Care processes were negotiated between patients and health-care professionals. ‘Good care’ remains an aspiration, particularly in the post-discharge period. Natural experiment – length of stay has declined substantially, pain and function have improved, revision rates are in decline and complication rates remain stable. The introduction of a national enhanced recovery after surgery programme maintained improvement, but did not alter the rate of change already under way. Health economics – costs are high in the year of joint replacement and remain higher in the subsequent year after surgery. There is a strong economic incentive to identify ways of reducing revisions and complications following joint replacement. Published cost-effectiveness evidence supports enhanced recovery pathways as a whole. Limitations Short duration of follow-up data prior to enhanced recovery after surgery implementation and missing data, particularly for hospital organisation factors. Conclusion No evidence was found to show that enhanced recovery after surgery had a substantial impact on longer-term downwards trends in costs and length of stay. Trends of improving outcomes were seen across all age groups, in those with and without comorbidity, and had begun prior to the formal enhanced recovery after surgery roll-out. Reductions in length of stay have been achieved without adversely affecting patient outcomes, yet, substantial variation remains in outcomes between hospital trusts. Future work There is still work to be done to reduce and understand unwarranted variations in outcome between individual hospitals. Study registration This study is registered as PROSPERO CRD42017059473. Funding This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 8, No. 4. See the NIHR Journals Library website for further project information.

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.

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Background We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. Methods The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). Results Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. Conclusions Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death.