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      Immune-Inflammatory Parameters in COVID-19 Cases: A Systematic Review and Meta-Analysis

      systematic-review

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          Abstract

          Background: The recent outbreak of coronavirus disease 2019 (COVID-19) has been rapidly spreading on a global scale and poses a great threat to human health. Acute respiratory distress syndrome, characterized by a rapid onset of generalized inflammation, is the leading cause of mortality in patients with COVID-19. We thus aimed to explore the effect of risk factors on the severity of the disease, focusing on immune-inflammatory parameters, which represent the immune status of patients.

          Methods: A comprehensive systematic search for relevant studies published up to April 2020 was performed by using the PubMed, Web of Science, EMBASE, and China National Knowledge Internet (CNKI) databases. After extracting all available data of immune-inflammatory indicators, we statistically analyzed the risk factors of severe and non-severe COVID-19 patients with a meta-analysis.

          Results: A total of 4,911 patients from 29 studies were included in the final meta-analysis. The results demonstrated that severe patients tend to present with increased white blood cell (WBC) and neutrophil counts, neutrophil-lymphocyte ratio (NLR), procalcitonin (PCT), C-reaction protein (CRP), erythrocyte sedimentation rate (ESR), and Interleukin-6 (IL-6) and a decreased number of total lymphocyte and lymphocyte subtypes, such as CD4+ T lymphocyte and CD8+ T lymphocyte, compared to the non-severe patients. In addition, the WBC count>10 × 10 9/L, lymphocyte count<1 × 10 9/L, PCT>0.5 ng/mL, and CRP>10 mg/L were risk factors for disease progression in patients with COVID-19 (WBC count>10 × 10 9/L: OR = 2.92, 95% CI: 1.96–4.35; lymphocyte count<1 × 10 9/L: OR = 4.97, 95% CI: 3.53–6.99; PCT>0.5 ng/mL: OR = 6.33, 95% CI: 3.97–10.10; CRP>10 mg/L: OR = 3.51, 95% CI: 2.38–5.16). Furthermore, we found that NLR, as a novel marker of systemic inflammatory response, can also help predict clinical severity in patients with COVID-19 (OR = 2.50, 95% CI: 2.04–3.06).

          Conclusions: Immune-inflammatory parameters, such as WBC, lymphocyte, PCT, CRP, and NLR, could imply the progression of COVID-19. NLR has taken both the levels of neutrophil and lymphocyte into account, indicating a more complete, accurate, and reliable inspection efficiency; surveillance of NLR may help clinicians identify high-risk COVID-19 patients at an early stage.

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          Most cited references54

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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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            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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              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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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                09 June 2020
                2020
                09 June 2020
                : 7
                : 301
                Affiliations
                [1] 1State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, College of Medicine, The First Affiliated Hospital, Zhejiang University , Hangzhou, China
                [2] 2Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center , Beijing, China
                [3] 3Jiangsu Key Laboratory of Biological Cancer, Cancer Institute, Xuzhou Medical University , Xuzhou, China
                [4] 4Department of General Surgery, The First Affiliated Hospital of Anhui Medical University , Hefei, China
                Author notes

                Edited by: Zisis Kozlakidis, International Agency for Research on Cancer (IARC), France

                Reviewed by: Pedro Xavier-Elsas, Federal University of Rio de Janeiro, Brazil; Pietro Ghezzi, Brighton and Sussex Medical School, United Kingdom

                *Correspondence: Bo Chen chenbo831116@ 123456163.com

                This article was submitted to Infectious Diseases – Surveillance, Prevention and Treatment, a section of the journal Frontiers in Medicine

                †These authors have contributed equally to this work

                Article
                10.3389/fmed.2020.00301
                7295898
                32582743
                2ea2b843-effc-4e69-83a8-6776a0a79e31
                Copyright © 2020 Feng, Li, Sun, Zhu, Chen, Xiong and Cao.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 05 May 2020
                : 26 May 2020
                Page count
                Figures: 7, Tables: 3, Equations: 0, References: 54, Pages: 14, Words: 7108
                Categories
                Medicine
                Systematic Review

                covid-19,immune-inflammatory parameters,neutrophil-lymphocyte ratio,risk factor,meta-analysis

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