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      Efficacy of Corticosteroids in Patients with SARS, MERS and COVID-19: A Systematic Review and Meta-Analysis

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          Abstract

          (1) Background: The use of corticosteroids in critical coronavirus infections, including severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome (MERS), or Coronavirus disease 2019 (COVID-19), has been controversial. However, a meta-analysis on the efficacy of steroids in treating these coronavirus infections is lacking. (2) Purpose: We assessed a methodological criticism on the quality of previous published meta-analyses and the risk of misleading conclusions with important therapeutic consequences. We also examined the evidence of the efficacy of corticosteroids in reducing mortality in SARS, MERS and COVID-19. (3) Methods: PubMed, MEDLINE, Embase, and Web of Science were used to identify studies published until 25 April 2020, that reported associations between steroid use and mortality in treating SARS/MERS/COVID-19. Two investigators screened and extracted data independently. Searches were restricted to studies on humans, and articles that did not report the exact number of patients in each group or data on mortality were excluded. We calculated odds ratios (ORs) or hazard ratios (HRs) under the fixed- and random-effect model. (4) Results: Eight articles (4051 patients) were eligible for inclusion. Among these selected studies, 3416 patients were diagnosed with SARS, 360 patients with MERS, and 275 with COVID-19; 60.3% patients were administered steroids. The meta-analyses including all studies showed no differences overall in terms of mortality (OR 1.152, 95% CI 0.631–2.101 in the random effects model, p = 0.645). However, this conclusion might be biased, because, in some studies, the patients in the steroid group had more severe symptoms than those in the control group. In contrast, when the meta-analysis was performed restricting only to studies that used appropriate adjustment (e.g., time, disease severity), there was a significant difference between the two groups (HR 0.378, 95% CI 0.221–0.646 in the random effects model, p < 0.0001). Although there was no difference in mortality when steroids were used in severe cases, there was a difference among the group with more underlying diseases (OR 3.133, 95% CI 1.670–5.877, p < 0.001). (5) Conclusions: To our knowledge, this study is the first comprehensive systematic review and meta-analysis providing the most accurate evidence on the effect of steroids in coronavirus infections. If not contraindicated, and in the absence of side effects, the use of steroids should be considered in coronavirus infection including COVID-19.

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          Most cited references35

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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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              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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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                27 July 2020
                August 2020
                : 9
                : 8
                : 2392
                Affiliations
                [1 ]Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea; AZSAGM@ 123456yuhs.ac
                [2 ]Yonsei University College of Medicine, Seoul 03722, Korea; sj4068@ 123456naver.com (S.Y.); crossing96@ 123456yonsei.ac.kr (J.Y.K.); nzsarah61@ 123456gmail.com (S.R.)
                [3 ]College of Medicine, Gyeongsang National University, Jinju 52727, Korea; gwangh.jeong@ 123456gmail.com
                [4 ]Department of Pediatrics, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon 51353, Korea; 82agnes@ 123456hanmail.net
                [5 ]Department of Global Health and Population, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA; sunghwihong@ 123456gmail.com (S.H.H.); ramy.aboughayda@ 123456gmail.com (R.A.G.)
                [6 ]Department of Nephrology, Yonsei University Wonju College of Medicine, Wonju 26426, Korea; ripplesong@ 123456yonsei.ac.kr (J.S.K.); junyoung07@ 123456yonsei.ac.kr (J.Y.L.); kidney74@ 123456yonsei.ac.kr (J.W.Y.)
                [7 ]Department of Psychiatry, Yonsei University Wonju College of Medicine, Wonju 26426, Korea; jinh.lee95@ 123456yonsei.ac.kr
                [8 ]Department of Neuroscience, University of Padova, 35121 Padova, Italy; marco.solmi83@ 123456gmail.com
                [9 ]Research and development unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, Dr. Antoni Pujadas, 42, Sant Boi de Llobregat, 08830 Barcelona, Spain; a.koyanagi@ 123456pssjd.org (A.K.); louis.jacob.contacts@ 123456gmail.com (L.J.)
                [10 ]ICREA, Pg. Lluis Companys 23, 08010 Barcelona, Spain
                [11 ]Pain and Rehabilitation Centre, and Department of Health, Medicine and Caring Sciences, Linkoping University, SE-581 85 Linkoping, Sweden; elena.dragioti@ 123456liu.se
                [12 ]Faculty of Medicine, University of Versailles Saint-Quentin-en-Yvelines, 78180 Montigny-le-Bretonneux, France
                [13 ]Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; radua@ 123456clinic.cat
                [14 ]Mental Health Research Networking Center (CIBERSAM), 08036 Barcelona, Spain
                [15 ]Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK
                [16 ]Centre for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institutet, 11330 Stockholm, Sweden
                [17 ]The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge CB1 1PT, UK; lee.smith@ 123456anglia.ac.uk
                [18 ]School of Social Work, University of Southern California, Los Angeles, CA 90015, USA; hansoh@ 123456usc.edu
                [19 ]Department of Basic Sciences, Division of Histology and Immunology, Faculty of Medicine Tunis, Tunis El Manar University, Tunis 1068, Tunisia; kalttizaoui@ 123456gmail.com
                [20 ]Department of Pharmaceutical Sciences and Interdepartmental Research Center of Pharmacogenetics and Pharmacogenomics (CRIFF), University of Piemonte Orientale, 28100 Novara, Italy; sarah.cargnin@ 123456uniupo.it (S.C.); salvatore.terrazzino@ 123456uniupo.it (S.T.)
                [21 ]Division of Urology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
                [22 ]Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, 6020 Innsbruck, Austria; Andreas.Kronbichler@ 123456i-med.ac.at
                Author notes
                [* ]Correspondence: shinji@ 123456yuhs.ac ; Tel.: +82-2-2228-2050
                Author information
                https://orcid.org/0000-0002-1511-9587
                https://orcid.org/0000-0002-0594-6992
                https://orcid.org/0000-0003-4756-9440
                https://orcid.org/0000-0002-9781-4822
                https://orcid.org/0000-0001-8047-4190
                https://orcid.org/0000-0003-3689-5865
                https://orcid.org/0000-0003-4255-1831
                https://orcid.org/0000-0002-9565-5004
                https://orcid.org/0000-0001-9019-4125
                https://orcid.org/0000-0003-1071-1239
                https://orcid.org/0000-0003-1240-5438
                https://orcid.org/0000-0002-5340-9833
                https://orcid.org/0000-0001-6242-7817
                https://orcid.org/0000-0002-4909-1121
                https://orcid.org/0000-0002-5170-3983
                https://orcid.org/0000-0002-2945-2946
                https://orcid.org/0000-0003-2326-1820
                Article
                jcm-09-02392
                10.3390/jcm9082392
                7465945
                32726951
                693c0d0e-07d0-4bfd-ad40-3871ed5a1295
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 May 2020
                : 29 June 2020
                Categories
                Article

                corticosteroids,coronavirus,severe acute respiratory syndrome (sars),middle east respiratory syndrome (mers),coronavirus disease 2019 (covid-19)

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