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      Inhaled prostacyclin analogues in COVID-19 associated acute respiratory distress syndrome: scientific rationale

      letter
      1 , , 2
      The Egyptian Heart Journal
      Springer Berlin Heidelberg
      ARDS, COVID-19, Epoprostenol, Prostacyclin

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          Abstract

          Background

          COVID-19 associated acute respiratory distress syndrome (CARDS) is a severe form of SARS CoV-2 infection and affects about 15–30% of hospitalized patients with a high mortality rate. Growing research and data suggest several available drugs with appropriate pharmacological effects to treat COVID-19.

          Main body

          Prostacyclin analogues are regiments for pulmonary artery hypertension. Prostacyclin analogues are expected to be beneficial in treating CARDS based on at least four rationales: (1) inhaled prostacyclin analogues improve oxygenation, V/ Q mismatch, and act as an ARDS therapy alternative; (2) it alleviates direct SARS-CoV-2-related coagulopathy; (3) increases nitric oxide production; and (4) possible anti-inflammatory effect. Prostacyclin analogues are available in oral, intravenous, and inhaled forms. The inhaled form has the advantage over other forms, such as parenteral administration risks. Previously, a meta-analysis demonstrated the beneficial effects of inhaled prostaglandins for ARDS treatment, such as improved PaO2/FiO2 and PaO2 along with reduced pulmonary artery pressure. Currently, two ongoing randomized controlled trials are evaluating inhaled epoprostenol (VPCOVID [NCT04452669]) and iloprost (ILOCOVID [NCT04445246]) for severe COVID-19 patients.

          Conclusions

          Inhaled prostacyclin could be considered in patients with refractory, life-threatening hypoxia despite standard management.

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          Most cited references28

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          Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

          Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated.
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            Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19)

            Background The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. Methods We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. Results The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy. Conclusion The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines. Electronic supplementary material The online version of this article (10.1007/s00134-020-06022-5) contains supplementary material, which is available to authorized users.
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              Interferon-gamma: an overview of signals, mechanisms and functions.

              Interferon-gamma (IFN-gamma) coordinates a diverse array of cellular programs through transcriptional regulation of immunologically relevant genes. This article reviews the current understanding of IFN-gamma ligand, receptor, signal transduction, and cellular effects with a focus on macrophage responses and to a lesser extent, responses from other cell types that influence macrophage function during infection. The current model for IFN-gamma signal transduction is discussed, as well as signal regulation and factors conferring signal specificity. Cellular effects of IFN-gamma are described, including up-regulation of pathogen recognition, antigen processing and presentation, the antiviral state, inhibition of cellular proliferation and effects on apoptosis, activation of microbicidal effector functions, immunomodulation, and leukocyte trafficking. In addition, integration of signaling and response with other cytokines and pathogen-associated molecular patterns, such as tumor necrosis factor-alpha, interleukin-4, type I IFNs, and lipopolysaccharide are discussed.
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                Author and article information

                Contributors
                eka.prasetya.budi-2017@fk.unair.ac.id
                kevin.luke-2016@fk.unair.ac.id
                Journal
                Egypt Heart J
                Egypt Heart J
                The Egyptian Heart Journal
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                1110-2608
                2090-911X
                16 September 2021
                16 September 2021
                December 2021
                : 73
                : 82
                Affiliations
                [1 ]GRID grid.473572.0, ISNI 0000 0004 0643 1506, Department of Cardiology and Vascular Medicine, Faculty of Medicine, , Universitas Airlangga – Dr. Soetomo General Hospital, ; Jl. Mayjen Prof. Dr. Moestopo No.6-8, Surabaya, 60286 Indonesia
                [2 ]GRID grid.440745.6, ISNI 0000 0001 0152 762X, Faculty of Medicine, , Universitas Airlangga, ; Jl. Mayjen Prof. Dr. Moestopo No.6-8, Surabaya, 60286 Indonesia
                Author information
                http://orcid.org/0000-0002-2681-7743
                http://orcid.org/0000-0003-2160-2927
                Article
                208
                10.1186/s43044-021-00208-y
                8443914
                34529182
                25c8d9c2-9e05-47f7-9078-70a8d3e50021
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 20 July 2021
                : 6 September 2021
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                © The Author(s) 2021

                ards,covid-19,epoprostenol,prostacyclin
                ards, covid-19, epoprostenol, prostacyclin

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