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      Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance

      review-article
      , MD a , b , c , , Prof, MD e , f , , Prof, MD g , , Prof, MD h , i , j , , Prof, MD k , , Prof, MD l , m , , Prof, MD n , , Prof, MD o , , MD p , , Prof, MD q , , MD r , , MD a , c , , Prof, PhD s , t , , Prof, MD v , , Prof, MD w , , Prof, MD x , y , z , , MD a , d , , Prof, MD u , aa , ab , , Prof, MD ac , , PhD ad , , Prof, MD u , ae , , Prof, MD a , b , c , af , ag , * , European Confederation of Medical Mycology, the International Society for Human Animal Mycology, the Asia Fungal Working Group, the INFOCUS LATAM/ISHAM Working Group, the ISHAM Pan Africa Mycology Working Group, the European Society for Clinical Microbiology, Infectious Diseases Fungal Infection Study Group, the ESCMID Study Group for Infections in Critically Ill Patients, the Interregional Association of Clinical Microbiology and Antimicrobial Chemotherapy, the Medical Mycology Society of Nigeria, the Medical Mycology Society of China Medicine Education Association, Infectious Diseases Working Party of the German Society for Haematology and Medical Oncology, Association of Medical Microbiology, Infectious Disease Canada
      The Lancet. Infectious Diseases
      Elsevier Ltd.

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          Abstract

          Severe acute respiratory syndrome coronavirus 2 causes direct damage to the airway epithelium, enabling aspergillus invasion. Reports of COVID-19-associated pulmonary aspergillosis have raised concerns about it worsening the disease course of COVID-19 and increasing mortality. Additionally, the first cases of COVID-19-associated pulmonary aspergillosis caused by azole-resistant aspergillus have been reported. This article constitutes a consensus statement on defining and managing COVID-19-associated pulmonary aspergillosis, prepared by experts and endorsed by medical mycology societies. COVID-19-associated pulmonary aspergillosis is proposed to be defined as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Recommended first-line therapy is either voriconazole or isavuconazole. If azole resistance is a concern, then liposomal amphotericin B is the drug of choice. Our aim is to provide definitions for clinical research and up-to-date recommendations for clinical management of the diagnosis and treatment of COVID-19-associated pulmonary aspergillosis.

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          Clinical Characteristics of Coronavirus Disease 2019 in China

          Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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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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              Virological assessment of hospitalized patients with COVID-2019

              Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.
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                Author and article information

                Journal
                Lancet Infect Dis
                Lancet Infect Dis
                The Lancet. Infectious Diseases
                Elsevier Ltd.
                1473-3099
                1474-4457
                14 December 2020
                14 December 2020
                Affiliations
                [a ]Faculty of Medicine, University of Cologne, Cologne, Germany
                [b ]Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany
                [c ]Department I of Internal Medicine, European Excellence Center for Medical Mycology (ECMM), University Hospital Cologne, Cologne, Germany
                [d ]Department of Radiology, University Hospital Cologne, Cologne, Germany
                [e ]Infectious Diseases Clinic, Department of Health Sciences, University of Genoa, Genoa, Italy
                [f ]Policlinico San Martino Hospital, Genoa, Italy
                [g ]Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
                [h ]Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, New South Wales Health Pathology, Sydney, NSW, Australia
                [i ]Department of Infectious Diseases, Westmead Hospital, Sydney, NSW, Australia
                [j ]School of Medicine, University of Sydney, Sydney, NSW, Australia
                [k ]Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
                [l ]Clinical and Translational Fungal-Working Group and Division of Infectious Diseases and Global Public Health, University of California San Diego, San Diego, CA, USA
                [m ]Section of Infectious Diseases and Tropical Medicine and Division of Pulmonology, Medical University of Graz, Graz, Austria
                [n ]Department of Clinical Mycology, Allergology and Immunology, North Western State Medical University, St Petersburg, Russia
                [o ]Institute of Hygiene and Medical Microbiology, ECMM, Medical University of Innsbruck, Innsbruck, Austria
                [p ]Department of Medical Microbiology and Parasitology, College of Medicine, University of Lagos, Lagos, Nigeria
                [q ]Division of Infectious Diseases, Department of Medicine, Department of Medical Microbiology, and Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, McGill University Health Centre, Montreal, QC, Canada
                [r ]Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
                [s ]Department of Pharmacy, ECMM, Center of Expertise in Mycology Radboudumc/CWZ, Radboud University Medical Center, Radboud University, Nijmegen, Netherlands
                [t ]Radboudumc Institute of Health Science, ECMM, Center of Expertise in Mycology Radboudumc/CWZ, Radboud University Medical Center, Radboud University, Nijmegen, Netherlands
                [u ]Department of Medical Microbiology, ECMM, Center of Expertise in Mycology Radboudumc/CWZ, Radboud University Medical Center, Radboud University, Nijmegen, Netherlands
                [v ]Université de Rennes, CHU de Rennes, EHESP, Institut de Recherche en Santé, Environnement et travail, Inserm UMR_S 1085, Rennes, France
                [w ]Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Duke University, Durham, NC, USA
                [x ]University of Texas Health San Antonio, San Antonio, TX, USA
                [y ]University Health, San Antonio, TX, USA
                [z ]South Texas Veterans Health Care System, San Antonio, TX, USA
                [aa ]Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, Netherlands
                [ab ]Bioprocess Engineering and Biotechnology Graduate Program, Federal University of Paraná, Curitiba, Brazil
                [ac ]Division of Infectious Diseases, McGovern Medical School, University of Texas, Houston, TX, USA
                [ad ]Mycology Reference Laboratory, Public Health Wales Microbiology Cardiff, Cardiff, UK
                [ae ]Center for Infectious Diseases Research, Diagnostics and Laboratory Surveillance, National Institute for Public Health and the Environment, Bilthoven, Netherlands
                [af ]Clinical Trials Centre Cologne, ZKS Köln, Cologne, Germany
                [ag ]German Center for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany
                Author notes
                [* ]Correspondence to: Prof Oliver A Cornely, Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany
                Article
                S1473-3099(20)30847-1
                10.1016/S1473-3099(20)30847-1
                7833078
                33333012
                f0ee6ee9-c12b-43ca-8915-824890a41564
                © 2020 Elsevier Ltd. All rights reserved.

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                Infectious disease & Microbiology

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