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      Dynamic changes of D-dimer and neutrophil-lymphocyte count ratio as prognostic biomarkers in COVID-19

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          Abstract

          Background

          Since December 2019, the outbreak of COVID-19 caused a large number of hospital admissions in China. Many patients with COVID-19 have symptoms of acute respiratory distress syndrome, even are in danger of death. This is the first study to evaluate dynamic changes of D-Dimer and Neutrophil-Lymphocyte Count Ratio (NLR) as a prognostic utility in patients with COVID-19 for clinical use.

          Methods

          In a retrospective study, we collected data from 349 hospitalized patients who diagnosed as the infection of the COVID-19 in Wuhan Pulmonary Hospital. We used ROC curves and Cox regression analysis to explore critical value (optimal cut-off point associated with Youden index) and prognostic role of dynamic changes of D-Dimer and NLR.

          Results

          Three hundred forty-nine participants were enrolled in this study and the mortality rate of the patients with laboratory diagnosed COVID-19 was 14.9%. The initial and peak value of D-Dimer and NLR in deceased patients were higher statistically compared with survivors ( P < 0.001). There was a more significant upward trend of D-Dimer and NLR during hospitalization in the deceased patients, initial D-Dimer and NLR were lower than the peak tests (MD) -25.23, 95% CI: − 31.81- -18.64, P < 0.001; (MD) -43.73, 95% CI:-59.28- -31.17, P < 0.001. The test showed a stronger correlation between hospitalization days, PCT and peak D-Dimer than initial D-Dimer. The areas under the ROC curves of peak D-Dimer and peak NLR tests were higher than the initial tests (0.94(95%CI: 0.90–0.98) vs. 0.80 (95% CI: 0.73–0.87); 0.93 (95%CI:0.90–0.96) vs. 0.86 (95%CI:0.82–0.91). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR was 0.73 mg/L, 3.78 mg/L,7.13 and 14.31 respectively. 35 (10.03%) patients were intubated. In the intubated patients, initial and peak D-Dimer and NLR were much higher than non-intubated patients ( P < 0.001). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR in prognosticate of intubation was 0.73 mg/L, 12.75 mg/L,7.28 and 27.55. The multivariable Cox regression analysis showed that age (HR 1.04, 95% CI 1.00–1.07, P = 0.01), the peak D-Dimer (HR 1.03, 95% CI 1.01–1.04, P < 0.001) were prognostic factors for COVID-19 patients’ death.

          Conclusions

          To dynamically observe the ratio of D-Dimer and NLR was more valuable during the prognosis of COVID-19. The rising trend in D-Dimer and NLR, or the test results higher than the critical values may indicate a risk of death for participants with COVID-19.

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          Most cited references14

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          A Novel Coronavirus from Patients with Pneumonia in China, 2019

          Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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            Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

            Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.
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              A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)

              In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named “2019 novel coronavirus (2019-nCoV)” by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.
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                Author and article information

                Contributors
                yewenjing@xinhuamed.com.cn
                4799082@qq.com
                xiaopanli0224@126.com
                474137452@qq.com
                c.ji.3@warwick.ac.uk
                min-hou710@hotmail.com
                zhangdizhangdi1234@163.com
                785663609@qq.com
                953822402@qq.com
                xucheng112358@126.com
                luweiwei100@126.com
                crlqwerty@163.com
                caiyuyang@sjtu.edu.cn
                1220775601@qq.com
                yangling01@xinhuamed.com.cn
                Journal
                Respir Res
                Respir. Res
                Respiratory Research
                BioMed Central (London )
                1465-9921
                1465-993X
                3 July 2020
                3 July 2020
                2020
                : 21
                : 169
                Affiliations
                [1 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Respiratory Medicine, Xinhua Hospital, School of Medicine, , Shanghai Jiao Tong University, ; Shanghai, 200092 China
                [2 ]Department of Tuberculosis ward 2, Wuhan Pulmonary Hospital, Wuhan, 430030 Hubei China
                [3 ]Center for Disease Control and Prevention, Pudong New Area, Shanghai, 200136 China
                [4 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Fudan University Pudong Institute of Preventive Medicine, ; Pudong New Area, Shanghai, 200136 China
                [5 ]GRID grid.7372.1, ISNI 0000 0000 8809 1613, Warwick Clinical Trials Unit, , Warwick Medical School, ; Coventry, UK
                [6 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, School of Public Health, , Shanghai Jiao Tong University School of Medicine, ; Shanghai, 200025 China
                [7 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Geriatrics, Xinhua Hospital, School of Medicine, , Institute of Hospital Development Strategy, China Hospital Development Institute, Shanghai Jiao Tong University, ; Shanghai, 200092 China
                [8 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Emergency, Xinhua Hospital, School of Medicine, , Shanghai Jiao Tong University, ; Shanghai, 200092 China
                [9 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Chinese Medicine, Xinhua Hospital, School of Medicine, , Shanghai Jiao Tong University, ; Shanghai, 200092 China
                Article
                1428
                10.1186/s12931-020-01428-7
                7332531
                32620118
                4a8d8a4e-3626-43be-bc29-a63721d9c878
                © The Author(s) 2020

                Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 8 April 2020
                : 18 June 2020
                Funding
                Funded by: Zhejiang University special scientific research fund for COVID-19 prevention and control
                Award ID: 2020XGZX065
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Respiratory medicine
                covid-19,d-dimer,neutrophil-lymphocyte count ratio,prognostic biomarker,cox regression

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