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      Machine learning based early warning system enables accurate mortality risk prediction for COVID-19

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          Abstract

          Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients’ clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464–0.9778), 0.9760 (0.9613–0.9906), and 0.9246 (0.8763–0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.

          Abstract

          Methods to stratify patients according to mortality risk are essential to allocate limited heath resources during the COVID-19 crisis. Here, using machine learning methods, the authors present a mortality risk prediction model for COVID-19 that uses patients’ clinical data on admission to stratify patients by mortality risk.

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          Most cited references35

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical Characteristics of Coronavirus Disease 2019 in China

            Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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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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                Author and article information

                Contributors
                yeyuanbei@hotmail.com
                qingleigao@hotmail.com
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                6 October 2020
                6 October 2020
                2020
                : 11
                : 5033
                Affiliations
                [1 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, National Medical Center for Major Public Health Events, Tongji Hospital, Tongji Medical College, , Huazhong University of Science and Technology, ; Wuhan, 430000 China
                [2 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, , Huazhong University of Science and Technology, ; Wuhan, 430000 China
                [3 ]GRID grid.49470.3e, ISNI 0000 0001 2331 6153, GNSS Research Center, , Wuhan University, ; Wuhan, 430079 China
                [4 ]GRID grid.464255.4, City University of Hong Kong Shenzhen Research Institute, ; Shenzhen, 518000 China
                [5 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Department of Gastroenterology, Tongji Hospital, Tongji Medical College, , Huazhong University of Science and Technology, ; Wuhan, 430000 China
                [6 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College, , Huazhong University of Science and Technology, ; Wuhan, China
                [7 ]GRID grid.452911.a, ISNI 0000 0004 1799 0637, Department of Obstetrics and Gynecology, Xiangyang Central Hospital, , Affiliated Hospital of Hubei University of Arts and Science, ; Xiangyang, Hubei China
                [8 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Department of Hematology, Tongji Hospital, Tongji Medical College, , Huazhong University of Science and Technology, ; Wuhan, 430000 China
                [9 ]GRID grid.33199.31, ISNI 0000 0004 0368 7223, Department of Neurosurgery, Tongji Hospital, Tongji Medical College, , Huazhong University of Science and Technology, ; Wuhan, 430000 China
                Author information
                http://orcid.org/0000-0002-1161-4943
                http://orcid.org/0000-0003-2915-9157
                http://orcid.org/0000-0002-0546-0239
                http://orcid.org/0000-0002-9448-3423
                Article
                18684
                10.1038/s41467-020-18684-2
                7538910
                33024092
                9a8a6dd0-42f5-4286-9bd1-b21929bb3283
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 22 May 2020
                : 27 August 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 81974405
                Award ID: 81873452
                Award ID: 81772787
                Award Recipient :
                Funded by: Nature Science Foundation of Hubei Province ;2019CFB453;.
                Funded by: National Science and Technology Major Sub-Project (2018ZX10301402-002) Technical Innovation Special Project of Hubei Province (2018ACA138) Fundamental Research Funds for the Central Universities (2019kfyXMBZ024)
                Categories
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                © The Author(s) 2020

                Uncategorized
                machine learning,prognostic markers,viral infection,risk factors
                Uncategorized
                machine learning, prognostic markers, viral infection, risk factors

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