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      Radiomics Analysis of Computed Tomography helps predict poor prognostic outcome in COVID-19

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          Abstract

          Rationale: Given the rapid spread of COVID-19, an updated risk-stratify prognostic tool could help clinicians identify the high-risk patients with worse prognoses. We aimed to develop a non-invasive and easy-to-use prognostic signature by chest CT to individually predict poor outcome (death, need for mechanical ventilation, or intensive care unit admission) in patients with COVID-19.

          Methods: From November 29, 2019 to February 19, 2020, a total of 492 patients with COVID-19 from four centers were retrospectively collected. Since different durations from symptom onsets to the first CT scanning might affect the prognostic model, we designated the 492 patients into two groups: 1) the early-phase group: CT scans were performed within one week after symptom onset (0-6 days, n = 317); and 2) the late-phase group: CT scans were performed one week later after symptom onset (≥7 days, n = 175). In each group, we divided patients into the primary cohort (n = 212 in the early-phase group, n = 139 in the late-phase group) and the external independent validation cohort (n = 105 in the early-phase group, n = 36 in the late-phase group) according to the centers. We built two separate radiomics models in the two patient groups. Firstly, we proposed an automatic segmentation method to extract lung volume for radiomics feature extraction. Secondly, we applied several image preprocessing procedures to increase the reproducibility of the radiomics features: 1) applied a low-pass Gaussian filter before voxel resampling to prevent aliasing; 2) conducted ComBat to harmonize radiomics features per scanner; 3) tested the stability of the features in the radiomics signature by several image transformations, such as rotating, translating, and growing/shrinking. Thirdly, we used least absolute shrinkage and selection operator (LASSO) to build the radiomics signature (RadScore). Afterward, we conducted a Fine-Gray competing risk regression to build the clinical model and the clinic-radiomics signature (CrrScore). Finally, performances of the three prognostic signatures (clinical model, RadScore, and CrrScore) were estimated from the two aspects: 1) cumulative poor outcome probability prediction; 2) 28-day poor outcome prediction. We also did stratified analyses to explore the potential association between the CrrScore and the poor outcomes regarding different age, type, and comorbidity subgroups.

          Results: In the early-phase group, the CrrScore showed the best performance in estimating poor outcome (C-index = 0.850), and predicting the probability of 28-day poor outcome (AUC = 0.862). In the late-phase group, the RadScore alone achieved similar performance to the CrrScore in predicting poor outcome (C-index = 0.885), and 28-day poor outcome probability (AUC = 0.976). Moreover, the RadScore in both groups successfully stratified patients with COVID-19 into low- or high-RadScore groups with significantly different survival time in the training and validation cohorts (all P < 0.05). The CrrScore in both groups can also significantly stratify patients with different prognoses regarding different age, type, and comorbidities subgroups in the combined cohorts (all P < 0.05).

          Conclusions: This research proposed a non-invasive and quantitative prognostic tool for predicting poor outcome in patients with COVID-19 based on CT imaging. Taking the insufficient medical recourse into account, our study might suggest that the chest CT radiomics signature of COVID-19 is more effective and ideal to predict poor outcome in the late-phase COVID-19 patients. For the early-phase patients, integrating radiomics signature with clinical risk factors can achieve a more accurate prediction of individual poor prognostic outcome, which enables appropriate management and surveillance of COVID-19.

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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

                Journal
                Theranostics
                Theranostics
                thno
                Theranostics
                Ivyspring International Publisher (Sydney )
                1838-7640
                2020
                5 June 2020
                : 10
                : 16
                : 7231-7244
                Affiliations
                [1 ]College of Medicine and Biomedical Information Engineering, Northeastern University, Shenyang, Liaoning, 110819, China.
                [2 ]Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University, Beijing, 100191, China.
                [3 ]Department of Radiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
                [4 ]Department of medical imaging, Henan Provincial People's Hospital; People's Hospital of Zhengzhou University; People's Hospital of Henan University; Zhengzhou, Henan, 450003, China.
                [5 ]Department of Electrical and Computer Engineering, University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968, United States.
                [6 ]Department of Radiology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Hubei, 435000, China
                [7 ]Department of Radiology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China.
                [8 ]Engineering Research Center of Molecular and Neuro Imaging of Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China.
                [9 ]CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China.
                Author notes
                ✉ Corresponding authors: Jie Tian, Ph.D. Fellow of AIMBE, IAMBE, ISMRM, IEEE, SPIE, OSA, IAPR, Director of the CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, China, No.95 Zhongguancun east road, Beijing 100190, China. E-mail: jie.tian@ 123456ia.ac.cn ; Tel: +86-10-82618465, Fax: +86-10-62527995; Yunfei Zha, M.D. Department of Radiology, Renmin Hospital of Wuhan University, Wuhan 430060, China, No.238, Jiefang Road, Wuchang District, Wuhan, E-mail: zhayunfei999@ 123456126.com , Tel: 13006188899; Xiaoming Qiu, M.D. Department of Radiology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, E-mail: qxm2020cov@ 123456163.com ; Meiyun Wang, M.D. No. 7 Weiwu Road, Zhengzhou, Henan 450003, China, E-mail: mywang@ 123456ha.edu.cn , Tel: +86-13837101920, Fax: +86-371-6596-4376; Hongjun Li, M.D. Department of Radiology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China, E-mail: lihongjun00113@ 123456126.com ; He Ma, Ph.D. College of Medicine and Biomedical Information Engineering, Northeastern University, Shenyang, Liaoning 110819, China, E-mail: mahe@ 123456bmie.neu.edu.cn , Tel: +86-18524442165, Fax: +86-24-83676662.

                *Equal contributions to this work.

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                thnov10p7231
                10.7150/thno.46428
                7330838
                32641989
                50c2d3c5-445f-41ac-a89d-b953b2614995
                © The author(s)

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 28 March 2020
                : 16 May 2020
                Categories
                Research Paper

                Molecular medicine
                covid-19,computed tomography,radiomics,prognosis,poor outcome
                Molecular medicine
                covid-19, computed tomography, radiomics, prognosis, poor outcome

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