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      Early changes in laboratory parameters are predictors of mortality and ICU admission in patients with COVID-19: a systematic review and meta-analysis

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          Abstract

          Despite the growing knowledge of the clinicopathological features of COVID-19, the correlation between early changes in the laboratory parameters and the clinical outcomes of patients is not entirely understood. In this study, we aimed to assess the prognostic value of early laboratory parameters in COVID-19. We conducted a systematic review and meta-analysis based on the available literature in five databases. The last search was on July 26, 2020, with key terms related to COVID-19. Eligible studies contained original data of at least ten infected patients and reported on baseline laboratory parameters of patients. We calculated weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) with 95% confidence intervals. 93 and 78 studies were included in quantitative and qualitative syntheses, respectively. Higher baseline total white blood cell count (WBC), C-reactive protein (CRP), lactate-dehydrogenase (LDH), creatine kinase (CK), D-dimer and lower absolute lymphocyte count (ALC) (WMD ALC = − 0.35 × 10 9/L [CI − 0.43, − 0.27], p < 0.001, I 2 = 94.2%; < 0.8 × 10 9/L, OR ALC = 3.74 [CI 1.77, 7.92], p = 0.001, I 2 = 65.5%) were all associated with higher mortality rate. On admission WBC, ALC, D-dimer, CRP, LDH, and CK changes could serve as alarming prognostic factors. The correct interpretation of laboratory abnormalities can guide therapeutic decisions, especially in early identification of potentially critical cases. This meta-analysis should help to allocate resources and save lives by enabling timely intervention.

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          The online version of this article (10.1007/s00430-020-00696-w) contains supplementary material, which is available to authorized users.

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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 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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              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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                Author and article information

                Contributors
                alizadeh.hussain@pte.hu
                Journal
                Med Microbiol Immunol
                Med Microbiol Immunol
                Medical Microbiology and Immunology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0300-8584
                1432-1831
                21 November 2020
                21 November 2020
                : 1-15
                Affiliations
                [1 ]GRID grid.9679.1, ISNI 0000 0001 0663 9479, Institute for Translational Medicine, , University of Pécs Medical School, ; Pécs, Hungary
                [2 ]GRID grid.9679.1, ISNI 0000 0001 0663 9479, János Szentágothai Research Centre, University of Pécs, ; Pécs, Hungary
                [3 ]GRID grid.9008.1, ISNI 0000 0001 1016 9625, First Department of Medicine, , University of Szeged, ; Szeged, Hungary
                [4 ]GRID grid.9008.1, ISNI 0000 0001 1016 9625, Doctoral School of Clinical Medicine, , University of Szeged, ; Szeged, Hungary
                [5 ]GRID grid.22254.33, ISNI 0000 0001 2205 0971, Department of Anaesthesiology and Intensive Therapy, , Poznan University for Medical Sciences, ; Poznan, Poland
                [6 ]GRID grid.9679.1, ISNI 0000 0001 0663 9479, Division of Hematology, First Department of Internal Medicine, , University of Pécs Medical School, ; Pécs, Hungary
                [7 ]GRID grid.9679.1, ISNI 0000 0001 0663 9479, Division of Gastroenterology, First Department of Internal Medicine, , University of Pécs Medical School, ; Pécs, Hungary
                [8 ]Heim Pál National Institute of Pediatrics, Budapest, Hungary
                Author notes

                Edited by Matthias J. Reddehase.

                Author information
                http://orcid.org/0000-0001-5032-866X
                http://orcid.org/0000-0003-4534-0394
                http://orcid.org/0000-0001-6953-3591
                http://orcid.org/0000-0003-4977-1079
                http://orcid.org/0000-0001-7583-5211
                http://orcid.org/0000-0001-5848-2506
                http://orcid.org/0000-0002-4609-487X
                Article
                696
                10.1007/s00430-020-00696-w
                7679241
                33219397
                6944b1a8-4433-43b6-bae4-2f4656b5aafc
                © 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/.

                History
                : 4 May 2020
                : 31 October 2020
                Funding
                Funded by: Human Resources Development Operational Programme Grant
                Award ID: EFOP–3.6.2–16–2017–00006 – LIVE LONGER
                Award Recipient :
                Funded by: University of Pécs
                Categories
                Original Investigation

                Microbiology & Virology
                covid-19,laboratory,prognosis,survival,mortality,meta-analysis
                Microbiology & Virology
                covid-19, laboratory, prognosis, survival, mortality, meta-analysis

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