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      Definition, diagnosis, and management of COVID-19-associated pulmonary mucormycosis: Delphi consensus statement from the Fungal Infection Study Forum and Academy of Pulmonary Sciences, India

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      , DM a , , Prof, DM a , , MD f , , MD b , , Prof, MD g , , Prof, DM a , , Prof, MD c , , Prof, MD i , , MD k , , Prof, DM l , , Prof, MD d , , DM j , , MD m , , Prof, MS o , , Prof, DM p , , MD q , , Prof, MD j , , Prof, DM r , , MD s , , Prof, MD e , , DM t , , MD n , , MD u , , MD v , , Prof, DM h , , Prof, MD g , , Prof, MD e , *
      The Lancet. Infectious Diseases
      Published by Elsevier Ltd.

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          Abstract

          COVID-19-associated pulmonary mucormycosis (CAPM) remains an underdiagnosed entity. Using a modified Delphi method, we have formulated a consensus statement for the diagnosis and management of CAPM. We selected 26 experts from various disciplines who are involved in managing CAPM. Three rounds of the Delphi process were held to reach consensus (≥70% agreement or disagreement) or dissensus. A consensus was achieved for 84 of the 89 statements. Pulmonary mucormycosis occurring within 3 months of COVID-19 diagnosis was labelled CAPM and classified further as proven, probable, and possible. We recommend flexible bronchoscopy to enable early diagnosis. The experts proposed definitions to categorise dual infections with aspergillosis and mucormycosis in patients with COVID-19. We recommend liposomal amphotericin B (5 mg/kg per day) and early surgery as central to the management of mucormycosis in patients with COVID-19. We recommend response assessment at 4–6 weeks using clinical and imaging parameters. Posaconazole or isavuconazole was recommended as maintenance therapy following initial response, but no consensus was reached for the duration of treatment. In patients with stable or progressive disease, the experts recommended salvage therapy with posaconazole or isavuconazole. CAPM is a rare but under-reported complication of COVID-19. Although we have proposed recommendations for defining, diagnosing, and managing CAPM, more extensive research is required.

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          Most cited references111

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          Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium

          Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the "One World One Guideline" initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.
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            A living WHO guideline on drugs for covid-19

            What is the role of drug interventions in the treatment and prevention of covid-19? The first version on this living guidance focuses on corticosteroids. It contains a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19, and a weak or conditional recommendation against systemic corticosteroids in patients with non-severe covid-19. Corticosteroids are inexpensive and are on the World Health Organisation list of essential medicines. this guideline was created This guideline reflects an innovative collaboration between the WHO and the MAGIC Evidence Ecosystem Foundation, driven by an urgent need for global collaboration to provide trustworthy and living covid-19 guidance. A standing international panel of content experts, patients, clinicians, and methodologists, free from relevant conflicts of interest, produce recommendations for clinical practice. The panel follows standards, methods, processes, and platforms for trustworthy guideline development using the GRADE approach. We apply an individual patient perspective while considering contextual factors (that is, resources, feasibility, acceptability, equity) for countries and healthcare systems. A living systematic review and network meta-analysis, supported by a prospective meta-analysis, with data from eight randomised trials (7184 participants) found that systemic corticosteroids probably reduce 28 day mortality in patients with critical covid-19 (moderate certainty evidence; 87 fewer deaths per 1000 patients (95% confidence interval 124 fewer to 41 fewer)), and also in those with severe disease (moderate certainty evidence; 67 fewer deaths per 1000 patients (100 fewer to 27 fewer)). In contrast, systemic corticosteroids may increase the risk of death in patients without severe covid-19 (low certainty evidence; absolute effect estimate 39 more per 1000 patients, (12 fewer to 107 more)). Systemic corticosteroids probably reduce the need for invasive mechanical ventilation, and harms are likely to be minor (indirect evidence). The panel made a strong recommendation for use of corticosteroids in severe and critical covid-19 because there is a lower risk of death among people treated with systemic corticosteroids (moderate certainty evidence), and they believe that all or almost all fully informed patients with severe and critical covid-19 would choose this treatment. In contrast, the panel concluded that patients with non-severe covid-19 would decline this treatment because they would be unlikely to benefit and may be harmed. Moreover, taking both a public health and a patient perspective, the panel warned that indiscriminate use of any therapy for covid-19 would potentially rapidly deplete global resources and deprive patients who may benefit from it most as potentially lifesaving therapy. This is a living guideline. Work is under way to evaluate other interventions. New recommendations will be published as updates to this guideline. This is version 1 of the living guideline, published on 4 September ( BMJ 2020;370:m3379) version 1. Updates will be labelled as version 2, 3 etc. When citing this article, please cite the version number. August 28 August 31
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              Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance

              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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                Author and article information

                Journal
                Lancet Infect Dis
                Lancet Infect Dis
                The Lancet. Infectious Diseases
                Published by Elsevier Ltd.
                1473-3099
                1474-4457
                4 April 2022
                4 April 2022
                Affiliations
                [a ]Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
                [b ]Department of Community Medicine and School of Public Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India
                [c ]Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
                [d ]Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India
                [e ]Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
                [f ]Department of Infectious Diseases, Sterling Hospital, Ahmedabad, India
                [g ]Department of Internal Medicine, Christian Medical College, Vellore, India
                [h ]Department of Pulmonary Medicine, Christian Medical College, Vellore, India
                [i ]Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
                [j ]Department of Pulmonary Medicine, All India Institute of Medical Sciences, New Delhi, India
                [k ]Department of Pulmonary Medicine, Institute of Pulmonology, Medical Research and Development, Mumbai, India
                [l ]Department of Pulmonary Medicine, Pandit Bhagwat Dayal Sharma Postgraduate Institute of Medical Sciences, Rohtak, India
                [m ]Department of Infectious Diseases, Apollo Hospitals, Chennai, India
                [n ]Department of Medical Microbiology, Apollo Hospitals, Chennai, India
                [o ]Department of Thoracic Surgery, Medanta Hospital, Gurgaon, India
                [p ]Department of Pulmonary Medicine, St John's Hospital, Bengaluru, India
                [q ]Department of Pulmonary Medicine, Apollo Hospitals, Bengaluru, India
                [r ]Department of Pulmonary Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
                [s ]Department of Pulmonary Medicine, City Clinic and Bhailal Amin General Hospital, Vadodara, India
                [t ]Department of Pulmonary Medicine, Army Hospital Research and Referral, New Delhi, India
                [u ]Department of Infectious Diseases, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, India
                [v ]Department of Infectious Diseases, Jupiter Hospital, Pune, India
                Author notes
                [* ]Correspondence to: Prof Arunaloke Chakrabarti, Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
                Article
                S1473-3099(22)00124-4
                10.1016/S1473-3099(22)00124-4
                8979562
                35390293
                f8af268b-7020-431e-bcfe-1863f3b403f9
                © 2022 Published by Elsevier Ltd.

                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.

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                Infectious disease & Microbiology
                Infectious disease & Microbiology

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