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      Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19

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      , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ISARIC Clinical Characterisation Group
      International Journal of Epidemiology
      Oxford University Press
      COVID-19, SARS-CoV-2, cohort study, risk of death, co-morbidities, symptoms, treatments

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          Abstract

          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.

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          Most cited references32

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          Male sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission

          Anecdotal evidence suggests that Coronavirus disease 2019 (COVID-19), caused by the coronavirus SARS-CoV-2, exhibits differences in morbidity and mortality between sexes. Here, we present a meta-analysis of 3,111,714 reported global cases to demonstrate that, whilst there is no difference in the proportion of males and females with confirmed COVID-19, male patients have almost three times the odds of requiring intensive treatment unit (ITU) admission (OR = 2.84; 95% CI = 2.06, 3.92) and higher odds of death (OR = 1.39; 95% CI = 1.31, 1.47) compared to females. With few exceptions, the sex bias observed in COVID-19 is a worldwide phenomenon. An appreciation of how sex is influencing COVID-19 outcomes will have important implications for clinical management and mitigation strategies for this disease.
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            Assessing the age specificity of infection fatality rates for COVID-19: systematic review, meta-analysis, and public policy implications

            Determine age-specific infection fatality rates for COVID-19 to inform public health policies and communications that help protect vulnerable age groups. Studies of COVID-19 prevalence were collected by conducting an online search of published articles, preprints, and government reports that were publicly disseminated prior to 18 September 2020. The systematic review encompassed 113 studies, of which 27 studies (covering 34 geographical locations) satisfied the inclusion criteria and were included in the meta-analysis. Age-specific IFRs were computed using the prevalence data in conjunction with reported fatalities 4 weeks after the midpoint date of the study, reflecting typical lags in fatalities and reporting. Meta-regression procedures in Stata were used to analyze the infection fatality rate (IFR) by age. Our analysis finds a exponential relationship between age and IFR for COVID-19. The estimated age-specific IFR is very low for children and younger adults (e.g., 0.002% at age 10 and 0.01% at age 25) but increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85. Moreover, our results indicate that about 90% of the variation in population IFR across geographical locations reflects differences in the age composition of the population and the extent to which relatively vulnerable age groups were exposed to the virus. These results indicate that COVID-19 is hazardous not only for the elderly but also for middle-aged adults, for whom the infection fatality rate is two orders of magnitude greater than the annualized risk of a fatal automobile accident and far more dangerous than seasonal influenza. Moreover, the overall IFR for COVID-19 should not be viewed as a fixed parameter but as intrinsically linked to the age-specific pattern of infections. Consequently, public health measures to mitigate infections in older adults could substantially decrease total deaths. Electronic supplementary material The online version of this article (10.1007/s10654-020-00698-1) contains supplementary material, which is available to authorized users.
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              Comparison of the characteristics, morbidity, and mortality of COVID-19 and seasonal influenza: a nationwide, population-based retrospective cohort study

              Background To date, influenza epidemics have been considered suitable for use as a model for the COVID-19 epidemic, given that they are respiratory diseases with similar modes of transmission. However, data directly comparing the two diseases are scarce. Methods We did a nationwide retrospective cohort study using the French national administrative database (PMSI), which includes discharge summaries for all hospital admissions in France. All patients hospitalised for COVID-19 from March 1 to April 30, 2020, and all patients hospitalised for influenza between Dec 1, 2018, and Feb 28, 2019, were included. The diagnosis of COVID-19 (International Classification of Diseases [10th edition] codes U07.10, U07.11, U07.12, U07.14, or U07.15) or influenza (J09, J10, or J11) comprised primary, related, or associated diagnosis. Comparisons of risk factors, clinical characteristics, and outcomes between patients hospitalised for COVID-19 and influenza were done, with data also stratified by age group. Findings 89 530 patients with COVID-19 and 45 819 patients with influenza were hospitalised in France during the respective study periods. The median age of patients was 68 years (IQR 52–82) for COVID-19 and 71 years (34–84) for influenza. Patients with COVID-19 were more frequently obese or overweight, and more frequently had diabetes, hypertension, and dyslipidaemia than patients with influenza, whereas those with influenza more frequently had heart failure, chronic respiratory disease, cirrhosis, and deficiency anaemia. Patients admitted to hospital with COVID-19 more frequently developed acute respiratory failure, pulmonary embolism, septic shock, or haemorrhagic stroke than patients with influenza, but less frequently developed myocardial infarction or atrial fibrillation. In-hospital mortality was higher in patients with COVID-19 than in patients with influenza (15 104 [16·9%] of 89 530 vs 2640 [5·8%] of 45 819), with a relative risk of death of 2·9 (95% CI 2·8–3·0) and an age-standardised mortality ratio of 2·82. Of the patients hospitalised, the proportion of paediatric patients (<18 years) was smaller for COVID-19 than for influenza (1227 [1·4%] vs 8942 [19·5%]), but a larger proportion of patients younger than 5 years needed intensive care support for COVID-19 than for influenza (14 [2·3%] of 613 vs 65 [0·9%] of 6973). In adolescents (11–17 years), the in-hospital mortality was ten-times higher for COVID-19 than for influenza (five [1·1% of 458 vs one [0·1%] of 804), and patients with COVID-19 were more frequently obese or overweight. Interpretation The presentation of patients with COVID-19 and seasonal influenza requiring hospitalisation differs considerably. Severe acute respiratory syndrome coronavirus 2 is likely to have a higher potential for respiratory pathogenicity, leading to more respiratory complications and to higher mortality. In children, although the rate of hospitalisation for COVID-19 appears to be lower than for influenza, in-hospital mortality is higher; however, low patient numbers limit this finding. These findings highlight the importance of appropriate preventive measures for COVID-19, as well as the need for a specific vaccine and treatment. Funding French National Research Agency.
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                Author and article information

                Contributors
                Journal
                Int J Epidemiol
                Int J Epidemiol
                ije
                International Journal of Epidemiology
                Oxford University Press
                0300-5771
                1464-3685
                April 2023
                28 February 2023
                28 February 2023
                : 52
                : 2
                : 355-376
                Affiliations
                Medical Research Council (MRC) Population Health Research Unit, Clinical Trials Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford , Oxford, UK
                Roslin Institute, University of Edinburgh , Edinburgh, UK
                Intensive Care Unit, Royal Infirmary of Edinburgh , Edinburgh, UK
                Hospital 12 de Octubre , Madrid, Spain
                International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Global Support Centre, Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford , Oxford, UK
                Critical Care Asia , Bangkok, Thailand
                National Institute for Communicable Diseases , Johannesburg, South Africa
                National Institute of Infectious Disease Evandro Chagas, Oswaldo Cruz Foundation (INI-FIOCRUZ), Ministry of Health, and D'Or Institute of Research and Education (IDOR) , Rio de Janeiro, São Paulo, Brazil
                Monash University , Clayton, Melbourne, Australia
                Monash University , Clayton, Melbourne, Australia
                International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Global Support Centre, Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford , Oxford, UK
                International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Global Support Centre, Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford , Oxford, UK
                International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Global Support Centre, Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford , Oxford, UK
                Department of Statistics, University of Oxford , Oxford, UK
                Department of Statistics, University of Oxford , Oxford, UK
                MRC Centre for Global Infectious Disease Analysis, Abdul Latif Jameel Institute for Disease and Emergency Analytics and Department of Infectious Disease Epidemiology, Imperial College London , London, UK
                International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Global Support Centre, Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford , Oxford, UK
                CHU Caremeau , Nîmes, France
                International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Global Support Centre, Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford , Oxford, UK
                Humber River Hospital , Toronto, Canada
                Cliniques Universitaires de Bruxelles (CUB) Hopital Erasme , Anderlecht, Belgium
                International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Global Support Centre, Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford , Oxford, UK
                Big Data Institute, Nuffield Department of Medicine, University of Oxford , Oxford, UK
                Critical Care Asia and Ziauddin University , Karachi, Pakistan
                Hospital Sungai Buloh, Ministry of Health , Sungai Buloh, Malaysia
                Medical Research Council-University of Glasgow Centre for Virus Research, Glasgow, UK Department of Infectious Diseases, Queen Elizabeth University Hospital , Glasgow, UK
                National Institute for Communicable Diseases , Johannesburg, South Africa
                Hospital 12 de Octubre , Madrid, Spain
                Un iversité de Paris, France, Infection, Antimicrobials, Modelling, Evolution (IAME), INSERM , Paris, France
                Malawi-Liverpool Wellcome Trust , Blantyre, Malawi
                St James's Hospital , Dublin, Ireland
                Un iversité de Paris, France, Infection, Antimicrobials, Modelling, Evolution (IAME), INSERM , Paris, France
                International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Global Support Centre, Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford , Oxford, UK
                Infectious Diseases Data Observatory, Centre for Tropical Medicine and Global Health, University of Oxford , Oxford, UK
                Liverpool School of Tropical Medicine , Liverpool, UK
                Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child’s Health, Sechenov First Moscow State Medical University (Sechenov University) , Moscow, Russia
                Inflammation, Repair and Development Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London , London, UK
                Sechenov University , Moscow, Russia
                Irish Critical Care Critical Clinical Trials Network , Dublin, Ireland
                All India Institute of Medical Sciences (AIIMS) , Rishikesh, India
                Franciscus Gasthuis & Vlietland , Rotterdam, Netherlands
                All India Institute of Medical Sciences (AIIMS) , Rishikesh, India
                Humber River Hospital , Toronto, Canada
                International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Global Support Centre, Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford , Oxford, UK
                Apollo Hospitals Chennai , Chennai, India
                National Institute of Infectious Disease Evandro Chagas, Oswaldo Cruz Foundation (INI-FIOCRUZ), Ministry of Health, and D'Or Institute of Research and Education (IDOR) , Rio de Janeiro, São Paulo, Brazil
                CHU Caremeau , Nîmes, France
                Carol Davila University of Medicine and Pharmacy , Bucharest, Romania
                National Institute for Infectious Diseases ‘Prof. Dr. Matei Bals’ , Bucharest, Romania
                Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool , Liverpool, UK
                UK Respiratory Medicine, Alder Hey Children’s NHS Foundation Trust , Liverpool, UK
                University of Michigan Schools of Medicine & Public Health , Ann Arbor, Michigan, USA
                International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Global Support Centre, Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford , Oxford, UK
                University of Michigan Schools of Medicine & Public Health , Ann Arbor, Michigan, USA
                Carol Davila University of Medicine and Pharmacy , Bucharest, Romania
                Cliniques Universitaires de Bruxelles (CUB) Hopital Erasme , Anderlecht, Belgium
                Apollo Hospitals Chennai , Chennai, India
                Department of Critical Care Medicine, Apollo Hospitals , Chennai, India
                The George Institute for Global Health , New Delhi, India
                Big Data Institute, Nuffield Department of Medicine, University of Oxford , Oxford, UK
                Franciscus Gasthuis & Vlietland , Rotterdam, Netherlands
                National Institutes of Health (NIH), Ministry of Health , Shah Alam, Malaysia
                International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Global Support Centre, Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford , Oxford, UK
                International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Global Support Centre, Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford , Oxford, UK
                Royal Melbourne Hospital , Melbourne, Australia
                Centre for Integrated Critical Care, University of Melbourne , Melbourne, Australia
                International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Global Support Centre, Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford , Oxford, UK
                Author notes

                Members listed in Notes.

                Corresponding author. Medical Research Council Population Health Research Unit at the University of Oxford, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Big Data Institute, Old Road Campus, Oxford, OX3 7LF, UK. E-mail: christiana.kartsonaki@ 123456dph.ox.ac.uk
                Author information
                https://orcid.org/0000-0002-3981-3418
                https://orcid.org/0000-0002-6959-5749
                https://orcid.org/0000-0003-1465-3785
                https://orcid.org/0000-0002-6164-2854
                https://orcid.org/0000-0001-9652-6856
                https://orcid.org/0000-0002-9822-1586
                Article
                dyad012
                10.1093/ije/dyad012
                10114094
                36850054
                3676aa63-d454-4b91-b0ea-40790441baf9
                © The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 31 May 2022
                : 10 November 2022
                : 01 February 2023
                Page count
                Pages: 22
                Funding
                Funded by: Foreign, Commonwealth and Development Office, DOI 10.13039/501100020171;
                Funded by: Wellcome, DOI 10.13039/100004440;
                Award ID: 215091/Z/18/Z
                Award ID: 205228/Z/16/Z
                Award ID: 220757/Z/20/Z
                Funded by: Bill & Melinda Gates Foundation, DOI 10.13039/100000865;
                Award ID: OPP1209135
                Funded by: Medical Research Council Clinical Research Training;
                Award ID: MR/V001671/1
                Funded by: University of Oxford’s COVID-19 Research Response Fund;
                Funded by: CIHR Coronavirus Rapid Research Funding Opportunity;
                Award ID: OV2170359
                Funded by: Canada by Sunnybrook Research Institute;
                Funded by: Irish Critical Care—Clinical Trials Group;
                Funded by: Irish Critical Care—Clinical Trials Network;
                Funded by: University College Dublin, DOI 10.13039/501100001631;
                Funded by: Health Research Board of Ireland;
                Funded by: Rapid European COVID-19 Emergency Response research;
                Award ID: 101003589
                Funded by: European Clinical Research Alliance on Infectious Diseases;
                Award ID: 965313
                Funded by: Cambridge NIHR Biomedical Research Centre;
                Funded by: Groote Schuur Hospital Covid ICU Team;
                Funded by: Research Council of Norway, DOI 10.13039/501100005416;
                Award ID: 312780
                Funded by: NIHR, DOI 10.13039/100006662;
                Award ID: NIHR201385
                Funded by: Innovative Medicines Initiative Joint Undertaking;
                Award ID: 115523
                Funded by: European Union’s Seventh Framework Programme;
                Award ID: FP7/2007– 2013
                Funded by: Medical Research Council, DOI 10.13039/501100000265;
                Award ID: MC_PC_19059
                Funded by: NIHR Health Protection Research Unit, DOI 10.13039/100018336;
                Funded by: Emerging and Zoonotic Infections at University of Liverpool;
                Award ID: 200907
                Categories
                Covid-19
                AcademicSubjects/MED00860

                Public health
                covid-19,sars-cov-2,cohort study,risk of death,co-morbidities,symptoms,treatments
                Public health
                covid-19, sars-cov-2, cohort study, risk of death, co-morbidities, symptoms, treatments

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