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      The Neutrophil-to-Lymphocyte Ratio Determines Clinical Efficacy of Corticosteroid Therapy in Patients with COVID-19

      brief-report
      1 , 3 , 4 , 22 , 1 , 3 , 22 , 1 , 3 , 5 , 22 , 1 , 3 , 22 , 2 , 14 , 22 , 1 , 2 , 3 , 1 , 2 , 3 , 1 , 3 , 3 , 6 , 1 , 3 , 1 , 3 , 1 , 3 , 1 , 3 , 2 , 3 , 2 , 3 , 1 , 3 , 2 , 3 , 6 , 3 , 6 , 3 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 1 , 2 , 3 , 19 , 20 , 21 , , 1 , 3 , ∗∗ , 2 , 14 , ∗∗∗ , 1 , 2 , 3 , ∗∗∗∗ , 1 , 2 , 3 , 6 , 23 , ∗∗∗∗∗
      Cell Metabolism
      Elsevier Inc.
      COVID-19, corticosteroids, inflammatory status, neutrophil-to-lymphocyte ratio, mortality

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          Abstract

          Corticosteroid therapy is now recommended as a treatment in patients with severe COVID-19. But one key question is how to objectively identify severely ill patients who may benefit from such therapy. Here, we assigned 12,862 COVID-19 cases from 21 hospitals in Hubei Province equally to a training and a validation cohort. We found that a neutrophil-to-lymphocyte ratio (NLR) > 6.11 at admission discriminated a higher risk for mortality. Importantly, however, corticosteroid treatment in such individuals was associated with a lower risk of 60-day all-cause mortality. Conversely, in individuals with an NLR ≤ 6.11 or with type 2 diabetes, corticosteroid treatment was not associated with reduced mortality, but rather increased risks of hyperglycemia and infections. These results show that in the studied cohort corticosteroid treatment is associated with beneficial outcomes in a subset of COVID-19 patients who are non-diabetic and with severe symptoms as defined by NLR.

          Graphical Abstract

          Highlights

          • 12,862 COVID-19 cases on corticosteroid therapy or not were retrospectively studied

          • NLR at admission is a key factor for patients with high or low risk of death

          • An NLR > 6.11 was associated with lower mortality in patients on corticosteroids

          • Corticosteroids did not reduce mortality in patients with an NLR ≤ 6.11 or with T2D

          Abstract

          While corticosteroid therapy is effective in the treatment of patients with severe COVID-19, a quantitative clinical parameter to identify such severity and which patients would respond well to corticosteroids has not been developed. Here, Cai et al. find that a simple blood test that measures the neutrophil-to-leukocyte ratio at admission discriminates high versus low mortality risk and a better response to corticosteroid therapy.

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          Most cited references36

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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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            Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

            Abstract Background Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death. Methods In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison. Results A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55). Conclusions In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.)
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              Dysregulation of immune response in patients with COVID-19 in Wuhan, China

              Abstract Background In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China. Methods Demographic and clinical data of all confirmed cases with COVID-19 on admission at Tongji Hospital from January 10 to February 12, 2020, were collected and analyzed. The data of laboratory examinations, including peripheral lymphocyte subsets, were analyzed and compared between severe and non-severe patients. Results Of the 452 patients with COVID-19 recruited, 286 were diagnosed as severe infection. The median age was 58 years and 235 were male. The most common symptoms were fever, shortness of breath, expectoration, fatigue, dry cough and myalgia. Severe cases tend to have lower lymphocytes counts, higher leukocytes counts and neutrophil-lymphocyte-ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most of severe cases demonstrated elevated levels of infection-related biomarkers and inflammatory cytokines. The number of T cells significantly decreased, and more hampered in severe cases. Both helper T cells and suppressor T cells in patients with COVID-19 were below normal levels, and lower level of helper T cells in severe group. The percentage of naïve helper T cells increased and memory helper T cells decreased in severe cases. Patients with COVID-19 also have lower level of regulatory T cells, and more obviously damaged in severe cases. Conclusions The novel coronavirus might mainly act on lymphocytes, especially T lymphocytes. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis and treatment of COVID-19.
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                Author and article information

                Journal
                Cell Metab
                Cell Metab
                Cell Metabolism
                Elsevier Inc.
                1550-4131
                1932-7420
                5 January 2021
                5 January 2021
                Affiliations
                [1 ]Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, China
                [2 ]School of Basic Medical Science, Wuhan University, Wuhan, China
                [3 ]Institute of Model Animal, Wuhan University, Wuhan, China
                [4 ]Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha 410000, China
                [5 ]The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, China
                [6 ]Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China
                [7 ]Department of Neurology, The First People’s Hospital of Jingmen affiliated to Hubei Minzu University, Jingmen 448000, China
                [8 ]Department of General Surgery, Ezhou Central Hospital, Ezhou 436000, China
                [9 ]Department of General Surgery, Huanggang Central Hospital, Huanggang 438000, China
                [10 ]Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China
                [11 ]Department of Hepatobiliary Surgery, The First Affiliated Hospital of Changjiang University, Jingzhou, China
                [12 ]Department of Hepatobiliary and Pancreatic Surgery, Xianning Central Hospital, Hubei Province, Xianning, China
                [13 ]Department of Hepatobiliary Surgery, Jingzhou Central Hospital, Jingzhou, China
                [14 ]Department of Gastroenterology, Wuhan Third Hospital and Tongren Hospital of Wuhan University, Wuhan, China
                [15 ]Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
                [16 ]Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
                [17 ]Department of Neonatology, Renmin Hospital of Wuhan University, Wuhan, China
                [18 ]Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
                [19 ]Centre for Clinic Pharmacology, The William Harvey Research Institute, Queen Mary University of London, London, UK
                [20 ]Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA 19004, USA
                [21 ]Departments of Anesthesiology, Physiology, and Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
                Author notes
                []Corresponding author
                [∗∗ ]Corresponding author
                [∗∗∗ ]Corresponding author
                [∗∗∗∗ ]Corresponding author
                [∗∗∗∗∗ ]Corresponding author
                [22]

                These authors contributed equally

                [23]

                Lead Contact

                Article
                S1550-4131(21)00002-4
                10.1016/j.cmet.2021.01.002
                7832609
                33421384
                9ef673e2-d5df-4e54-a350-1fdfa42dabab
                © 2021 Elsevier Inc.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 12 August 2020
                : 15 October 2020
                : 30 December 2020
                Categories
                Clinical and Translational Report

                Cell biology
                covid-19,corticosteroids,inflammatory status,neutrophil-to-lymphocyte ratio,mortality
                Cell biology
                covid-19, corticosteroids, inflammatory status, neutrophil-to-lymphocyte ratio, mortality

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