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      An Artificial Intelligence Model to Predict the Mortality of COVID-19 Patients at Hospital Admission Time Using Routine Blood Samples: Development and Validation of an Ensemble Model

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          Abstract

          Background

          COVID-19, which is accompanied by acute respiratory distress, multiple organ failure, and death, has spread worldwide much faster than previously thought. However, at present, it has limited treatments.

          Objective

          To overcome this issue, we developed an artificial intelligence (AI) model of COVID-19, named EDRnet (ensemble learning model based on deep neural network and random forest models), to predict in-hospital mortality using a routine blood sample at the time of hospital admission.

          Methods

          We selected 28 blood biomarkers and used the age and gender information of patients as model inputs. To improve the mortality prediction, we adopted an ensemble approach combining deep neural network and random forest models. We trained our model with a database of blood samples from 361 COVID-19 patients in Wuhan, China, and applied it to 106 COVID-19 patients in three Korean medical institutions.

          Results

          In the testing data sets, EDRnet provided high sensitivity (100%), specificity (91%), and accuracy (92%). To extend the number of patient data points, we developed a web application (BeatCOVID19) where anyone can access the model to predict mortality and can register his or her own blood laboratory results.

          Conclusions

          Our new AI model, EDRnet, accurately predicts the mortality rate for COVID-19. It is publicly available and aims to help health care providers fight COVID-19 and improve patients’ outcomes.

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          Most cited references33

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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 Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

            In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
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              Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China

              Dear Editor, The rapid emergence of COVID-19 in Wuhan city, Hubei Province, China, has resulted in thousands of deaths [1]. Many infected patients, however, presented mild flu-like symptoms and quickly recover [2]. To effectively prioritize resources for patients with the highest risk, we identified clinical predictors of mild and severe patient outcomes. Using the database of Jin Yin-tan Hospital and Tongji Hospital, we conducted a retrospective multicenter study of 68 death cases (68/150, 45%) and 82 discharged cases (82/150, 55%) with laboratory-confirmed infection of SARS-CoV-2. Patients met the discharge criteria if they had no fever for at least 3 days, significantly improved respiratory function, and had negative SARS-CoV-2 laboratory test results twice in succession. Case data included demographics, clinical characteristics, laboratory results, treatment options and outcomes. For statistical analysis, we represented continuous measurements as means (SDs) or as medians (IQRs) which compared with Student’s t test or the Mann–Whitney–Wilcoxon test. Categorical variables were expressed as numbers (%) and compared by the χ 2 test or Fisher’s exact test. The distribution of the enrolled patients’ age is shown in Fig. 1a. There was a significant difference in age between the death group and the discharge group (p < 0.001) but no difference in the sex ratio (p = 0.43). A total of 63% (43/68) of patients in the death group and 41% (34/82) in the discharge group had underlying diseases (p = 0.0069). It should be noted that patients with cardiovascular diseases have a significantly increased risk of death when they are infected with SARS-CoV-2 (p < 0.001). A total of 16% (11/68) of the patients in the death group had secondary infections, and 1% (1/82) of the patients in the discharge group had secondary infections (p = 0.0018). Laboratory results showed that there were significant differences in white blood cell counts, absolute values of lymphocytes, platelets, albumin, total bilirubin, blood urea nitrogen, blood creatinine, myoglobin, cardiac troponin, C-reactive protein (CRP) and interleukin-6 (IL-6) between the two groups (Fig. 1b and Supplementary Table 1). Fig. 1 a Age distribution of patients with confirmed COVID-19; b key laboratory parameters for the outcomes of patients with confirmed COVID-19; c interval from onset of symptom to death of patients with confirmed COVID-19; d summary of the cause of death of 68 died patients with confirmed COVID-19 The survival times of the enrolled patients in the death group were analyzed. The distribution of survival time from disease onset to death showed two peaks, with the first one at approximately 14 days (22 cases) and the second one at approximately 22 days (17 cases) (Fig. 1c). An analysis of the cause of death was performed. Among the 68 fatal cases, 36 patients (53%) died of respiratory failure, five patients (7%) with myocardial damage died of circulatory failure, 22 patients (33%) died of both, and five remaining died of an unknown cause (Fig. 1d). Based on the analysis of the clinical data, we confirmed that some patients died of fulminant myocarditis. In this study, we first reported that the infection of SARS-CoV-2 may cause fulminant myocarditis. Given that fulminant myocarditis is characterized by a rapid progress and a severe state of illness [3], our results should alert physicians to pay attention not only to the symptoms of respiratory dysfunction but also the symptoms of cardiac injury. Further, large-scale studies and the studies on autopsy are needed to confirm our analysis. In conclusion, predictors of a fatal outcome in COVID-19 cases included age, the presence of underlying diseases, the presence of secondary infection and elevated inflammatory indicators in the blood. The results obtained from this study also suggest that COVID-19 mortality might be due to virus-activated “cytokine storm syndrome” or fulminant myocarditis. Electronic supplementary material Below is the link to the electronic supplementary material. Supplementary material 1 (DOCX 38 kb)
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                Author and article information

                Contributors
                Journal
                J Med Internet Res
                J Med Internet Res
                JMIR
                Journal of Medical Internet Research
                JMIR Publications (Toronto, Canada )
                1439-4456
                1438-8871
                December 2020
                23 December 2020
                23 December 2020
                : 22
                : 12
                : e25442
                Affiliations
                [1 ] Biomedical Engineering Wonkwang University Iksan Republic of Korea
                [2 ] Department of Trauma Surgery Wonkwang University Hospital Iksan Republic of Korea
                [3 ] Department of Internal Medicine Wonkwang University Hospital Iksan Republic of Korea
                [4 ] Department of Thoracic and Cardiovascular Surgery Chonnam National University Medical School Gwangju Republic of Korea
                [5 ] Department of Internal Medicine Chonnam National University Medical School Gwangju Republic of Korea
                [6 ] Department of Critical Care Medicine Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Republic of Korea
                [7 ] Department of Biochemistry Wonkwang University School of Medicine Iksan Republic of Korea
                [8 ] Department of Pathology Wonkwang University School of Medicine Iksan Republic of Korea
                [9 ] Biotechnology and Human Systems Lincoln Laboratory Massachusetts Institute of Technology Lexington, MA United States
                [10 ] Radiology and Research Institute of Radiology Asan Medical Center University of Ulsan College of Medicine Seoul Republic of Korea
                Author notes
                Corresponding Author: Jinseok Lee gonasago@ 123456gmail.com
                Author information
                https://orcid.org/0000-0001-7807-215X
                https://orcid.org/0000-0002-4039-1419
                https://orcid.org/0000-0003-0136-4458
                https://orcid.org/0000-0002-6031-009X
                https://orcid.org/0000-0003-2262-2882
                https://orcid.org/0000-0003-0162-6155
                https://orcid.org/0000-0003-1830-307X
                https://orcid.org/0000-0003-4945-5623
                https://orcid.org/0000-0003-1410-425X
                https://orcid.org/0000-0002-8466-7800
                https://orcid.org/0000-0002-3285-0005
                https://orcid.org/0000-0002-5493-0399
                https://orcid.org/0000-0002-1532-5970
                https://orcid.org/0000-0002-8580-490X
                Article
                v22i12e25442
                10.2196/25442
                7759509
                33301414
                d3cdd809-c4f2-46ce-9eb4-293b74c15014
                ©Hoon Ko, Heewon Chung, Wu Seong Kang, Chul Park, Do Wan Kim, Seong Eun Kim, Chi Ryang Chung, Ryoung Eun Ko, Hooseok Lee, Jae Ho Seo, Tae-Young Choi, Rafael Jaimes, Kyung Won Kim, Jinseok Lee. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 23.12.2020.

                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 use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research, is properly cited. The complete bibliographic information, a link to the original publication on http://www.jmir.org/, as well as this copyright and license information must be included.

                History
                : 3 November 2020
                : 24 November 2020
                : 24 November 2020
                : 8 December 2020
                Categories
                Original Paper
                Original Paper

                Medicine
                covid-19,artificial intelligence,blood samples,mortality prediction
                Medicine
                covid-19, artificial intelligence, blood samples, mortality prediction

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