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      Prediction models for diagnosis and prognosis of covid-19 infection: systematic review and critical appraisal

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          Abstract

          Objective

          To review and critically appraise published and preprint reports of prediction models for diagnosing coronavirus disease 2019 (covid-19) in patients with suspected infection, for prognosis of patients with covid-19, and for detecting people in the general population at risk of being admitted to hospital for covid-19 pneumonia.

          Design

          Rapid systematic review and critical appraisal.

          Data sources

          PubMed and Embase through Ovid, Arxiv, medRxiv, and bioRxiv up to 24 March 2020.

          Study selection

          Studies that developed or validated a multivariable covid-19 related prediction model.

          Data extraction

          At least two authors independently extracted data using the CHARMS (critical appraisal and data extraction for systematic reviews of prediction modelling studies) checklist; risk of bias was assessed using PROBAST (prediction model risk of bias assessment tool).

          Results

          2696 titles were screened, and 27 studies describing 31 prediction models were included. Three models were identified for predicting hospital admission from pneumonia and other events (as proxy outcomes for covid-19 pneumonia) in the general population; 18 diagnostic models for detecting covid-19 infection (13 were machine learning based on computed tomography scans); and 10 prognostic models for predicting mortality risk, progression to severe disease, or length of hospital stay. Only one study used patient data from outside of China. The most reported predictors of presence of covid-19 in patients with suspected disease included age, body temperature, and signs and symptoms. The most reported predictors of severe prognosis in patients with covid-19 included age, sex, features derived from computed tomography scans, C reactive protein, lactic dehydrogenase, and lymphocyte count. C index estimates ranged from 0.73 to 0.81 in prediction models for the general population (reported for all three models), from 0.81 to more than 0.99 in diagnostic models (reported for 13 of the 18 models), and from 0.85 to 0.98 in prognostic models (reported for six of the 10 models). All studies were rated at high risk of bias, mostly because of non-representative selection of control patients, exclusion of patients who had not experienced the event of interest by the end of the study, and high risk of model overfitting. Reporting quality varied substantially between studies. Most reports did not include a description of the study population or intended use of the models, and calibration of predictions was rarely assessed.

          Conclusion

          Prediction models for covid-19 are quickly entering the academic literature to support medical decision making at a time when they are urgently needed. This review indicates that proposed models are poorly reported, at high risk of bias, and their reported performance is probably optimistic. Immediate sharing of well documented individual participant data from covid-19 studies is needed for collaborative efforts to develop more rigorous prediction models and validate existing ones. The predictors identified in included studies could be considered as candidate predictors for new models. Methodological guidance should be followed because unreliable predictions could cause more harm than benefit in guiding clinical decisions. Finally, studies should adhere to the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) reporting guideline.

          Systematic review registration

          Protocol https://osf.io/ehc47/, registration https://osf.io/wy245.

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          Most cited references20

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          Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

          Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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            An interactive web-based dashboard to track COVID-19 in real time

            In December, 2019, a local outbreak of pneumonia of initially unknown cause was detected in Wuhan (Hubei, China), and was quickly determined to be caused by a novel coronavirus, 1 namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak has since spread to every province of mainland China as well as 27 other countries and regions, with more than 70 000 confirmed cases as of Feb 17, 2020. 2 In response to this ongoing public health emergency, we developed an online interactive dashboard, hosted by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University, Baltimore, MD, USA, to visualise and track reported cases of coronavirus disease 2019 (COVID-19) in real time. The dashboard, first shared publicly on Jan 22, illustrates the location and number of confirmed COVID-19 cases, deaths, and recoveries for all affected countries. It was developed to provide researchers, public health authorities, and the general public with a user-friendly tool to track the outbreak as it unfolds. All data collected and displayed are made freely available, initially through Google Sheets and now through a GitHub repository, along with the feature layers of the dashboard, which are now included in the Esri Living Atlas. The dashboard reports cases at the province level in China; at the city level in the USA, Australia, and Canada; and at the country level otherwise. During Jan 22–31, all data collection and processing were done manually, and updates were typically done twice a day, morning and night (US Eastern Time). As the outbreak evolved, the manual reporting process became unsustainable; therefore, on Feb 1, we adopted a semi-automated living data stream strategy. Our primary data source is DXY, an online platform run by members of the Chinese medical community, which aggregates local media and government reports to provide cumulative totals of COVID-19 cases in near real time at the province level in China and at the country level otherwise. Every 15 min, the cumulative case counts are updated from DXY for all provinces in China and for other affected countries and regions. For countries and regions outside mainland China (including Hong Kong, Macau, and Taiwan), we found DXY cumulative case counts to frequently lag behind other sources; we therefore manually update these case numbers throughout the day when new cases are identified. To identify new cases, we monitor various Twitter feeds, online news services, and direct communication sent through the dashboard. Before manually updating the dashboard, we confirm the case numbers with regional and local health departments, including the respective centres for disease control and prevention (CDC) of China, Taiwan, and Europe, the Hong Kong Department of Health, the Macau Government, and WHO, as well as city-level and state-level health authorities. For city-level case reports in the USA, Australia, and Canada, which we began reporting on Feb 1, we rely on the US CDC, the government of Canada, the Australian Government Department of Health, and various state or territory health authorities. All manual updates (for countries and regions outside mainland China) are coordinated by a team at Johns Hopkins University. The case data reported on the dashboard aligns with the daily Chinese CDC 3 and WHO situation reports 2 for within and outside of mainland China, respectively (figure ). Furthermore, the dashboard is particularly effective at capturing the timing of the first reported case of COVID-19 in new countries or regions (appendix). With the exception of Australia, Hong Kong, and Italy, the CSSE at Johns Hopkins University has reported newly infected countries ahead of WHO, with Hong Kong and Italy reported within hours of the corresponding WHO situation report. Figure Comparison of COVID-19 case reporting from different sources Daily cumulative case numbers (starting Jan 22, 2020) reported by the Johns Hopkins University Center for Systems Science and Engineering (CSSE), WHO situation reports, and the Chinese Center for Disease Control and Prevention (Chinese CDC) for within (A) and outside (B) mainland China. Given the popularity and impact of the dashboard to date, we plan to continue hosting and managing the tool throughout the entirety of the COVID-19 outbreak and to build out its capabilities to establish a standing tool to monitor and report on future outbreaks. We believe our efforts are crucial to help inform modelling efforts and control measures during the earliest stages of the outbreak.
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              Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis

              Introduction An epidemic of Coronavirus Disease 2019 (COVID-19) began in December 2019 in China leading to a Public Health Emergency of International Concern (PHEIC). Clinical, laboratory, and imaging features have been partially characterized in some observational studies. No systematic reviews on COVID-19 have been published to date. Methods We performed a systematic literature review with meta-analysis, using three databases to assess clinical, laboratory, imaging features, and outcomes of COVID-19 confirmed cases. Observational studies and also case reports, were included, and analyzed separately. We performed a random-effects model meta-analysis to calculate pooled prevalences and 95% confidence intervals (95%CI). Results 660 articles were retrieved for the time frame (1/1/2020-2/23/2020). After screening, 27 articles were selected for full-text assessment, 19 being finally included for qualitative and quantitative analyses. Additionally, 39 case report articles were included and analyzed separately. For 656 patients, fever (88.7%, 95%CI 84.5–92.9%), cough (57.6%, 95%CI 40.8–74.4%) and dyspnea (45.6%, 95%CI 10.9–80.4%) were the most prevalent manifestations. Among the patients, 20.3% (95%CI 10.0–30.6%) required intensive care unit (ICU), 32.8% presented with acute respiratory distress syndrome (ARDS) (95%CI 13.7–51.8), 6.2% (95%CI 3.1–9.3) with shock. Some 13.9% (95%CI 6.2–21.5%) of hospitalized patients had fatal outcomes (case fatality rate, CFR). Conclusion COVID-19 brings a huge burden to healthcare facilities, especially in patients with comorbidities. ICU was required for approximately 20% of polymorbid, COVID-19 infected patients and hospitalization was associated with a CFR of >13%. As this virus spreads globally, countries need to urgently prepare human resources, infrastructure and facilities to treat severe COVID-19.
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                Author and article information

                Contributors
                Role: assistant professor
                Role: associate professor
                Role: professor
                Role: professor
                Role: assistant professor
                Role: associate professor
                Role: medical doctor
                Role: associate professor
                Role: professor
                Role: professor
                Role: assistant professor
                Role: professor
                Role: lecturer
                Role: professor
                Role: research fellow
                Role: assistant professor
                Journal
                BMJ
                BMJ
                BMJ-UK
                bmj
                The BMJ
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2020
                7 April 2020
                : 369
                Affiliations
                [1 ]Department of Epidemiology, CAPHRI Care and Public Health Research Institute, Maastricht University, Peter Debyeplein 1, 6229 HA Maastricht, Netherlands
                [2 ]Department of Development and Regeneration, KU Leuven, Leuven, Belgium
                [3 ]Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, Netherlands
                [4 ]Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, Netherlands
                [5 ]Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, Netherlands
                [6 ]Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Musculoskeletal Sciences, University of Oxford, Oxford, UK
                [7 ]NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK
                [8 ]Cochrane Netherlands, University Medical Centre Utrecht, Utrecht University, Utrecht, Netherlands
                [9 ]Department of Electrical Engineering, ESAT Stadius, KU Leuven, Leuven, Belgium
                [10 ]Section for Clinical Biometrics, Centre for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria
                [11 ]Ordensklinikum Linz, Hospital Elisabethinen, Department of Nephrology, Linz, Austria
                [12 ]Centre for Prognosis Research, School of Primary, Community and Social Care, Keele University, Keele, UK
                [13 ]Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
                [14 ]Berlin Institute of Health, Berlin, Germany
                Author notes
                Article
                wynl056013
                10.1136/bmj.m1328
                7222643
                32265220
                4c06ff78-1cc9-441e-98f0-d524ff57a0c1
                © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

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