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      Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome: a prospective, community-based study

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          Abstract

          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<0.0001), pancreatic inflammation (p<0.01), and fat accumulation in the liver (p<0.05) and pancreas (p<0.01). Severe post-COVID-19 syndrome was associated with radiological evidence of cardiac damage (myocarditis) (p<0.05).

          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.

          Related collections

          Most cited references41

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          OpenSAFELY: factors associated with COVID-19 death in 17 million patients

          COVID-19 has rapidly impacted on mortality worldwide. 1 There is unprecedented urgency to understand who is most at risk of severe outcomes, requiring new approaches for timely analysis of large datasets. Working on behalf of NHS England we created OpenSAFELY: a secure health analytics platform covering 40% of all patients in England, holding patient data within the existing data centre of a major primary care electronic health records vendor. Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19 related deaths. COVID-19 related death was associated with: being male (hazard ratio 1.59, 95%CI 1.53-1.65); older age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared to people with white ethnicity, black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48, 1.29-1.69 and 1.45, 1.32-1.58 respectively). We have quantified a range of clinical risk factors for COVID-19 related death in the largest cohort study conducted by any country to date. OpenSAFELY is rapidly adding further patients’ records; we will update and extend results regularly.
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            Persistent Symptoms in Patients After Acute COVID-19

            This case series describes COVID-19 symptoms persisting a mean of 60 days after onset among Italian patients previously discharged from COVID-19 hospitalization.
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              Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study

              Abstract Objective To characterise the clinical features of patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United Kingdom during the growth phase of the first wave of this outbreak who were enrolled in the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study, and to explore risk factors associated with mortality in hospital. Design Prospective observational cohort study with rapid data gathering and near real time analysis. Setting 208 acute care hospitals in England, Wales, and Scotland between 6 February and 19 April 2020. A case report form developed by ISARIC and WHO was used to collect clinical data. A minimal follow-up time of two weeks (to 3 May 2020) allowed most patients to complete their hospital admission. Participants 20 133 hospital inpatients with covid-19. Main outcome measures Admission to critical care (high dependency unit or intensive care unit) and mortality in hospital. Results The median age of patients admitted to hospital with covid-19, or with a diagnosis of covid-19 made in hospital, was 73 years (interquartile range 58-82, range 0-104). More men were admitted than women (men 60%, n=12 068; women 40%, n=8065). The median duration of symptoms before admission was 4 days (interquartile range 1-8). The commonest comorbidities were chronic cardiac disease (31%, 5469/17 702), uncomplicated diabetes (21%, 3650/17 599), non-asthmatic chronic pulmonary disease (18%, 3128/17 634), and chronic kidney disease (16%, 2830/17 506); 23% (4161/18 525) had no reported major comorbidity. Overall, 41% (8199/20 133) of patients were discharged alive, 26% (5165/20 133) died, and 34% (6769/20 133) continued to receive care at the reporting date. 17% (3001/18 183) required admission to high dependency or intensive care units; of these, 28% (826/3001) were discharged alive, 32% (958/3001) died, and 41% (1217/3001) continued to receive care at the reporting date. Of those receiving mechanical ventilation, 17% (276/1658) were discharged alive, 37% (618/1658) died, and 46% (764/1658) remained in hospital. Increasing age, male sex, and comorbidities including chronic cardiac disease, non-asthmatic chronic pulmonary disease, chronic kidney disease, liver disease and obesity were associated with higher mortality in hospital. Conclusions ISARIC WHO CCP-UK is a large prospective cohort study of patients in hospital with covid-19. The study continues to enrol at the time of this report. In study participants, mortality was high, independent risk factors were increasing age, male sex, and chronic comorbidity, including obesity. This study has shown the importance of pandemic preparedness and the need to maintain readiness to launch research studies in response to outbreaks. Study registration ISRCTN66726260.
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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2021
                30 March 2021
                30 March 2021
                : 11
                : 3
                : e048391
                Affiliations
                [1 ] Perspectum , Oxford, UK
                [2 ] departmentDepartment of Cardiology , Great Western Hospital Foundation NHS Trust , Swindon, UK
                [3 ] departmentDepartment of Cardiology , Oxford University Hospitals NHS Foundation Trust , Oxford, UK
                [4 ] Alliance Medical , Warwick, UK
                [5 ] departmentDepartment of Gastroenterology , Guy's and St Thomas' NHS Foundation Trust , London, UK
                [6 ] departmentInstitute for Liver and Digestive Health , University College London , London, UK
                [7 ] departmentInstitute of Cardiovascular and Metabolic Medicine , University of Liverpool , Liverpool, UK
                [8 ] departmentInstitute of Infection and Global Health , University of Liverpool , Liverpool, UK
                [9 ] departmentDepartment of Respiratory Research , Liverpool University Hospitals NHS Foundation Trust , Liverpool, UK
                [10 ] departmentDepartment of Respiratory Medicine , Hull and East Yorkshire Hospitals NHS Trust , Hull, UK
                [11 ] departmentInstitute of Clinical and Applied Health Research , University of Hull , Hull, UK
                [12 ] departmentInstitute of Population Health Sciences , University of Liverpool , Liverpool, UK
                [13 ] departmentDepartment of Oncology , University of Oxford , Oxford, UK
                [14 ] Long COVID SOS , Oxford, UK
                [15 ] UKDoctors#Longcovid , London, UK
                [16 ] departmentDepartment of Medicine , University College London Hospitals NHS Foundation Trust , London, UK
                [17 ] departmentInstitute of Health Informatics , University College London , London, UK
                [18 ] departmentDepartment of Cardiology , Barts Health NHS Trust , London, UK
                Author notes
                [Correspondence to ] Dr Amitava Banerjee; ami.banerjee@ 123456ucl.ac.uk

                RB and AB are joint senior authors.

                Author information
                http://orcid.org/0000-0001-8741-3411
                Article
                bmjopen-2020-048391
                10.1136/bmjopen-2020-048391
                8727683
                33785495
                609b17a6-71d0-4d1b-932a-4cfe983830f2
                © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:  https://creativecommons.org/licenses/by/4.0/.

                History
                : 26 December 2020
                : 25 February 2021
                : 11 March 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100006041, Innovate UK;
                Award ID: 104688
                Funded by: FundRef http://dx.doi.org/10.13039/100010675, H2020 Innovation In SMEs;
                Award ID: 719445
                Categories
                Health Services Research
                1506
                2474
                1704
                Original research
                Custom metadata
                unlocked

                Medicine
                covid-19,epidemiology,health policy,public health
                Medicine
                covid-19, epidemiology, health policy, public health

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